Patent Publication Number: US-2023151070-A1

Title: Vegfr-3-activating agents and oncolytic viruses and uses thereof for the treatment of cancer

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application claims the benefit of U.S. Provisional Patent Application No. 62/982,648, filed Feb. 27, 2020 and U.S. Provisional Patent Application No. 62/982,651, filed Feb. 27, 2020, each of which is incorporated by reference herein in its entirety. 
    
    
     REFERENCE TO SEQUENCE LISTING FILED ELECTRONICALLY 
     This application incorporates by reference a Sequence Listing submitted with this application as text file entitled “06923-307-228_SEQ_LISTING.txt” created on Feb. 25, 2021 and having a size of 365,513 bytes. 
     1. INTRODUCTION 
     In one aspect, provided herein are methods for treating cancer in a subject, comprising administering to a subject an oncolytic virus (e.g., an avian paramyxovirus (AMPV)) and a vascular endothelial growth factor (VEGF)-C agent, a VEGF-D agent, or another VEGF receptor (VEGFR)-3-activating agent. In another aspect, provided herein are oncolytic viruses (e.g. APMV) comprising a genome, wherein the genome comprises a transgene that comprises a nucleotide sequence encoding a VEGF-C agent, a VEGF-D agent or another VEGF receptor (VEGFR)-3-activating agent. In another aspect, provided herein are methods for treating cancer, comprising administering to a subject an oncolytic virus (e.g. APMV), wherein the oncolytic virus comprises a genome that comprises a transgene comprising a nucleotide sequence encoding a VEGF-C agent, a VEGF-D agent, or another VEGF receptor (VEGFR)-3-activating agent. 
     2. BACKGROUND 
     VEGF-C belongs to the VEGF family, which also includes VEGF-A, placental growth factor, VEGF-B, and VEGF-D. VEGF-C is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases (Joukov V, Kumar V, Sorsa T, Arighi E, Weich H, Saksela O, Alitalo K (1998) A recombinant mutant vascular endothelial growth factor-C that has lost vascular endothelial growth factor receptor-2 binding, activation, and vascular permeability activities J Biol Chem 273:6599-6602). VEGF-D is closely related to VEGF-C; VEGF-D is structurally and functionally similar to VEGF-C (Achen et al., 1998, PNAS 95(2): 548-553). Like VEGF-C, VEGF-D is a ligand for VEGFR-2 and VEGFR-3 (id.). Lymphangiogenesis—the growth of lymphatic vessels from pre-existing ones—occurs mainly in response to VEGF-C and VEGF-D induced VEGFR3 activation (Jeltsch Metal. (1997) Hyperplasia of lymphatic vessels in VEGF-C transgenic mice Science 276:1423-1425; Karkkainen M J et al. (2004) Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins Nat Immunol 5:74-80 doi:10.1038/ni1013). VEGF-C is synthesized as a precursor in which the central VEGF homology domain (VHD) is flanked by N- and C-terminal propeptides. VEGF-C precursor undergoes proteolytic processing that generates an intermediately processed form which selectively binds VEGFR-3 and fully processed (mature) form that has increased affinity for VEGFR-3 and also binds the major angiogenic receptor VEGFR2 (Bui H M et al. (2016) Proteolytic activation defines distinct lymphangiogenic mechanisms for VEGFC and VEGFD J Clin Invest 126:2167-2180 doi:10.1172/JCI83967; Jeltsch M et al. (2014) CCBE1 enhances lymphangiogenesis via A disintegrin and metalloprotease with thrombospondin motifs-3-mediated vascular endothelial growth factor-C activation Circulation 129:1962-1971 doi:10.1161/CIRCULATIONAHA.113.002779; Joukov et al. 1997; Le Guen L et al. (2014) Ccbel regulates Vegfc-mediated induction of Vegfr3 signaling during embryonic lymphangiogenesis Development 141:1239-1249 doi:10.1242/dev.100495; Roukens M G et al. (2015) Functional Dissection of the CCBE1 Protein: A Crucial Requirement for the Collagen Repeat Domain Circ Res 116:1660-1669 doi:10.1161/CIRCRESAHA.116.304949). VEGF-D also undergoes proteolytic processing, which is necessary for producing active, mature form of VEGF-D. However, proteolytic cleavage of VEGF-D involves different proteases than that of VEGF-C (McColl B K et al. (2003) Plasmin activates the lymphangiogenic growth factors VEGF-C and VEGF-D J Exp Med 198:863-868 doi:10.1084/jem.20030361). 
     VEGFR-3 is primarily expressed by lymphatic endothelial cells. It is phosphorylated following activation with its ligands VEGF-C and VEGF-D, leading to downstream signaling events. In particular, VEGF-C-induced VEGFR-3 activation leads to phosphorylation of the serine/threonine kinases AKT and ERK, which promote lymphatic endothelial cell (LEC) proliferation, migration and survival (Gibot L, Galbraith T, Kloos B, Das S, Lacroix D A, Auger F A, Skobe M (2016) Cell-based approach for 3D reconstruction of lymphatic capillaries in vitro reveals distinct functions of HGF and VEGF-C in lymphangiogenesis Biomaterials 78:129-139 doi:10.1016/j.biomaterials.2015.11.027; Makinen T et al. (2001) Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF-C/D receptor VEGFR-3 EMBO J 20:4762-4773 doi:10.1093/emboj/20.17.4762; Salameh A, Galvagni F, Bardelli M, Bussolino F, Oliviero S (2005) Direct recruitment of CRK and GRB2 to VEGFR-3 induces proliferation, migration, and survival of endothelial cells through the activation of ERK, AKT, and JNK pathways Blood 106:3423-3431 doi:10.1182/blood-2005-04-1388). 
     VEGF-C is a key lymphangiogenesis factor. Thus far, VEGF-C has been considered as a therapeutic modality for lymphedema patients, to promote regeneration of new lymphatic vessels (Baker, A., Kim, H., Semple, J. L., Dumont, D., Shoichet, M., Tobbia, D., and Johnston, M. (2010). Experimental assessment of pro-lymphangiogenic growth factors in the treatment of post-surgical lymphedema following lymphadenectomy. Breast Cancer Res 12, R70; Szuba, A., Skobe, M., Karkkainen, M. J., Shin, W. S., Beynet, D. P., Rockson, N. B., Dakhil, N., Spilman, S., Goris, M. L., Strauss, H. W., et al. (2002). Therapeutic lymphangiogenesis with human recombinant VEGF-C. FASEB J 16, 1985-1987.; Visuri, M. T., Honkonen, K. M., Hartiala, P., Tervala, T. V., Halonen, P. J., Junkkari, H., Knuutinen, N., Yla-Herttuala, S., Alitalo, K. K., and Saarikko, A. M. (2015). VEGF-C and VEGF-C156S in the pro-lymphangiogenic growth factor therapy of lymphedema: a large animal study. Angiogenesis 18, 313-326.; Yoon, Y. S., Murayama, T., Gravereaux, E., Tkebuchava, T., Silver, M., Curry, C., Wecker, A., Kirchmair, R., Hu, C. S., Kearney, M., et al. (2003). VEGF-C gene therapy augments postnatal lymphangiogenesis and ameliorates secondary lymphedema. J Clin Invest 111, 717-725.). Inhibition of VEGF-C or its receptor VEGFR-3 has been evaluated as a therapeutic approach for preventing and inhibiting metastasis, because VEGF-C mediated induction of lymphangiogenesis promotes metastasis in many cancer types (Burton et al., 2008; Das et al., 2010; Lin et al., 2005; Roberts et al., 2006; Saif et al., 2016; Skobe et al., 2001; Stacker et al., 2014). 
     Cancer is a second leading cause of death worldwide, the most common cancers being lung cancer, breast cancer, colorectal cancer, prostate cancer, skin cancer and stomach cancer. See, World Health Organization Fact Sheet Cancer, September 2018, available at: https://www.who.int/news-room/fact-sheets/detail/cancer (accessed Feb. 11, 2020). Existing therapies to treat cancer are often limited in their application due to variable efficacy between patients and high toxicity. See Voon and Kong, 2011, “Tumour Genetics and Genomics to Personalise Cancer Treatment”, Ann Acad Med Singapore 2011; 40:362-8. Thus, effective therapies for treating cancer are needed. 
     3. SUMMARY 
     In one aspect, provided herein are recombinant nucleic acid sequences comprising a nucleotide sequence of an oncolytic virus genome and a transgene, wherein the transgene comprises a nucleotide sequence encoding a nucleotide sequence encoding a VEGFR-3 activating agent. See section 5.2 and 5.3.2 for examples of VEGFR-3 activating agents. In another aspect, provided herein are recombinant nucleic acid sequences comprising a nucleotide sequence of an oncolytic virus genome and a transgene, wherein the transgene comprises a nucleotide sequence encoding vascular endothelial growth factor (VEGF)-C or VEGF-D. See sections 5.2 and 5.3.2 for examples of VEGF-C and VEGF-D sequences. In certain embodiments, the nucleotide sequence encoding VEGF-C comprises the sequence set forth in any one of SEQ ID NOs: 1-18, 29-40, 49, or 50. In some embodiments, the VEGF-C comprises the amino acid sequence set forth in any one of SEQ ID NOs: 19-24, 41-46, 51, or 52. In certain embodiments, the nucleotide sequence encoding VEGF-D comprises the sequence set forth in any one of SEQ ID NOs: 96-98. In some embodiments, the VEGF-D comprises the amino acid sequence set forth in any one of SEQ ID NO: 99-104. See, e.g., Section 5.1 and 5.3 for examples of oncolytic viruses. In one embodiment, the oncolytic virus is a parvovirus, a myxoma virus, a Newcastle disease virus, an APMV-2, an APMV-3, an APMV-4, an APMV-5, an APMV-6, an APMV-7, an APMV-8, or an APMV-9, a reovirus, or Seneca valley virus. In another embodiment, the oncolytic virus is a genetically engineered influenza virus, measles virus, poliovirus, vaccinia virus, poxvirus, picornavirus, alphavirus, retrovirus, rhabdovirus, reovirus, adenovirus, herpes simplex virus, or vesicular stomatitis virus. 
     In another aspect, provided herein are recombinant nucleic acid sequences comprising a nucleotide sequence of an avian paramyxovirus (APMV) genome and a transgene, wherein the transgene comprises a nucleotide sequence encoding a VEGFR-3 activating agent. In another aspect, provided herein is a recombinant nucleic acid sequence comprising a nucleotide sequence of an avian paramyxovirus (APMV) genome and a transgene, wherein the transgene comprises a nucleotide sequence encoding vascular endothelial growth factor (VEGF)-C or VEGF-D. See sections 5.2 and 5.3.2 for examples of VEGF-C and VEGF-D sequences. In a specific embodiment, the genome comprises a transcription unit encoding a nucleocapsid (N) protein, a transcription unit encoding a phosphoprotein (P), a transcription unit encoding a matrix (M) protein, a transcription unit encoding a fusion (F) protein, a transcription unit encoding a hemagglutinin-neuraminidase (HN), and a transcription unit encoding a large polymerase (L) protein. In another specific embodiment, the transgene is incorporated between the M and P transcription units or between the HN and L transcription units. In a particular embodiment, the APMV is Newcastle disease virus (NDV). In another embodiment, the APMV is NDV and the F protein of the NDV contains a leucine to alanine substitution at amino acid residue 289. In a specific embodiment, the APMV is NDV and the transgene comprises the nucleotide sequence of SEQ ID NO: 87. In another embodiment, the APMV is APMV serotype 4 (APMV-4). In a specific embodiment, APMV is AMPV-4 and the transgene comprises the nucleotide sequence of SEQ ID NO: 89. In certain embodiments, the nucleotide sequence encoding VEGF-C comprises the sequence set forth in any one of SEQ ID NOs: 1-18, 29-40, 49, or 50. In a specific embodiment, the nucleotide sequence encoding VEGF-C comprises the sequence set forth in any one of SEQ ID Nos: 29-40. In some embodiments, the VEGF-C comprises the amino acid sequence set forth in any one of SEQ ID NOs: 19-24, 41-46, 51, or 52. In a specific embodiment, the VEGF-C comprises the amino acid sequence set forth in any one of SEQ ID Nos: 41-46. In certain embodiments, the nucleotide sequence encoding VEGF-D comprises the sequence set forth in any one of SEQ ID NOs: 96-98. In some embodiments, the VEGF-D comprises the amino acid sequence set forth in any one of SEQ ID NOs: 99-104. In a specific embodiment, provided herein is a recombinant nucleic acid sequence comprising the nucleotide sequence of SEQ ID NO: 88 or 90. 
     In another aspect, provided herein is a recombinant oncolytic virus comprising a genome that comprises a transgene, wherein the transgene comprises a nucleotide sequence encoding a VEGFR-3 activating agent. In another aspect, provided herein is a recombinant oncolytic virus comprising a genome that comprises a transgene, wherein the transgene comprises a nucleotide sequence encoding VEGF-C or VEGF-D. See, e.g., Section 5.1 and 5.3 for examples of oncolytic viruses. In one embodiment, the oncolytic virus is a parvovirus, a myxoma virus, a Newcastle disease virus, an APMV-2, an APMV-3, an APMV-4, an APMV-5, an APMV-6, an APMV-7, an APMV-8, or an APMV-9, a reovirus, or Seneca valley virus. In another embodiment, the oncolytic virus is a genetically engineered influenza virus, measles virus, poliovirus, vaccinia virus, poxvirus, picornavirus, alphavirus, retrovirus, rhabdovirus, reovirus, adenovirus, herpes simplex virus, or vesicular stomatitis virus. In some embodiments, the nucleotide sequence encoding VEGF-C comprises the sequence set forth in any one of SEQ ID NOs: 1-18, 29-40, 49, or 50. In a specific embodiment, the VEGF-C comprises the amino acid sequence set forth in any one of SEQ ID Nos: 29-40. In certain embodiments, the VEGF-C comprises the amino acid sequence set forth in any one of SEQ ID NOs: 19-24, 41-46, 51, or 52. In a specific embodiment, the VEGF-C comprises the amino acid sequence set forth in any one of SEQ ID Nos: 41-46. In some embodiments, the nucleotide sequence encoding VEGF-D comprises the sequence set forth in any one of SEQ ID NOs: 96-98. In certain embodiments, the VEGF-D comprises the amino acid sequence set forth in any one of SEQ ID NOs: 99-104. 
     In another aspect, provided herein is a recombinant avian paramyxovirus (APMV) comprising a packaged genome, wherein the packaged genome comprises a transgene that comprises a nucleotide sequence encoding VEGF-C or VEGF-D. In a specific embodiment, the genome comprises a transcription unit encoding a nucleocapsid (N) protein, a transcription unit encoding a phosphoprotein (P), a transcription unit encoding a matrix (M) protein, a transcription unit encoding a fusion (F) protein, a transcription unit encoding a hemagglutinin-neuraminidase (HN), and a transcription unit encoding a large polymerase (L) protein. In another specific embodiment, the transgene is incorporated between the M and P transcription units or between the HN and L transcription units. In a particular embodiment, the APMV is Newcastle disease virus (NDV). In another embodiment, the APMV is NDV and the F protein of the NDV contains a leucine to alanine substitution at amino acid residue 289. In a specific embodiment, the APMV is NDV and the transgene comprises the nucleotide sequence of SEQ ID NO: 87. In another embodiment, the APMV is APMV serotype 4 (APMV-4). In a specific embodiment, APMV is AMPV-4 and the transgene comprises the nucleotide sequence of SEQ ID NO: 89. In certain embodiments, the nucleotide sequence encoding VEGF-C comprises the sequence set forth in any one of SEQ ID Nos: 1-18, 29-40, 49, or 50. In a specific embodiment, the VEGF-C comprises the amino acid sequence set forth in any one of SEQ ID Nos: 29-40. In some embodiments, the VEGF-C comprises the amino acid sequence set forth in any one of SEQ ID NOs: 19-24, 41-46, 51, or 52. In a specific embodiment, the VEGF-C comprises the amino acid sequence set forth in any one of SEQ ID Nos: 41-46. In certain embodiments, the nucleotide sequence encoding VEGF-D comprises the sequence set forth in any one of SEQ ID NOs: 96-98. In some embodiments, the VEGF-D comprises the amino acid sequence set forth in any one of SEQ ID NO: 99-104. In a specific embodiment, provided herein is a recombinant nucleic acid sequence comprising the nucleotide sequence of SEQ ID NO: 88 or 90. 
     In another aspect, provided herein are pharmaceutical compositions comprising an oncolytic virus described herein (e.g., an APMV described herein) in a pharmaceutically acceptable carrier or excipient. In certain embodiments, a pharmaceutical composition contains 10 6  to 10 10  plaque forming units (pfu) of an oncolytic virus described herein. In a specific embodiment, provided herein is a pharmaceutical composition comprising a recombinant APMV described herein in a pharmaceutically acceptable carrier or excipient. 
     In another aspect, provided herein are methods for treating cancer comprising administering an oncolytic virus described herein or a composition thereof to a subject. In a specific embodiment, provided herein is a method for treating cancer, comprising administering a dose of a pharmaceutical composition described herein to a subject. In some embodiments, a therapeutically-effective dose of the pharmaceutical composition is administered. In some embodiments, the oncolytic virus or pharmaceutical composition is administered to the subject intratumorally. In certain embodiments, a dose of a pharmaceutical composition contains 10 6  to 10 10  plaque forming units (pfu) of an oncolytic virus described herein. In specific embodiments, the cancer treated in accordance with the methods described herein is melanoma, lung carcinoma, colon carcinoma, glioblastoma, head and neck cancer, pancreatic cancer, hepatocellular carcinoma, ovarian cancer, squamous cell cancer, basal cell cancer, bladder cancer, prostate cancer, B-cell lymphoma, T-cell lymphoma, gastric cancer, colorectal cancer or breast cancer. In certain embodiments, the cancer treated in accordance with the methods described herein is metastatic. In some embodiments, the cancer treated in accordance with the methods described herein is unresectable. In a specific embodiment, the subject treated in accordance with the methods described herein is human. 
     In another aspect, provided herein are methods for treating cancer, comprising administering to a subject an oncolytic virus or a composition thereof, and administering a VEGFR3 activating agent or a composition thereof. The activating agent may be in the same or different compositions as the oncolytic virus. See section 5.2 and 5.3.2 for examples of VEGFR-3-activating agents. In another aspect, provided are methods for treating cancer, comprising administering to a subject an oncolytic virus and administering to the subject VEGF-C or VEGF-D. In some embodiments, the oncolytic virus and the VEGF-C or VEGF-D are in the same composition. In other embodiments, the oncolytic virus and the VEGF-C or VEGF-D are in different compositions. The different compositions may be administered to the subject concurrently or at different times. The oncolytic virus may be administered to the subject intratumorally and the VEGF-C or VEGF-D may be administered to the subject intratumorally, intramuscularly, intranasally, intradermally or subcutaneously. In a specific embodiment, provided herein are methods for treating cancer, comprising administering intratumorally to a subject a dose of a first pharmaceutical composition comprising an oncolytic virus and administering to the subject a dose of a second pharmaceutical composition comprising VEGF-C or VEGF-D. In some embodiments, a therapeutically-effective dose of the first pharmaceutical composition, a therapeutically-effective dose the second pharmaceutical composition, or both is administered to the subject. In certain embodiments, the VEGF-C is encoded by a nucleotide sequence comprising the sequence set forth in any one of SEQ ID NOs: 1-18, 29-40, 49, or 50. In a specific embodiment, the VEGF-C comprises the amino acid sequence set forth in any one of SEQ ID Nos: 29-40. In some embodiments, the VEGF-C comprises the amino acid sequence set forth in any one of SEQ ID NOs: 19-24, 41-46, 51, or 52. In a specific embodiment, the VEGF-C comprises the amino acid sequence set forth in any one of SEQ ID Nos: 41-46. In certain embodiments, the VEGF-D is encoded by a nucleotide sequence comprising the sequence set forth in any one of SEQ ID NOs: 96-98. In some embodiments, the VEGF-D comprises the amino acid sequence set forth in any one of SEQ ID NOs: 99-104. In certain embodiments, the second pharmaceutical composition is administered to the subject intratumorally, intramuscularly, intranasally, intradermally, or subcutaneously. In some embodiments, the subject treated in accordance with the methods described herein is not administered an antigen (e.g., a cancer antigen). In certain embodiments, a dose of the first pharmaceutical composition contains 10 6  to 10 10  pfu of the virus. See, e.g., Section 5.1 and 5.3 for examples of oncolytic viruses. In one embodiment, the oncolytic virus is a parvovirus, a myxoma virus, a Newcastle disease virus, an APMV-2, an APMV-3, an APMV-4, an APMV-5, an APMV-6, an APMV-7, an APMV-8, or an APMV-9, a reovirus, or Seneca valley virus. In another embodiment, the oncolytic virus is a genetically engineered influenza virus, measles virus, poliovirus, vaccinia virus, poxvirus, picornavirus, alphavirus, retrovirus, rhabdovirus, reovirus, adenovirus, herpes simplex virus, or vesicular stomatitis virus. In some embodiments, the oncolytic virus is an APMV (e.g., APMV-4 or Newcastle disease virus). In specific embodiments, the cancer treated in accordance with the methods described herein is melanoma, lung carcinoma, colon carcinoma, glioblastoma, head and neck cancer, pancreatic cancer, hepatocellular carcinoma, ovarian cancer, squamous cell cancer, basal cell cancer, bladder cancer, prostate cancer, B-cell lymphoma, T-cell lymphoma, gastric cancer, colorectal cancer or breast cancer. In certain embodiments, the cancer treated in accordance with the methods described herein is metastatic. In some embodiments, the cancer treated in accordance with the methods described herein is unresectable. In a specific embodiment, the subject treated in accordance with the methods described herein is human. 
     In another aspect, provided are methods for treating cancer, comprising administering to a subject an oncolytic virus and administering to the subject a nucleic acid sequence comprising a nucleotide sequence encoding VEGF-C or VEGF-D. In some embodiments, the oncolytic virus and the nucleotide sequence are in the same composition. In other embodiments, the oncolytic virus and the nucleotide sequence are in different compositions. The different compositions may be administered to the subject concurrently or at different times. The oncolytic virus may be administered to the subject intratumorally and the nucleotide sequence may be administered to the subject intratumorally, intramuscularly, intranasally, intradermally or subcutaneously. In a specific embodiment, provided herein is a method for treating cancer, comprising administering intratumorally to a subject a dose of a first pharmaceutical composition comprising an oncolytic virus and administering to the subject a dose of a second pharmaceutical composition a nucleic acid sequence comprising a nucleotide sequence encoding VEGF-C or VEGF-D. In some embodiments, a therapeutically-effective dose of the first pharmaceutical composition, a therapeutically-effective dose of the second pharmaceutical composition, or both is administered to the subject. In certain embodiments, the nucleotide sequence encoding VEGF-C comprises the sequence set forth in any one of SEQ ID NOs: 1-18, 29-40, 49, or 50. In a specific embodiment, the VEGF-C comprises the amino acid sequence set forth in any one of SEQ ID Nos: 29-40. In some embodiments, the VEGF-C comprises the amino acid sequence set forth in any one of SEQ ID NOs: 19-24, 41-46, 51, or 52. In a specific embodiment, the VEGF-C comprises the amino acid sequence set forth in any one of SEQ ID Nos: 41-46. In certain embodiments, the nucleotide sequence encoding VEGF-D comprises the sequence set forth in any one of SEQ ID NOs: 96-98. In some embodiments, the VEGF-D comprises the amino acid sequence set forth in any one of SEQ ID NO: 99-104. In certain embodiments, the second pharmaceutical composition is administered to the subject intratumorally, intramuscularly, intranasally, intradermally or subcutaneously. In some embodiments, the subject treated in accordance with the methods described herein is not administered an antigen (e.g., a cancer antigen). In certain embodiments, a dose of the first pharmaceutical composition contains 10 6  to 10 10  pfu of the virus. See, e.g., Section 5.1 and 5.3 for examples of oncolytic viruses. In one embodiment, the oncolytic virus is a parvovirus, a myxoma virus, a Newcastle disease virus, an APMV-2, an APMV-3, an APMV-4, an APMV-5, an APMV-6, an APMV-7, an APMV-8, or an APMV-9, a reovirus, or Seneca valley virus. In another embodiment, the oncolytic virus is a genetically engineered influenza virus, measles virus, poliovirus, vaccinia virus, poxvirus, picornavirus, alphavirus, retrovirus, rhabdovirus, reovirus, adenovirus, herpes simplex virus, or vesicular stomatitis virus. In some embodiments, the oncolytic virus is an APMV (e.g., APMV-4 or Newcastle disease virus). In specific embodiments, the cancer treated in accordance with the methods described herein is melanoma, lung carcinoma, colon carcinoma, glioblastoma, head and neck cancer, pancreatic cancer, hepatocellular carcinoma, ovarian cancer, squamous cell cancer, basal cell cancer, bladder cancer, prostate cancer, B-cell lymphoma, T-cell lymphoma, gastric cancer, colorectal cancer or breast cancer. In certain embodiments, the cancer treated in accordance with the methods described herein is metastatic. In some embodiments, the cancer treated in accordance with the methods described herein is unresectable. In a specific embodiment, the subject treated in accordance with the methods described herein is human. 
     In a specific embodiment, provided herein is a method for treating cancer, comprising administering a therapeutically effective dose of the pharmaceutical composition described herein to a subject (e.g., human subject) in need thereof. In certain embodiments, the pharmaceutical composition is administered to the subject intratumorally. In some embodiments, the therapeutically effective dose comprises 10 6  to 10 10  pfu of the virus. In certain embodiments, the cancer treated is melanoma, lung carcinoma, colon carcinoma, glioblastoma, head and neck cancer, pancreatic cancer, hepatocellular carcinoma, ovarian cancer, squamous cell cancer, basal cell cancer, bladder cancer, prostate cancer, B-cell lymphoma, T-cell lymphoma, or breast cancer. In some embodiments, the cancer is metastatic. In certain embodiments, the cancer is unresectable. 
     In another specific embodiment, provided herein is a method for treating cancer, comprising administering (e.g, intratumorally administering) to a subject (e.g., a human subject) in need thereof a therapeutically effective dose of a first pharmaceutical composition comprising an oncolytic virus (e.g., an APMV, such as APMV-1 or APMV-4) and administering to the subject a therapeutically effective dose of a second pharmaceutical composition comprising VEGF-C or VEGF-D. In another specific embodiment, provided herein is a method for treating cancer, comprising administering (e.g., intratumorally administering) to a subject (e.g., a human subject) in need thereof a dose of a first pharmaceutical composition comprising an oncolytic virus (e.g., an APMV, such as APMV-1 or APMV-4) and administering to the subject a dose of a second pharmaceutical composition comprising a nucleotide sequence encoding VEGF-C or VEGF-D. In certain embodiments, the nucleotide sequence encodes VEGF-C, and the nucleotide sequence that encodes VEGF-C comprises the sequence set forth in any one of SEQ ID NOs: 1-18, 29-40, 49, or 50. In some embodiments, the VEGF-C comprises the amino acid sequence set forth in any one of SEQ ID NOs: 19-24, 41-46, 51, or 52. In some embodiments, the nucleotide sequence encodes VEGF-D and the nucleotide sequence that encodes VEGF-D comprises the sequence set forth in any one of SEQ ID NOs: 96-98. In certain embodiments, the VEGF-D comprises the amino acid sequence set forth in any one of SEQ ID NOs: 99-104. In some embodiments, the second pharmaceutical composition is administered to the subject intratumorally, intramuscularly, intranasally, intradermally, or subcutaneously. In some embodiments, the subject is not administered an antigen. In certain embodiments, the therapeutically effective dose of the first pharmaceutical composition contains 10 6  to 10 10  pfu of the virus. In specific embodiments, the therapeutically effective dose of the VEGF-C agent or VEGF-D agent is 1 mg/kg to 100 mg/kg if the agent is proteinaceous. In certain embodiments, the cancer treated is melanoma, lung carcinoma, colon carcinoma, glioblastoma, head and neck cancer, pancreatic cancer, hepatocellular carcinoma, ovarian cancer, squamous cell cancer, basal cell cancer, bladder cancer, prostate cancer, B-cell lymphoma, T-cell lymphoma, or breast cancer. In some embodiments, the cancer is metastatic. In certain embodiments, the cancer is unresectable. 
     3.1 Terminology 
     As used herein, the term “about” or “approximately” when used in conjunction with a number refers to any number within 1, 5 or 10% of the referenced number, including the referenced number. 
     As used herein, the terms “antibody” and “antibodies” refer to molecules that contain an antigen-binding site, e.g., immunoglobulins. Antibodies include, but are not limited to, monoclonal antibodies, bispecific antibodies, multispecific antibodies, human antibodies, humanized antibodies, synthetic antibodies, chimeric antibodies, polyclonal antibodies, single domain antibodies, camelized antibodies, single-chain Fvs (scFv), single chain antibodies, Fab fragments, F(ab′) fragments, disulfide-linked bispecific Fvs (sdFv), intrabodies, and anti-idiotypic (anti-Id) antibodies (including, e.g., anti-Id and anti-anti-Id antibodies to antibodies), and epitope-binding fragments of any of the above. In particular, antibodies include immunoglobulin molecules and immunologically active fragments of immunoglobulin molecules. Immunoglobulin molecules can be of any type (e.g., IgG, IgE, IgM, IgD, IgA and IgY), class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2) or subclass. In a specific embodiment, an antibody is a human or humanized antibody. In another specific embodiment, an antibody is a monoclonal antibody or scFv. In certain embodiments, an antibody is a human or humanized monoclonal antibody or scFv. In other specific embodiments, the antibody is a bispecific antibody. 
     As used herein, the term “elderly human” refers to a human 65 years or older. 
     As used herein, the term “fragment” in the context of a nucleotide sequence refers to a nucleotide sequence comprising a nucleic acid sequence of at least 5 contiguous nucleic acid bases, at least 10 contiguous nucleic acid bases, at least 15 contiguous nucleic acid bases, at least 20 contiguous nucleic acid bases, at least 25 contiguous nucleic acid bases, at least 40 contiguous nucleic acid bases, at least 50 contiguous nucleic acid bases, at least 60 contiguous nucleic acid bases, at least 70 contiguous nucleic acid bases, at least 80 contiguous nucleic acid bases, at least 90 contiguous nucleic acid bases, at least 100 contiguous nucleic acid bases, at least 125 contiguous nucleic acid bases, at least 150 contiguous nucleic acid bases, at least 175 contiguous nucleic acid bases, at least 200 contiguous nucleic acid bases, or at least 250 contiguous nucleic acid bases of the nucleotide sequence of the gene of interest or longer nucleic acid sequence of interest. The nucleic acid may be RNA, DNA, or a chemically modified variant thereof. 
     As used herein, the term “fragment” is the context of a fragment of a proteinaceous agent (e.g., a protein or polypeptide) refers to a fragment that is composed of 8 or more contiguous amino acids, 10 or more contiguous amino acids, 15 or more contiguous amino acids, 20 or more contiguous amino acids, 25 or more contiguous amino acids, 50 or more contiguous amino acids, 75 or more contiguous amino acids, 100 or more contiguous amino acids, 150 or more contiguous amino acids, 200 or more contiguous amino acids, 10 to 150 contiguous amino acids, 10 to 200 contiguous amino acids, 10 to 250 contiguous amino acids, 10 to 300 contiguous amino acids, 50 to 100 contiguous amino acids, 50 to 150 contiguous amino acids, 50 to 200 contiguous amino acids, 50 to 250 contiguous amino acids or 50 to 300 contiguous amino acids of a proteinaceous agent. 
     As used herein, the term “heterologous” in the context of a virus to refers an entity not found in nature to be associated with (e.g., encoded by, expressed by the genome of, or both) a naturally occurring virus (e.g., a naturally occurring APMV). In a specific embodiment, a heterologous sequence in the context of a virus encodes a protein that is not found associated with naturally occurring virus (e.g., a naturally occurring APMV). 
     As used herein, the term “heterologous” in the context of a sequence to refers a sequence not found in nature to be associated with or part of a naturally occurring sequence. 
     As used herein, the term “human adult” refers to a human that is 18 years or older. 
     As used herein, the term “human child” refers to a human that is 1 year to 18 years old. 
     As used herein, the term “human infant” refers to a newborn to 1-year-old year human. 
     As used herein, the term “human toddler” refers to a human that is 1 year to 3 years old. 
     As used herein, the term “in combination” in the context of the administration of (a) therapy(ies) to a subject, refers to the use of more than one therapy. The use of the term “in combination” does not restrict the order in which therapies are administered to a subject. A first therapy can be administered prior to (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks before), concomitantly with, or subsequent to (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks after) the administration of a second therapy to a subject. For example, a recombinant APMV described herein may be administered prior to (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks before) concomitantly with, or subsequent to (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks after) the administration of another therapy. 
     As used herein, the phrases “interferon-deficient systems,” “interferon-deficient substrates,” “IFN deficient systems” or “IFN-deficient substrates” refer to systems, e.g., cells, cell lines and animals, such as mice, chickens, turkeys, rabbits, rats, horses etc., which do not produce one, two or more types of IFN, or do not produce any type of IFN, or produce low levels of one, two or more types of IFN, or produce low levels of any IFN (i.e., a reduction in any IFN expression of 5-10%, 10-20%, 20-30%, 30-40%, 40-50%, 50-60%, 60-70%, 70-80%, 80-90% or more when compared to IFN-competent systems under the same conditions), do not respond or respond less efficiently to one, two or more types of IFN, or do not respond to any type of IFN, have a delayed response to one, two or more types of IFN, and/or are deficient in the activity of antiviral genes induced by one, two or more types of IFN, or induced by any type of IFN. 
     As used herein, the phrase “multiplicity of infection” or “MOI” has its customary meaning. Generally, MOI is the average number of virus per infected cell. The MOI is generally determined by dividing the number of virus added (ml added×Pfu) by the number of cells added (ml added×cells/ml). 
     As used herein, the term “native” in the context of proteins or polypeptides refers to any naturally occurring amino acid sequence, including immature or precursor and mature forms of a protein. In a specific embodiment, the native polypeptide is a human protein or polypeptide. 
     As used herein, the term “naturally occurring” in the context of a virus (e.g., an APMV) refers to a virus (e.g., an APMV) found in nature, which is not modified by the hand of man. In other words, a naturally occurring virus (e.g., a naturally occurring APMV) is not genetically engineered or otherwise altered by the hand of man. 
     As used herein, the terms “subject” or “patient” are used interchangeably. As used herein, the terms “subject” and “subjects” refers to an animal. In some embodiments, the subject is a mammal including a non-primate (e.g., a camel, donkey, zebra, bovine, horse, horse, cat, dog, rat, and mouse) and a primate (e.g., a monkey, chimpanzee, and a human). In some embodiments, the subject is a non-human mammal. In certain embodiments, the subject is a pet (e.g., dog or cat) or farm animal (e.g., a horse, pig or cow). In specific embodiments, the subject is a human. In certain embodiments, the mammal (e.g., human) is 4 to 6 months old, 6 to 12 months old, 1 to 5 years old, 5 to 10 years old, 10 to 15 years old, 15 to 20 years old, 20 to 25 years old, 25 to 30 years old, 30 to 35 years old, 35 to 40 years old, 40 to 45 years old, 45 to 50 years old, 50 to 55 years old, 55 to 60 years old, 60 to 65 years old, 65 to 70 years old, 70 to 75 years old, 75 to 80 years old, 80 to 85 years old, 85 to 90 years old, 90 to 95 years old or 95 to 100 years old. In specific embodiments, the subject is an animal that is not avian. 
     As used herein, the terms “therapies” and “therapy” can refer to any protocol(s), method(s), agent(s) or a combination thereof that can be used in the treatment cancer. In certain embodiments, the term “therapy” refers to an oncolytic virus described herein (e.g., an APMV). In other embodiments, the term “therapy” refers to an agent that is not an oncolytic virus described herein (e.g., an APMV). 
    
    
     
       4. BRIEF DESCRIPTION OF THE FIGURES 
         FIG.  1   . Rescue of rNDV from a cloned cDNA. BSR-T7 cells growing in a 6 well plate are infected with virus MVA-T7, to express the T7 RNA polymerase. After 1 h., cells are transfected with plasmid pNDV-LaSota-L289A, and helper plasmids pTM1.NP, pTM1.P and pTM1.L. Next day cells and supernatants are inoculated into 10 day-old embryonated chicken eggs to amplify the rescued virus. After 3 days the allantoic fluid is harvested and analyzed for the presence of virus by hemagglutination (HA) assay. HA positive samples are further characterized to confirm the presence and expression of the inserted gene. 
         FIG.  2   . Schematic of the protocol used for the construction of the rescue plasmid pNDV-LaSota-L289A-mVEGF-C. (Not to scale). The open reading frame encoding the murine VEGF-C (mVEGF-C) protein is amplified by PCR using primers that incorporate additional sequences: Forward primer: Sac II restriction site+NDV regulatory sequences (gene end+intergene+gene start)+Kozac sequences for optimal translation. Reverse primer: additional nucleotides (rule of 6)+Sac II restriction site. Next, the amplified PCR product is cloned into the Sac II site of plasmid pNDV-LaSota-L289A to generate the rescue plasmid pNDV-LaSota-L289A-mVEGF-C. Primer sequences are provided in Table 1. 
         FIG.  3   . Schematic of the protocol used for the cloning of a full-length cDNA of the APMV4 genome with engineered unique restriction sites. Using purified viral RNA as template, each viral gene was amplified by RT-PCR with primers that introduced unique restriction sites as indicated. Next, PCR products 1.1, 1.2 and 1.3 (viral genes NP, P and M, respectively) were cloned in the multicloning site of plasmid pUC-18 to generate plasmid pUC-APMV4-1. PCR products 2.1 and 2.2 (genes F and HN, respectively) were cloned into pUC-APMV4-2 and PCR products 3.1 and 3.2 (gene L) were cloned into pUC-APMV4-3. Next, plasmids 1 and 2 were combined to create pUC-APMV4-1+2 and finally plasmids 1+2 and 3 were combined to generate pUC-APMV4-1+2+3 that contains a full-length copy of the APMV4 genome with engineered unique restriction sites between each viral gene. Primer sequences are provided in Table 1. 
         FIG.  4   . Schematic of the protocol used for the cloning of the helper plasmids expressing APMV4 proteins NP, P and L. (Not to scale) Using as template plasmids pUC-APMV4-1 and pUC-APMV4-3, the open reading frames coding the viral proteins NP, P and L were amplified by PCR. Next, the amplified PCR products were cloned into the pTM1 vector using the Nco I and Pst I restriction sites. Primer sequences are provided in Table 1. 
         FIG.  5   . Schematic of the protocol used for the rescue of rAPMV4 from a cloned cDNA. BSR-T7 cells growing in a 6 well plate are infected with virus MVA-T7, to express the T7 RNA polymerase. After 1 h., cells are transfected with plasmid pRz-APMV4, and helper plasmids pTM1-APMV4.NP, pTM1-APMV4.P and pTM1-APMV4.L. Next day cells and supernatants are inoculated into 10 day-old embryonated chicken eggs to amplify the rescued virus. After 3 days the allantoic fluid is harvested and analyzed for the presence of virus by hemagglutination (HA) assay. HA positive samples are further characterized to confirm the presence and expression of the inserted gene. 
         FIG.  6   . Schematic of the protocol used for the construction of the rescue plasmid pRz-APMV4-mVEGF-C. (Not to scale). The rescue plasmid containing a codon optimized mVEGF-C gene is constructed in 2 steps. First, a synthetic DNA encoding a codon optimized mVEGF-C protein is amplified by PCR and cloned at the unique Sal I site of plasmid pUC-APMV4-1. Next, a Nhe I-Sbf I is replaced in the plasmid pRz-APMV4 to generate the rescue plasmid pRz-APMV4-mVEGF-C. Primer sequences are provided in Table 1. 
         FIGS.  7 A- 7 E . Oncolytic activity of APMVs (namely, NDV LS289A or APMV-4) in B16-F10 and B16-VEGF-C+ syngeneic murine melanoma tumor model.  FIG.  7 A  shows a schematic of the experimental set up for Study 1.  FIG.  7 B  shows an analysis of tumor growth rate. Points represent average of tumor volume per experimental group at the indicated time point. Error bars correspond to standard deviation of each group.  FIG.  7 C  shows individual tumor growth curves. Each point represents tumor volume per mice at the indicated time point.  FIG.  7 D  shows overall survival.  FIG.  7 E  shows a comparative analysis between experimental groups, of treated B16-F10 or B16-VEGF-C+ tumor-bearing mice. 
         FIGS.  8 A- 8 C . Re-challenge.  FIG.  8 A : Right panel: schematic of the re-challenge experimental set up for the Study 1. Left panel: analysis of tumor growth rate. Points represent average of tumor volume per experimental group at the indicated time point. Error bars correspond to standard deviation of each group.  FIG.  8 B : individual tumor growth curves. Each point represents tumor volume per mice at the indicated time point.  FIG.  8 C : post-re-challenge overall survival analysis of Study 1. 
         FIGS.  9 A- 9 D . Oncolytic activity of APMVs (namely, NDV LS289A or APMV-4) in B16-F10 and B16-VEGF-C+ syngeneic murine melanoma tumor models.  FIG.  9 A  shows a schematic of the experimental set up for Study 2.  FIG.  9 B  shows an analysis of tumor growth rate. Points represent average of tumor volume per experimental group at the indicated time point. Error bars correspond to standard deviation of each group.  FIG.  9 C  shows individual tumor growth curves. Each point represents tumor volume per mice at the indicated time point.  FIG.  9 D  shows overall survival analysis pre-re-challenge. 
         FIGS.  10 A- 10 D . Re-challenge.  FIG.  10 A  shows a schematic of the re-challenge experimental set up for Study 2.  FIG.  10 B  shows analysis of tumor growth rate. Points represent average of tumor volume per experimental group at the indicated time point. Error bars correspond to standard deviation of each group.  FIG.  10 C  shows survival post-re-challenge.  FIG.  10 D  shows survival analysis summary for Study 2. 
         FIGS.  11 A- 11 C : VEGF-C potentiates anti-tumor immune response stimulated by the viral dsRNA mimic poly(I:C).  FIG.  11 A  shows a schematic of the experimental set up.  FIG.  11 B  shows analysis of tumor growth rate. Points represent average of tumor volume per experimental group, error bars indicate standard deviation.  FIG.  11 C  shows individual tumor growth curves. 
         FIG.  12   . Schematic representation of the viral constructs overexpressing full-length or mature VEGF-C. PT7, T7 promoter NP, nucleoprotein; P, phosphoprotein; M, matrix protein, F, fusion protein; HN, hemagglutinin-neuraminidase; L, large polymerase protein. HDR, hepatitis delta ribozyme. TT7, T7 terminator sequence. 
         FIGS.  13 A- 13 C . Characterization of VEGF-C expression in cells transduced with NDV/VEGF-C wt constructs.  FIG.  13 A : Immunofluorescent staining of Vero cells infected with NDV/VEGF-C FL-WT using an anti-VEGF-C antibody.  FIG.  13 B : ELISA of conditioned media from 293T cells transduced with the NDV/VEGF-C constructs as indicated (full length and mature forms, WT and mutants thereof). Conditioned media was collected after 24 hours.  FIG.  13 C : Western blot of supernatants from 293T cells transduced with NDV/VEGF-C constructs as indicated. Scale bars: 50 μm. 
         FIGS.  14 A- 14 F . Effects of NDV/VEGF-C FL-WT and dNdC-WT on B16F10 tumors.  FIG.  14 A : Schematic representation of the NDV viral treatment schedule.  FIG.  14 B : Effects of treatment of tumors with NDV/VEGF-C FL-WT construct in comparison to NDV on survival of mice bearing B16F10 tumors.  FIG.  14 C : Tumor growth curves with different treatments as indicated. Each line represents tumor from one mouse.  FIG.  14 D : Tumor growth curves showing average values for each treatment type.  FIG.  14 E : Survival data for each of the treatments as indicated.  FIG.  14 F : Immunohistochemical staining (IHC) of tumors treated with NDV or NDV/VEGF-C FL-WT for VEGF-C, LYVE-1 and CD8, as indicated. 
         FIGS.  15 A- 15 F . Effects of NDV treatment and VEGF-C on tumor growth and long-term survival of mice with B16F10 tumors.  FIG.  15 A : Experimental design showing tumor treatment schedule.  FIG.  15 B  Tumor growth of B16F10 cells transfected with control vector not expressing VEGF-C, and treated with NDV.  FIG.  15 C : Tumor growth of B16F10 cells constitutively expressing VEGF-C and treated with NDV.  FIG.  15 D : Mouse post-treatment of B16F10/VEGF-C tumor with NDV. Note white patches of hair at the sites where tumors regressed.  FIG.  15 E : Survival of mice following treatments as indicated.  FIG.  15 F : Tumor growth at initial injection and following re-challenge of survivor mice, as indicated. 
         FIGS.  16 A- 16 F . Immunophenotyping of B16F10 tumors by Aurora spectral flow cytometry.  FIG.  16 A : Distribution of T-cell and NK cell phenotypes in B16F10/VEGF-C tumors treated with NDV, compared to B16F10 mock control.  FIG.  16 B : Distribution of T-cell and NK cell phenotypes in B16F10/VEGF-C tumors treated with NDV, compared to B16F10 treated with NDV.  FIG.  16 C : Distribution of immune cell phenotypes in B16F10 and B16F10/VEGF-C tumors treated as indicated. Flow cytometry data for T-cell and NK cell activation markers.  FIG.  16 D : Fraction of activated vs. all CD45+ immune cells in tumors treated as indicated.  FIG.  16 E : Fraction of activated cells across different treatment groups.  FIG.  16 F : Fraction of main activated immune cell subtypes in VEGF-C/NDV group. Question marks indicate that the exact immune cell subset could not be determined based on the marker combination. 
         FIG.  17 A- 17 M . Effects of NDV treatment and VEGF-C on the distribution of immune cells in tumors. Effects of NDV treatment and VEGF-C on the distribution of immune cells in tumors.  FIGS.  17 A- 17 C : Immunofluorescent staining of B16F10 PBS-treated tumors for CD8 ( FIG.  17 A ), CD4 ( FIG.  17 B ), and CD11c ( FIG.  17 C ).  FIGS.  17 D- 17 F : Immunofluorescent staining of B16F10/VEGF-C NDV-treated tumors for CD8 ( FIG.  17 D ), CD4 ( FIG.  17 E ), and CD11c ( FIG.  17 F ).  FIGS.  17    G and  17 H: Immunofluorescent staining for lymphatics (LYVE-1) in tumors as indicated and ( FIG.  17 I ) for CD8+ T-cells in the same section shown in ( FIG.  17 H ). Note high CD8+ T-cell densities in tumor areas with high lymphatic vessel densities. ( FIG.  17 J ) Quantification of CD8+ T-cells in tumors based on immunostaining. (K) Conventional flow cytometry analysis of immune cells in tumors. CD8+CD25+ effector memory T-cells are shown.  FIGS.  17 L and  17 M : Quantification of lymphatic ( FIG.  17 L ) and blood ( FIG.  17 M ) vessel densities in tumors as indicated. EV/PBS, B16F10 cells transfected with empty vector control and tumors treated with PBS. VEGF-C/NDV, B16F10 cells transfected with VEGF-C and tumors treated with NDV. 
         FIGS.  18 A- 18 B . Immunophenotyping of lymph nodes draining B16F10 tumors by Aurora spectral flow cytometry.  FIG.  18 A : Distribution of immune cell phenotypes in sentinel lymph nodes of B16F10 and B16F10/VEGF-C tumors treated as indicated.  FIG.  18 B : Distribution of immune cell phenotypes in contralateral lymph nodes of B16F10 and B16F10/VEGF-C tumors treated as indicated. Question marks indicate that the exact immune cell subset could not be determined based on the marker combination. 
     
    
    
     5. DETAILED DESCRIPTION 
     5.1 Oncolytic Viruses 
     In one aspect, provided herein are viruses that may be used in a method for treating cancer described herein. In some embodiments, the virus can be any virus known in the art, including, e.g., an adeno-associated virus (“AAV”; e.g., AAV1-AAV9). In other embodiments, the virus is not an adeno-associate virus (e.g., is not AAV1-AAV9). In a specific aspect, provided herein are oncolytic viruses that may be used in a method for treating cancer described herein. In a specific embodiment, an oncolytic virus is a virus that when injected into a tumor results in tumor regression. In another specific embodiment, an oncolytic virus is a virus that selectively replicates in and kills cancer cells, and spreads within the tumor. In another specific embodiment, an oncolytic virus is a virus that selectively replicates in and kills cancer cells, and spreads within the tumor without causing any significant damage to normal tissue. In some embodiments, an in vitro or ex vivo assay known to one skilled in the art is used to determine the selectively of a virus to replicate in cancer cells versus non-cancerous cells (e.g., healthy cells). In one embodiment, a virus selectively replicates in cancer cells if a statistically significant increase in the number of virus particles is detected in cancer cells in an in vitro assay or ex vivo assay relative to the number of virus particles detected in non-cancerous cells (e.g., healthy cells) in the same assay after incubation with the virus. In another embodiment, a virus selectively kills cancer cells if a statistically significant amount of the cancer cells are killed in an in vitro or ex vivo assay relative to the amount of non-cancerous cells (e.g., healthy cells) killed in the same assay. In one embodiment, an oncolytic virus naturally preferentially replicates in cancer cells and is non-pathogenic in humans. An oncolytic virus may be non-pathogenic in humans due to elevated sensitivity to innate antiviral signal or dependence on oncogenic signaling pathways. In some embodiments, an oncolytic virus is a parovirus (e.g., an autonomous parvovirus), a myxoma virus, an avian paramyxovirus (e.g., Newcastle disease virus), a reovirus, or Seneca valley virus. In one embodiment, an oncolytic virus is wild-type parvovirus H1 (ParvOryx). In another embodiment, an oncolytic virus is Vesicular stomatitis virus. In another embodiment, an oncolytic virus is an avian paramyxovirus. See Section 5.1.1, infra, regarding avian paramyxoviruses. 
     In certain embodiments, an oncolytic virus is a virus that is genetically engineered with mutations (e.g., deletions and/or substitutions) in genes required for replication in normal, but not cancer cells. In some embodiments, an oncolytic virus is a genetically engineered influenza virus, measles virus, poliovirus, vaccinia virus, poxvirus, picornavirus, alphavirus, retrovirus, rhabdovirus, reovirus, adenovirus, herpes simplex virus, or vesicular stomatitis virus. In a specific embodiment, such viruses are attenuated. In one embodiment, an oncolytic virus is an E1A/E1B-deleted adenovirus (ONYX015) (see, e.g., Cohen and Rudin, 2001, Curr. Opin. Investig. Drugs 2(12): 1770-1775, which is incorporated by reference in its entirety, for information regarding ONYX015. In another embodiment, an oncolytic virus is the adenovirus is H101, a conditionally replicative adenovirus, was generated by both E1B and E3 gene deletion (see, e.g., Kasuya et al., 2007, Curr Cancer Drug Targets. 7:123-125, which is incorporated by reference in its entirety, for information regarding H101). In another embodiment, an oncolytic virus is adenovirus known as Delta-24-RGD (DNX-2401). In another embodiment, an oncolytic virus is an attenuated influenza virus, (e.g., an influenza virus comprising a truncated NS1 protein such as described in U.S. Pat. Nos. 10,098,945; 8,057,803; 8,124,101; 8,137,676; 6,866,853; 6,669,943; 6,468,544; 8,137,676; and 9,387,240, each of which is incorporated herein by reference in its entirety). In another embodiment, an oncolytic virus is HSV1716 (Seprehvir®). In another embodiment, an oncolytic virus is G207. In another embodiment, an oncolytic virus is Pelareorep (Reolysin®). In certain embodiments, an oncolytic virus for use in a method for treating cancer described herein may be engineered to express a heterologous protein. For example, an oncolytic virus may be engineered to express a checkpoint inhibitor (e.g., an antibody that specifically binds to PD-1 and blocks binding of PD-1 to PDL1, PDL2 or both, such as pembrolizumab or nivolumab; an antibody that specifically binds to PDL1 and blocks binding of PDL1 to PD1, CD80 or both, such as atezolizumab, durvalumab, or cemiplimab; an antibody that specifically binds to CLTA-4 and block the interaction of CTLA-4 with its ligands B7.1 and B7.2, such as ipilimumab or tremelimumab; and an antibody that specifically binds to TIM-3); a cytokine (e.g., IL-2, IL-12, IL-15, IFN alpha/beta, 41-BB, CD40L, Flt3L, CCL3, CCL5, GM-CSF, etc.); an agonist of a co-stimulatory receptor (e.g., an agonist of ICOS, ICOS-L, OX40, OX40L, etc.); or a cancer antigen (e.g., a tumor associated antigen). See, e.g., Section 5.7.2 for examples of checkpoint inhibitors and agonists of co-stimulatory receptors. In some embodiments, an oncolytic virus for use in a method for treating cancer described herein is pexastimogene devacirepvec (Pexa-Vec, formerly named JX-594), ONCOS (adeno Δ24-RGD-GM-CSF insertion), herpes virus OrienX010, ICOVIR-5, Talimogene Laherparepvec (T-VEC, Imlygic®), VV JX-594, Ad Ad5/3-D24-GMCSF, or CG0070. In other embodiments, an oncolytic virus is not engineered to express a checkpoint inhibitor, a cytokine, an agonist of a co-stimulatory receptor, or a cancer antigen. 
     In certain embodiments, an oncolytic virus for use in a method for treating cancer described herein is not engineered to express a heterologous protein. In some embodiments, an oncolytic virus for use in a method for treating cancer is not engineered to express a cancer antigen (e.g., a tumor associated antigen). In certain embodiments, an oncolytic virus for use in a method for treating cancer is not engineered to express a heterologous viral antigen. In some embodiments, an oncolytic virus for use in a method for treating cancer is not engineered to express a bacterial antigen, a fungal antigen, a protozoal antigen, or a helminth antigen. 
     5.1.1 Avian Paramyxoviruses 
     Any APMV-1 (otherwise known as Newcastle disease virus or NDV), APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain, including, but not limited to, naturally-occurring strains, variants or mutants, mutagenized viruses, genetically engineered viruses, or a combination thereof may be used in the methods for treating cancer described herein. See Table 2 for exemplary APMV sequences. One skilled in the art would understand that viruses may undergo mutation when cultured, passaged or propagated. The APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain may contain these naturally occurring mutations, in addition to mutations introduced for cloning purposes. The APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain may be a homogenous or heterogeneous population with none, or one or more of these mutations. In certain embodiments, the APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain that is used in a method of treating cancer described herein is a lytic strain. In other embodiments, the APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain that is used in a method of treating cancer described herein is a non-lytic strain. In a specific embodiment, the APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain that is used in a method of treating cancer described herein is naturally occurring. In a specific embodiment, the APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain that is used in a method of treating cancer described herein is avirulent in an avian(s) by a method(s) described herein or known to one of skill in the art. In a specific embodiment, the APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain that is used in a method of treating cancer described herein is recombinantly produced. In certain embodiments, the APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain that is used in a method of treating cancer described herein is genetically engineered to be attenuated in a manner that attenuates the pathogenicity of the virus in birds. 
     In another specific embodiment, the APMV-1, APMV-2, APMV-3, APMV-4, APMV-6, APMV-7, APMV-8, or APMV-9 strain that is used in a method of treating cancer described herein has an intracerebral pathogenicity index in day-old chicks of the  Gallus gallus  species of less than 0.7. In certain specific embodiments, the APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain that is used in a method of treating cancer described herein is not pathogenic as assessed by intracranial injection of 1-day-old chicks with the virus, and disease development and death as scored for 8 days. In some embodiments, the APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain that is used in a method of treating cancer described herein has an intracranial pathogenicity index of less than 0.7, less than 0.6, less than 0.5, less than 0.4, less than 0.3, less than 0.2 or less than 0.1. In some embodiments, the APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain that is used in a method of treating cancer described herein has an intracranial pathogenicity index between 0.7 to 0.1, 0.6 to 0.1, 0.5 to 0.1 or 0.4 to 0.1. In certain embodiments, the APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain that is used in a method of treating cancer described herein has an intracranial pathogenicity index of zero. See, e.g., one or more of the following references for a description of an assay that may be used to assess the pathogenicity of an APMV in birds: Hines, N. L. and C. L. Miller, Avian paramyxovirus serotype-1: a review of disease distribution, clinical symptoms, and laboratory diagnostics. Vet Med Int, 2012. 2012: p. 708216; Kim S-H, Xiao S, Shive H, Collins P L, Samal S K., 2012: Replication, Neurotropism, and Pathogenicity of Avian Paramyxovirus Serotypes 1-9 in Chickens and Ducks. PLoS ONE. 7(4): e34927; Subbiah, M., Xiao, S., Khattar, S. K., Dias, F. M., Collins, P. L., &amp; Samal, S. K., 2010: Pathogenesis of two strains of Avian Paramyxovirus serotype 2, Yucaipa and Bangor, in chickens and turkeys. Avian Diseases, 54(3), 1050-1057; Kumar S, Militino Dias F, Nayak B, Collins P L, Samal S. K., 2010: Experimental avian paramyxovirus serotype-3 infection in chickens and turkeys. Veterinary Research.; 41(5):72; Ryota Tsunekuni, Hirokazu Hikono, Takehiko Saito., 2014: Evaluation of avian paramyxovirus serotypes 2 to 10 as vaccine vectors in chickens previously immunized against Newcastle disease virus. Veterinary Immunology and Immunopathology; 160(3-4):184-191; and www.oie.int/fileadmin/Home/fr/Health_standards/tahm/2.03.14 NEWCASTLE DIS.pdf, each of which is incorporated herein by reference in its entirety. In a specific embodiment, the APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain is a recombinant APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain, respectively. 
     In another specific embodiment, the APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain that is used in a method of treating cancer described herein is naturally occurring and has an intracerebral pathogenicity index in day-old chicks of the  Gallus gallus  species of less than 0.7. In a specific embodiment, the APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain that is used in a method of treating cancer described herein is a recombinant APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain, respectively, and has an intracerebral pathogenicity index in day-old chicks of the  Gallus gallus  species of less than 0.7. 
     In a specific embodiment, an APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 that is used in a method of treating cancer described herein decreases tumor growth and increases survival in a B16-F10-VEGF-C+ syngeneic murine melanoma model as compared to tumor growth and survival in B16-F10-VEGF-C+ syngeneic murine melanoma model administered phosphate buffered saline (PBS) as assessed by a method known in the art or described herein (e.g., in Section 6, infra). 
     In a specific embodiment, an APMV strain is used in a method for treating cancer described herein is an AMPV-1 or APMV-4 described in Section 6, infra. 
     In one embodiment, an APMV-2 strain is used in a method for treating cancer described herein, wherein the APMV-2 strain is APMV-2 Chicken/California/Yucaipa/1956. See, e.g., GenBank No. EU338414.1 for the complete genomic cDNA sequence of APMV-2 Chicken/California/Yucaipa/1956. In another embodiment, an APMV-3 strain is used in a method for treating cancer described herein, wherein the APMV-3 strain is APMV-3 turkey/Wisconsin/68. See, e.g., GenBank No. EU782025.1 for the complete genomic cDNA sequence of APMV-3 turkey/Wisconsin/68. In another embodiment, an APMV-6 strain is used in a method for treating cancer described herein, wherein the APMV-6 strain is APMV-6/duck/Hong Kong/18/199/77. See, e.g., GenBank No. EU622637.2 for the complete genomic cDNA sequence of APMV-6/duck/Hong Kong/18/199/77. In another embodiment, an APMV-7 strain is used in a method for treating cancer described herein, wherein the APMV-7 strain is APMV-7/dove/Tennessee/4/75. See, e.g., GenBank No. FJ231524.1 for the complete genomic cDNA of APMV-7/dove/Tennessee/4/75. In another embodiment, an APMV-8 strain is used in a method for treating cancer described herein, wherein the APMV-8 strain is APMV-8/Goose/Delaware/1053/76. See, e.g., GenBank No. FJ619036.1 for the complete genomic cDNA sequence of APMV-8/Goose/Delaware/1053/76. In another embodiment, an APMV-9 is used in a method for treating cancer described herein, wherein the APMV-9 strain is APMV-9 duck/New York/22/1978. See, e.g., GenBank No. NC 025390.1 for the complete genomic cDNA sequence of APMV-9 duck/New York/22/1978. 
     In a specific embodiment, an APMV-1 is used in a method for treating cancer described herein. In a specific embodiment, the APMV-1 used in a method for treating cancer described herein is a naturally-occurring strain. In certain embodiments, the APMV-1 is a lytic strain. In other embodiments, the APMV-APMV-1 used in a method for treating cancer described herein is a non-lytic strain. In certain embodiments, the APMV-1 used in a method for treating cancer described herein is lentogenic strain. In some embodiments, the APMV-1 used in a method for treating cancer described herein is a mesogenic strain. In other embodiments, the APMV-1 used in a method for treating cancer described herein is a velogenic strain. See, e.g., Newcastle Disease, Avian Paramyoxvirus-1 Infection, Goose Paramyoxvirus Infection, Ranikhet disease, the Center for Food Security &amp; Public Health, Iowa State University, Institute for International Cooperation in Animal Biologies, College of Veterinary Medicine, Iowa State University, pp. 1-9 (January 2016) for a discussion regarding lentogenic, mesogenic and velogenic APMV-1 (otherwise referred to as NDV) strains, which is incorporated herein by reference in its entirety. Specific examples of APMV-1 strains include, but are not limited to, the 73-T strain, NDV HUJ strain, Ulster strain (see, e.g., GenBank No. U25837), MTH-68 strain, Italien strain (see, e.g., GenBank No. EU293914), Hickman strain (see, e.g., Genbank No. AF309418), PV701 strain, Hitchner B1 strain (see, e.g., GenBank No. AF309418 or NC 002617), La Sota strain (see, e.g., GenBank Nos. AY845400 and JF950510.1 and GI No. 56799463), YG97 strain (see, e.g., GenBank Nos. AY351959 or AY390310), MET95 strain (see, e.g., GenBank No. AY143159), Roakin strain (see, e.g., GenBank No. AF124443), and F48E9 strain (see, e.g., GenBank Nos. AF163440 and U25837). In a specific embodiment, the APMV-1 used in a method for treating cancer described herein that is the Hitchner B 1 strain. In another specific embodiment, the APMV-1 used in a method for treating cancer described herein is a B 1 strain as identified by GenBank No. AF309418 or NC_002617. In another specific embodiment, the APMV-1 used in a method for treating cancer described herein is the NDV identified by ATCC No. VR2239. In another specific embodiment, the APMV-1 used in a method for treating cancer described herein is an NDV described in U.S. Pat. No. 10,035,984, which is incorporated herein by reference in its entirety. 
     In a specific embodiments, an APMV-1 that is used in a method of treating cancer described herein is genetically modified. In one embodiment, a genome of an APMV-1 used in a method of treating cancer described herein is engineered to express a mutated F protein with a mutated cleavage site. In a specific embodiment, the APMV-1 used in a method of treating cancer described herein is engineered to express a mutated F protein in which the cleavage site of the F protein is mutated to produce a polybasic amino acid sequence, which allows the protein to be cleaved by intracellular proteases, which makes the virus more effective in entering cells and forming syncytia. In another specific embodiment, the APMV-1 used in a method of treating cancer described herein is engineered to express a mutated F protein in which the cleavage site of the F protein is replaced with a mutated cleavage site containing one or two extra arginine residues, allowing the mutant cleavage site to be activated by ubiquitously expressed proteases of the furin family. Specific examples of NDVs that express such a mutated F protein include, but are not limited to, rNDV/F2aa and rNDV/F3aa. For a description of mutations introduced into a NDV F protein to produce a mutated F protein with a mutated cleavage site, see, e.g., Park et al. (2006) Engineered viral vaccine constructs with dual specificity: avian influenza and Newcastle disease. PNAS USA 103: 8203-2808, which is incorporated herein by reference in its entirety. 
     In a specific embodiment, an APMV-1 strain is used in a method for treating cancer described herein. In another embodiment, an APMV-1 strain that is naturally occurring is used in a method of treating cancer described herein. In a specific embodiment, an APMV-1 strain that is naturally occurring and has an intracerebral pathogenicity index in day-old chicks of the  Gallus gallus  species of less than 0.7 is used in a method of treating cancer described herein. In a specific embodiment, an APMV-1 that is used in a method of treating cancer described herein is an APMV-1 with a genome that has 80%, 85%, 90%, 95% or higher percent identity to the genome of a LaSota strain (e.g., SEQ ID NO: 83 or 84). 
     In a specific embodiment, an APMV-1 used in a method of treating cancer described herein is engineered to express a mutated F protein with the amino acid mutation L289A (i.e., an L to A mutation at the amino acid position corresponding to L289 of the LaSota F protein). For a description of the L289A mutation, see, e.g., Sergei et al. (2000) A Single Amino Acid Change in the Newcastle Disease Virus Fusion Protein Alters the Requirement for UN Protein in Fusion. Journal of Virology 74(11): 5101-5107, which is incorporated herein by reference in its entirety. In specific embodiments, the L289A mutated F protein possesses one, two or three arginine residues in the cleavage site. In a specific embodiment, the APMV-1 used in a method of treating cancer described herein is the LaSota strain, which has been engineered to express a mutated F protein with the amino acid mutation L289A (i.e., an L to A mutation at the amino acid position corresponding to L289 of the LaSota F protein). In a specific embodiment, the genetically modified NDV LaSota strain comprises a packaged genome, wherein the packaged genome comprises the negative sense RNA transcribed from the cDNA sequence set forth in SEQ ID NO: 83 or 84. 
     In some embodiments, an APMV-1 used in a method of treating cancer described herein is the NDV disclosed in Kim et al., 2017, PLOS ONE 12(3): e0173965 and Kim et al., 2016, J. of General Virology 97: 1297-1303, each of which is incorporated herein by reference in its entirety. 
     In certain embodiments, an APMV-1 used in a method of treating cancer described herein comprises a mutated F protein with an F protein cleavage site of NDV LaSota strain or glycoprotein B of cytomegalovirus (CMV). In a specific embodiment, an APMV-1 used in a method of treating cancer described herein comprises a mutated F protein with an F protein cleavage having one of the following sequence modifications: S116:  111 H-N-R-T-K-S/F 117  (SEQ ID NO: 91); S116K:  111 H-N-K-T-K-S/F 117  (SEQ ID NO: 92); S116M:  111 H-N-R-M-K-S/F 117  (SEQ ID NO: 93); S116KM:  111 H-N-K-M-K-S/F-I 118  (SEQ ID NO: 94); or R116:  111 H-N-R-T-K-R/F-I 118  (SEQ ID NO: 95), such as described in International Patent Application No. WO 2015/032755. See, e.g., International Patent Application Publication No. WO 2015/032755 for a description of the types of mutated F protein cleavage sites that may be engineered into an NDV F protein, which is incorporated herein by reference in its entirety. In some embodiments, the mutated F protein is in addition to the backbone NDV F protein. In specific embodiments, the mutated F protein replaces the backbone NDV F protein. 
     In a specific embodiment, an APMV-4 strain is used in a method for treating cancer described herein. In another embodiment, an APMV-4 strain that is naturally occurring is used in a method of treating cancer described herein. In a preferred embodiment, an APMV-4 strain that is naturally occurring and has an intracerebral pathogenicity index in day-old chicks of the  Gallus gallus  species of less than 0.7 is used in a method of treating cancer described herein. In a preferred embodiment, the APMV-4 that is used in a method of treating cancer described herein is APMV-4/Duck/Hong Kong/D3/1975 strain. See, e.g., GenBank No. FJ177514.1 or SEQ ID NO: 78 for the complete genomic cDNA sequence of APMV-4/duck/Hong Kong/D3/75. In a specific embodiment, an APMV-4 that is used in a method of treating cancer described herein is APMV-4/Duck/China/G302/2012 strain, APMV4/mallard/Belgium/15129/07 strain, APMV4/Uriah_aalge/Russia/Tyuleniy_Island/115/2015 strain, APMV-4/Egyptian goose/South Africa/N1468/2010 strain, or APMV4/duck/Delaware/549227/2010 strain. In a specific embodiment, an APMV-4 that is used in a method of treating cancer described herein is an APMV-4 with a genome that has 80%, 85%, 90%, 95% or higher percent identity to the genome of APMV-4/Duck/Hong Kong/D3/1975 strain. In one embodiment, an APMV-4 that is used in a method of treating cancer described herein is APMV-4/Duck/China/G302/2012 strain. See, e.g., GenBank No. KC439346.1 or SEQ ID NO: 81 for the complete genomic cDNA sequence of APMV-4/Duck/China/G302/2012 strain. In a specific embodiment, an APMV-4 that is used in a method of treating cancer described herein is an APMV-4 with a genome that has 80%, 85%, 90%, 95% or higher percent identity to the genome of APMV-4/Duck/China/G302/2012 strain. In another embodiment, an APMV-4 that is used in a method of treating cancer described herein is APMV-4/Uriah_aalge/Russia/Tyuleniy_Island/115/2015 strain. See, e.g., GenBank No. KU601399.1 or SEQ ID NO: 79 for the complete genomic cDNA sequence of APMV-4/Uriah_aalge/Russia/Tyuleniy_Island/115/2015 strain. In a specific embodiment, an APMV-4 that is used in a method of treating cancer described herein is an APMV-4 with a genome that has 80%, 85%, 90%, 95% or higher percent identity to the genome of APMV-4/Uriah_aalge/Russia/Tyuleniy_Island/115/2015 strain. In another embodiment, the APMV-4 that is used in a method of treating cancer described herein is APMV4/duck/Delaware/549227/2010 strain. See, e.g., GenBank No. JX987283.1 or SEQ ID NO: 82 for the complete genomic cDNA sequence of APMV4/duck/Delaware/549227/2010 strain. In a specific embodiment, an APMV-4 that is used in a method of treating cancer described herein is an APMV-4 with a genome that has 80%, 85%, 90%, 95% or higher percent identity to the genome of APMV4/duck/Delaware/549227/2010 strain. In another embodiment, an APMV-4 that is used in a method of treating cancer described herein is APMV4/mallard/Belgium/15129/07 strain. See, e.g., GenBank No. JN571485 or SEQ ID NO: 77 for the complete genomic cDNA sequence of APMV4/mallard/Belgium/15129/07 strain. In a specific embodiment, an APMV-4 that is used in a method of treating cancer described herein is an APMV-4 with a genome that has 80%, 85%, 90%, 95% or higher percent identity to the genome of APMV4/mallard/Belgium/15129/07 strain. In another embodiment, the APMV-4 that is used in a method of treating cancer described herein is APMV-4/Egyptian goose/South Africa/N1468/2010 strain. See, e.g., GenBank No. JX133079.1 or SEQ ID NO: 80 for the complete genomic cDNA sequence of APMV-4/Egyptian goose/South Africa/N1468/2010 strain. In a specific embodiment, an APMV-4 that is used in a method of treating cancer described herein is an APMV-4 with a genome that has 80%, 85%, 90%, 95% or higher percent identity to the genome of APMV-4/Egyptian goose/South Africa/N1468/2010 strain. 
     In a specific embodiment, an APMV-8 strain is used in a method for treating cancer described herein. In another embodiment, an APMV-8 strain that is naturally occurring is used in a method of treating cancer described herein. In a specific embodiment, an APMV-8 strain that is naturally occurring and has an intracerebral pathogenicity index in day-old chicks of the  Gallus gallus  species of less than 0.7 is used in a method of treating cancer described herein. In a specific embodiment, an APMV-8 that is used in a method of treating cancer described herein is APMV-8/Goose/Delaware/1053/76. See, e.g., GenBank No. FJ619036.1 for the complete genomic cDNA sequence of APMV-8/Goose/Delaware/1053/76. In a specific embodiment, an APMV-8 that is used in a method of treating cancer described herein is an APMV-8 with a genome that has 80%, 85%, 90%, 95% or higher percent identity to the genome of APMV-8/Goose/Delaware/1053/76. 
     In a specific embodiment, an APMV-7 strain is used in a method for treating cancer described herein. In another embodiment, an APMV-7 strain that is naturally occurring is used in a method of treating cancer described herein. In a preferred embodiment, an APMV-7 strain that is naturally occurring and has an intracerebral pathogenicity index in day-old chicks of the  Gallus gallus  species of less than 0.7 is used in a method of treating cancer described herein. In a specific embodiment, an APMV-7 that is used in a method of treating cancer described herein is APMV-7/dove/Tennessee/4/75. See, e.g., GenBank No. FJ231524.1 for the complete genomic cDNA of APMV-7/dove/Tennessee/4/75. In a specific embodiment, an APMV-7 that is used in a method of treating cancer described herein is and APMV-7 with a genome that has 80%, 85%, 90%, 95% or higher percent identity to the genome of APMV-7/dove/Tennessee/4/75. 
     In a specific embodiment, an APMV-2 strain is used in a method for treating cancer described herein. In another embodiment, an APMV-2 strain that is naturally occurring is used in a method of treating cancer described herein. In a preferred embodiment, an APMV-2 strain that is naturally occurring and has an intracerebral pathogenicity index in day-old chicks of the  Gallus gallus  species of less than 0.7 is used in a method of treating cancer described herein. In a specific embodiment, an APMV-2 that is used in a method of treating cancer described herein is APMV-2 Chicken/California/Yucaipa/1956. See, e.g., GenBank No. EU338414.1 for the complete genomic cDNA sequence of APMV-2 Chicken/California/Yucaipa/1956. In a specific embodiment, an APMV-2 that is used in a method of treating cancer described herein is and APMV-2 with a genome that has 80%, 85%, 90%, 95% or higher percent identity to the genome of APMV-2 Chicken/California/Yucaipa/1956. 
     In a specific embodiment, an APMV-3 strain is used in a method for treating cancer described herein. In another embodiment, an APMV-3 strain that is naturally occurring is used in a method of treating cancer described herein. In a preferred embodiment, an APMV-3 strain that is naturally occurring and has an intracerebral pathogenicity index in day-old chicks of the  Gallus gallus  species of less than 0.7 is used in a method of treating cancer described herein. In a specific embodiment, the APMV-3 that is used in a method of treating cancer described herein is APMV-3 turkey/Wisconsin/68. See, e.g., GenBank No. EU782025.1 for the complete genomic cDNA sequence of APMV-3 turkey/Wisconsin/68. In a specific embodiment, an APMV-3 that is used in a method of treating cancer described herein is and APMV-3 with a genome that has 80%, 85%, 90%, 95% or higher percent identity to the genome of APMV-3 turkey/Wisconsin/68. 
     In a specific embodiment, an APMV-5 strain is used in a method for treating cancer described herein. In another embodiment, an APMV-5 strain that is naturally occurring is used in a method of treating cancer described herein. In a preferred embodiment, an APMV-5 strain that is naturally occurring and has an intracerebral pathogenicity index in day-old chicks of the  Gallus gallus  species of less than 0.7 is used in a method of treating cancer described herein. See, e.g., NCBI Reference Sequence NC 025361.1 for the complete genomic cDNA sequence of an APMV-5. 
     In a specific embodiment, an APMV-6 strain is used in a method for treating cancer described herein. In another embodiment, an APMV-6 strain that is naturally occurring is used in a method of treating cancer described herein. In a preferred embodiment, an APMV-6 strain that is naturally occurring and has an intracerebral pathogenicity index in day-old chicks of the  Gallus gallus  species of less than 0.7 is used in a method of treating cancer described herein. In a specific embodiment, an APMV-6 that is used in a method of treating cancer described herein is APMV-6/duck/Hong Kong/18/199/77. See, e.g., GenBank No. EU622637.2 for the complete genomic cDNA sequence of APMV-6/duck/Hong Kong/18/199/77. In a specific embodiment, an APMV-6 that is used in a method of treating cancer described herein is an APMV-6 with a genome that has 80%, 85%, 90%, 95% or higher percent identity to the genome of APMV-6/duck/Hong Kong/18/199/77. 
     In a specific embodiment, an APMV-9 strain is used in a method for treating cancer described herein. In another embodiment, an APMV-9 strain that is naturally occurring is used in a method of treating cancer described herein. In a preferred embodiment, an APMV-9 strain that is naturally occurring and has an intracerebral pathogenicity index in day-old chicks of the  Gallus gallus  species of less than 0.7 is used in a method of treating cancer described herein. In a specific embodiment, an APMV-9 that is used in a method of treating cancer described herein is APMV-9 duck/New York/22/1978. See, e.g., GenBank No. NC 025390.1 for the complete genomic cDNA sequence of APMV-9 duck/New York/22/1978. In a specific embodiment, an APMV-9 that is used in a method of treating cancer described herein is an APMV-9 with a genome that has 80%, 85%, 90%, 95% or higher percent identity to the genome of APMV-9 duck/New York/22/1978. 
     In certain embodiments, an APMV (e.g., AMPV-1 or APMV-4) for use in a method for treating cancer described herein may be engineered to express a heterologous protein. For example, an APMV (e.g., AMPV-1 or APMV-4) may be engineered to express a checkpoint inhibitor (e.g., an antibody that specifically binds to PD-1 and blocks binding of PD-1 to PDL1, PDL2 or both, such as pembrolizumab or nivolumab; an antibody that specifically binds to PDL1 and blocks binding of PDL1 to PD1, CD80 or both, such as atezolizumab, durvalumab, or cemiplimab; an antibody that specifically binds to CLTA-4 and block the interaction of CTLA-4 with its ligands B7.1 and B7.2, such as ipilimumab or tremelimumab; and an antibody that specifically binds to TIM3); a cytokine (e.g., IL-2, IL-12, IL-15, IFN alpha/beta, 41-BB, CD40L, Flt3L, CCL3, CCL5, GM-CSF, etc.); an agonist of a co-stimulatory receptor (e.g., an agonist of ICOS, ICOS-L, OX40, OX40L, etc.); or a cancer antigen (e.g., a tumor associated antigen). See, e.g., Section 5.7.2 for examples of checkpoint inhibitors and agonists of co-stimulatory receptors. In other embodiments, an APMV (e.g., AMPV-1 or APMV-4) for use in a method for treating cancer described herein is not engineered to express a checkpoint inhibitor, a cytokine, an agonist of a co-stimulatory receptor, or a cancer antigen. 
     In certain embodiments, an APMV (e.g., AMPV-1 or APMV-4) for use in a method for treating cancer described herein is not engineered to express a heterologous protein. In some embodiments, an APMV for use in a method for treating cancer is not engineered to express a cancer antigen (e.g., a tumor associated antigen). In certain embodiments, an AMPV (e.g., AMPV-1 or APMV-4) for use in a method for treating cancer is not engineered to express a heterologous viral antigen. In some embodiments, an APMV (e.g., AMPV-1 or APMV-4) for use in a method for treating cancer is not engineered to express a bacterial antigen, a fungal antigen, a protozoal antigen, or a helminth antigen. 
     5.2 VEGF-C, VEGF-D and Other VEGFR-3 Activating Agents 
     In one aspect, provided herein are VEGFR-3-activating agents. In a specific embodiment, an agent is a VEGFR-3-activating agent if it induces or enhances phosphorylation of the VEGFR-3 and induces or enhances downstream signaling events, such as, e.g., phosphorylation of serine/threonine kinases, such as, e.g., AKT, ERK1/2 or STAT3. VEGFR-3 is expressed by several immune cell types, including macrophages, blood endothelial cells, and other myeloid cells. A VEGFR-3-activating agent may promote one, two or all of the following by cells expressing VEGFR-3 (e.g., macrophages, blood endothelial cells, or other myeloid cells): (1) proliferation, (2) migration, and (3) survival. In a particular, embodiment, a VEGFR-3-activating agent promotes lymphatic endothelial cell (LEC) proliferation, migration and survival. In another embodiment, a VEGFR-3-activating agent promotes macrophage activation, polarization, proliferation, migration and/or survival. In another embodiment, a VEGFR-3-activating agent promotes myeloid cell activation, proliferation, migration and/or survival. A VEGFR-3-activating agent may be a VEGF-C agent or a VEGF-D agent. In one embodiment, a VEGFR-3-activating agent is a recombinant VEGF-C protein or a recombinant VEGF-D protein. In another embodiment, a VEGFR-3-activating agent is a nucleic acid sequence comprising a nucleotide sequence encoding a recombinant VEGF-C protein or a recombinant VEGF-D protein. The recombinant VEGF-C protein or recombinant VEGF-D protein may be derivative of naturally occurring forms of VEGF-C or VEGF-D, respectively. See this section below for examples of VEGF-C proteins, VEGF-D proteins, nucleic acid sequences encoding a VEGF-C protein, nucleic acid sequences encoding a VEGF-D protein, VEGF-C derivatives, and VEGF-D derivatives. See Table 3 below for exemplary VEGF-C and VEGF-D nucleotide and amino acid sequences. 
     VEGF-C Agent 
     In a specific embodiment, provided herein are vascular endothelial growth factor-C (VEGF-C) agents. In a specific embodiment, a VEGF-C agent is any agent that induces or enhances the expression, one or more functions, or both of VEGF-C. A VEGF-C agent may be a VEGF-C protein or derivative thereof, or a nucleic acid sequence encoding a VEGF-C protein or derivative thereof. In certain embodiments, a VEGF-C agent is conjugated, fused or linked to an antigen (e.g., bacterial antigen, a viral antigen, a fungal antigen, a protozoal antigen, a helminth antigen or a cancer antigen). In other embodiments, a VEGF-C agent is not conjugated, fused or linked to an antigen (e.g., bacterial antigen, a viral antigen, a fungal antigen, a protozoal antigen, a helminth antigen or a cancer antigen). 
     The terms “Vascular endothelial growth factor-C” and “VEGF-C” include any VEGF-C known to those of skill in the art. In a specific embodiment, VEGF-C refers to any naturally occurring form of VEGF-C. In some embodiments, VEGF-C refers to a derivative of a naturally occurring form of VEGF-C. In certain embodiments, the VEGF-C may be human, dog, cat, horse, pig, or cow VEGF-C. In a specific embodiment, the VEGF-C is human VEGF-C. GenBank™ accession number NM_005429.5 or Uniprot: P49767 provides an exemplary human VEGF-C nucleic acid sequence. After translation, the VEGF-C polypeptide typically consists of 3 domains, a central VEGF homology domain, an N-terminal domain and a C-terminal domain. GenBank™ accession number NM_005429.5 and Uniprot: P49767 provide an exemplary human VEGF-C amino acid sequence. In specific embodiments, the VEGF-C proteins are modified by post-translational processing such as signal peptide cleavage, disulfide bond formation, glycosylation (e.g., N-linked glycosylation), protease cleavage and lipid modification (e.g., S-palmitoylation). In some embodiments, the VEGF-C protein includes a signal sequence. For example, VEGF-C may undergo proteolytic maturation which includes the formation of an antiparallel homodimer linked by disulfide bonds and cleavage. Generally, the mature form of VEGF-C is composed of mostly two VEGF homology domains bound by non-covalent interactions. In certain embodiments, the VEGF-C protein does not include a signal sequence. The signal sequence can be the naturally occurring signal peptide sequence or a variant thereof. In some embodiments, the signal peptide is heterologous to a VEGF-C signal peptide (e.g., the signal sequence set forth in SEQ ID NO: 28 or 26). 
     In specific embodiments, a VEGF-C agent comprises or consists of a nucleotide sequence encoding VEGF-C. In certain embodiments, a VEGF-C agent may be a nucleic acid sequence comprising a nucleotide sequence, such as set forth in any one of SEQ ID NOs: 1-18, 29-40, 49, or 50. In a specific embodiment, a VEGF-C agent encodes human VEGF-C. In a specific embodiment, human VEGF-C comprises the amino acid sequence set forth in any one of SEQ ID NOs: 41-46. Given the degeneracy of the nucleic acid code, there are a number of different nucleic acid sequences that may encode the same VEGF-C protein. A nucleic acid sequence may encode precursor VEGF-C, pro-VEGF-C-ΔC, or mature VEGF-C (VEGF-CΔNΔC). In specific embodiments, a VEGF-C agent comprises or consists of VEGF-C protein. The VEGF-C protein may be precursor VEGF-C, pro-VEGF-C-ΔC, or mature VEGF-C (VEGF-CΔNΔC). In specific embodiments, a VEGF-C agent is a dimeric, secreted protein. In one embodiment, a VEGF-C agent comprises a full-length form of VEGF-C. In other embodiments, a VEGF-C agent comprises an unprocessed form of VEGF-C. In another embodiment, a VEGF-C agent comprises a pro-VEGF-C, which consists of two polypeptides. In another embodiment, a VEGF-C agent comprises the mature, full processed form of VEGF-C. In specific embodiments, a VEGF-C agent is one described in the Examples, infra. In some embodiments, a VEGF-C agent is a proteinaceous molecule, such as a protein encoded by the nucleotide sequence set forth in any one of SEQ ID NOs: 1-18, 29-40, 49, or 50 or a protein comprising the amino acid sequence set forth in any one of SEQ ID NOs: 19-24, 41-46, 51, or 52. In a specific embodiment, a VEGF-C agent comprises human VEGF-C. In a specific embodiment, human VEGF-C comprises the amino acid sequence set forth in any one of SEQ ID NOs: 41-46. Given the degeneracy of the nucleic acid code, there are a number of different nucleic acid sequences that may encode the same VEGF-C protein. In a specific embodiment, a VEGF-C agent is encoded by a nucleic acid sequence comprising the nucleotide sequence set forth in any one of SEQ ID NOs: 1-18, 29-40, 49, or 50. In a specific embodiment, a VEGF-C agent is encoded by a nucleic acid comprising the nucleotide sequence set forth in any one of SEQ ID NOs: 29-40. In certain embodiments, the VEGF-C agent further encodes a heterologous signal peptide, such as, e.g., set forth in SEQ ID NO: 25 or 27). 
     In a specific embodiment, a nucleic acid sequence comprising the nucleotide sequence encoding a VEGF-C agent (e.g., human VEGF-C) is codon optimized. See, e.g., Section 5.3.2.1, infra, for a discussion regarding codon optimization. In a specific embodiment, the nucleic acid sequence encoding a VEGF-C agent (e.g., human VEGF-C) comprises the nucleotide sequence set forth in any one of SEQ ID NOs: 7-21 or 35-40. In certain embodiments, a nucleic acid sequence comprising a nucleotide sequence encoding a VEGF-C agent, such as set forth in any one of SEQ ID NOs: 7-21 or 35-40, further comprises one, two, or more of the following: a regulatory sequence (e.g., a promoter, an enhancer, or both), Kozak sequences and restriction sites to facilitate cloning. 
     In a specific embodiment, a VEGF-C agent comprises murine VEGF-C. In another specific embodiment, murine VEGF-C comprises the amino acid sequence set forth in any one of SEQ ID NOs: 19-24. In another specific embodiment, the murine VEGF-C is encoded by a nucleic acid comprising the nucleotide sequence set forth in any one of SEQ ID NOs: 1-18. In another specific embodiment, a VEGF-C agent comprises canine VEGF-C. In another specific embodiment, canine VEGF-C comprises the amino acid sequence set forth in SEQ ID NO: 51 or 52. In another specific embodiment, a nucleic acid sequence comprising canine VEGF-C agent comprises the nucleotide sequence set forth in SEQ ID NO: 49 or 50. 
     In another specific embodiment, a VEGF-C agent is encoded by a nucleic acid sequence comprising the nucleotide sequence set forth in SEQ ID NO: 29, 32, or 35. In another embodiment, a VEGF-C agents comprises the nucleotide sequence set forth in SEQ ID NO: 29, 32, or 35. 
     In a specific embodiment, a nucleotide sequence or nucleic acid sequence encoding a VEGF-C agent may be a DNA molecule (e.g., cDNA or genomic DNA), an RNA molecule (e.g., mRNA), a combination of DNA and RNA molecule and a hybrid DNA/RNA molecule. In some embodiments, a nucleotide sequence or nucleic acid sequence encoding a VEGF-C agent may comprise analogs of DNA or RNA molecules. Such analogs can be generated using, for example, nucleotide analogs, which include, but are not limited to, inosine, methylcytosine, pseudouridine, or tritylated bases. Such analogs can also comprise DNA or RNA molecules comprising modified backbones that lend beneficial attributes to the molecules such as, for example, nuclease resistance or an increased ability to cross cellular membranes. The nucleic acid or nucleotide sequences can be single-stranded, double-stranded, may contain both single-stranded and double-stranded portions, and may contain triple-stranded portions. In a specific embodiment, a nucleotide sequence or nucleic acid sequence is an mRNA. In another specific embodiment, a nucleotide sequence or nucleic acid sequence is an mRNA sequence which includes nucleotide analogs (e.g., methylcytosine or pseudouridine). 
     In certain embodiments, a VEGF-C agent is a VEGF-C derivative. In a specific embodiment, a VEGF-C derivative has at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 98%, or 99% amino acid sequence identity to a VEGF-C known to those of skill in the art (e.g., any one of SEQ ID NOs: 19-24, 41-46, 51, or 52). In another specific embodiment, a VEGF-C derivative has at least 85%, 90%, 95%, 96%, 98%, or 99% amino acid sequence identity to a VEGF-C known to those of skill in the art (e.g., any one of SEQ ID NOs: 19-24, 41-46, 51, or 52). In another specific embodiment, a VEGF-C derivative has at least 90%, 95%, 96%, 98%, or 99% amino acid sequence identity to a VEGF-C known to those of skill in the art (e.g., any one of SEQ ID NOs: 19-24, 41-46, 51, or 52). In another specific embodiment, a VEGF-C derivative has at least 95%, 96%, 98%, or 99% amino acid sequence identity to a VEGF-C known to those of skill in the art (e.g., any one of SEQ ID NOs 19-24, 41-46, 51, or 52). In another embodiment, a VEGF-C derivative has at least 85%, 90%, 95%, 96%, 98% or 99% identity to native human VEGF-C (e.g., SEQ ID NO:41) or a fragment thereof (e.g., a fragment comprising the VEGF homology domain). In another embodiment, a VEGF-C derivative has at least 85%, 90%, 95%, 96%, 98% or 99% identity to native mature VEGF-C (e.g., SEQ ID NO: 44). In another embodiment, a VEGF-C derivative comprises a VEGF homology domain, wherein the VEGF homology domain has at least 85%, 90%, 95%, 96%, 98% or 99% identity to the VEGF homology domain of native VEGF-C (e.g., human VEGF-C). Methods/techniques known in the art may be used to determine sequence identity (see, e.g., “Best Fit” or “Gap” program of the Sequence Analysis Software Package, version 10; Genetics Computer Group, Inc.). In a specific embodiment, a VEGF-C derivative comprises deleted forms of a known VEGF-C (e.g., human VEGF-C), wherein up to about 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid residues are deleted from the known VEGF-C (e.g., human VEGF-C). Also provided herein are VEGF-C derivatives comprising deleted forms of a known VEGF-C, wherein about 1-3, 3-5, 5-7, 7-10, 10-15, or 15-20 amino acid residues are deleted from the known VEGF-C (e.g., human VEGF-C). Further provided herein are VEGF-C derivatives comprising altered forms of a known VEGF-C (e.g., human VEGF-C), wherein up to about 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid residues of the known VEGF-C are substituted (e.g., conservatively substituted) with other amino acids. In a specific embodiment, the known VEGF-C is human VEGF-C, such as, e.g., provided in GenBank™ accession number NM_005429.5, Uniprot: P49767, or Uniprot Q6FH59, or SEQ ID NO: 41 or 44. In some embodiments, the known VEGF-C is canine VEGF-C, such as, e.g., provided in GenBank™ accession numbers XM_S40047.6 and XM_02543044, or SEQ ID NO: 51 or 52. In some embodiments, a VEGF-C derivative comprises up to about 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 conservatively substituted amino acids. Examples of conservative amino acid substitutions include, e.g., replacement of an amino acid of one class with another amino acid of the same class. In a particular embodiment, a conservative substitution does not alter the structure or function, or both, of a polypeptide. Classes of amino acids may include hydrophobic (Met, Ala, Val, Leu, Ile), neutral hydrophylic (Cys, Ser, Thr), acidic (Asp, Glu), basic (Asn, Gln, His, Lys, Arg), conformation disruptors (Gly, Pro) and aromatic (Trp, Tyr, Phe). 
     In a specific embodiment, a VEGF-C derivative is at least 80%, 85%, 90%, 95%, 98%, or 99% or is 80% to 85%, 80% to 90%, 80% to 95%, 90% to 95%, 85% to 99%, or 95% to 99% identical (e.g., sequence identity) to a native VEGF-C (e.g., human VEGF-C). In a specific embodiment, a VEGF-C derivative is at least 90%, 95%, 98%, or 99% or is 90% to 95%, 90% to 99%, 95% to 98%, or 95% to 99% identical (e.g., sequence identity) to a native VEGF-C (e.g., human VEGF-C). In another specific embodiment, a VEGF-C derivative is a polypeptide encoded by a nucleic acid sequence that is at least 80%, 85%, 90%, 95%, 98%, or 99% or is 80% to 85%, 80% to 90%, 80% to 95%, 90% to 95%, 85% to 99%, or 95% to 99% identical (e.g., sequence identity) to a nucleic acid sequence encoding a native VEGF-C. In another specific embodiment, a VEGF-C is a polypeptide encoded by a nucleic acid sequence that is at least 90%, 95%, 98%, or 99% or is 90% to 95%, 90% to 99%, 95% to 98%, or 95% to 99% identical (e.g., sequence identity) to a nucleic acid sequence encoding a native VEGF-C. In a specific embodiment, the native VEGF-C is human VEGF-C, such as, e.g., provided in GenBank™ accession number NM_005429.5, Uniprot: P49767, or Uniprot Q6FH59, or SEQ ID NO: 41 or 44. In some embodiments, the native VEGF-C is canine VEGF-C, such as, e.g., provided in GenBank™ accession numbers XM_S40047.6 and XM_02543044, or SEQ ID NO: 51 or 52. In another specific embodiment, a VEGF-C derivative contains 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more, or 2 to 5, 2 to 10, 5 to 10, 5 to 15, 5 to 20, 10 to 15, or 15 to 20 amino acid mutations (i.e., additions, deletions, substitutions or any combination thereof) relative to a native VEGF-C (e.g., human VEGF-C). In another specific embodiment, a VEGF-C derivative is a polypeptide encoded by nucleic acid sequence that can hybridize under high, moderate or typical stringency hybridization conditions to a nucleic acid sequence encoding a native VEGF-C (e.g., human VEGF-C). Hybridization conditions are known to one of skill in the art (see, e.g., U.S. Patent Application No. 2005/0048549 at, e.g., paragraphs 72 and 73). In another specific embodiment, a VEGF-C derivative is a polypeptide encoded by a nucleic acid sequence that can hybridize under high, moderate or typical stringency hybridization conditions to a nucleic acid sequence encoding a fragment of a native VEGF-C (e.g., human VEGF-C) of at least 10 contiguous amino acids, at least 12 contiguous amino acids, at least 15 contiguous amino acids, at least 20 contiguous amino acids, at least 30 contiguous amino acids, at least 40 contiguous amino acids, at least 50 contiguous amino acids, at least 75 contiguous amino acids, at least 100 contiguous amino acids, at least 125 contiguous amino acids, at least 150 contiguous amino acids, or 10 to 20, 20 to 50, 25 to 75, 25 to 100, 25 to 150, 50 to 75, 50 to 100, 75 to 100, 50 to 150, 75 to 150, 100 to 150, or 100 to 200 contiguous amino acids. In another specific embodiment, a VEGF-C derivative is a fragment of a native VEGF-C (e.g., human VEGF-C). In another specific embodiment, a VEGF-C derivative comprises a fragment of human VEGF-C (e.g., a fragment of SEQ ID NO: 41 or 44). In another specific embodiment, a VEGF-C derivative comprises a fragment of a human VEGF-C (e.g., SEQ ID NO: 41 or 44), wherein the fragment comprises the VEGF homology domain. In a specific embodiment, a VEGF-D derivative is a fragment of a native VEGF-D (e.g., a human VEGF-D) that comprises the VEGF homology domain. In a specific embodiment, a fragment of native VEGF-C retains the ability to bind to VEGFR-3, induces phosphorylation of VEGFR-3 and induces downstream signaling events, such as, e.g., phosphorylation of serine/threonine kinases, such as, e.g., AKT, ERK 1/2, or Stat 3. VEGF-C derivatives also include polypeptides that comprise the amino acid sequence of a naturally occurring mature form of VEGF-C and a heterologous amino acid sequence. VEGF-C derivatives also include polypeptides that comprise the amino acid sequence of a naturally occurring mature form of VEGF-C and a heterologous signal peptide amino acid sequence (e.g., the signal peptide set forth in SEQ ID NO: 28 or 26). In some embodiments, the VEGF-C derivative comprises (i) a polypeptide that comprises the amino acid sequence of a naturally occurring mature form of VEGF-C and (ii) a heterologous amino acid sequence (e.g., a heterologous signal peptide, such as, e.g., the signal peptide for  Gaussia  luciferase (e.g., SEQ ID NO: 28 or 26)). In addition, VEGF-C derivatives include polypeptides that have been chemically modified by, e.g., glycosylation, acetylation, pegylation, phosphorylation, amidation, derivitization by known protecting/blocking groups, proteolytic cleavage, linkage to a cellular ligand or other protein moiety, etc. Further, VEGF-C derivatives include polypeptides comprising one or more non-classical amino acids. 
     In a specific embodiment, a VEGF-C derivative comprises a VEGF-C amino acid sequence (e.g., SEQ ID NO: 41) with an amino acid substitution of Cys156Ser or Cys137Ala. See, e.g., Kajiya K et al., 2009, J Invest Dermatol. 129:1292-8 and Leppanen et al., 2010, Proc Natl Acad Sci USA. 107(6):2425-30 for a description of such forms of VEGF-C. In certain embodiments, a VEGF-C derivative comprises the nucleotide sequence of SEQ ID NO: 30, 31, 33, 34, 36, 37, 39, or 40. In some embodiments, a VEGF-C derivative is mature VEGF-C Cys156Ser (e.g., SEQ ID NO: 45). In other embodiments, a VEGF-C derivative is human VEGF-C Cys137Ala (e.g., SEQ ID NO: 46). 
     In a specific embodiment, a VEGF-C derivative binds to VEGFR-3 but not VEGFR-2. In a specific embodiment, a VEGF-C derivative binds to VEGFR-3 and induces phosphorylation of VEGFR-3 and activates downstream signaling, including but not limited to phosphorylation of serine/threonine kinases, such as AKT, ERT1/2 and Stat3. In specific embodiments, the VEGF-C derivative retains one, two, or more, or all of the functions of the native VEGF-C (e.g., human VEGF-C) from which it was derived. Examples of functions of VEGF-C include lymphangiogenesis, lymphatic endothelial proliferation and migration, lymphatic permeability and contractility, angiogenesis, macrophage recruitment and immunomodulation. Tests for determining whether or not a VEGF-C derivative retains one or more functions of the native VEGF-C (e.g., human VEGF-C) from which it was derived are known to one of skill in the art and examples are provided herein. 
     In a specific embodiment, a VEGF-C agent comprises the nucleotide sequence set forth in any one of SEQ ID NOs: 1-18, 29-40, 49, or 50 or is encoded by the nucleotide sequence set forth in any one of SEQ ID NOs: 1-18, 29-40, 49, or 50. In a specific embodiment, a VEGF-C agent comprises the amino acid sequence set forth in any one of SEQ ID NOs: 19-24, 41-46, 51, or 52. Examples of VEGF-C sequences which may be used in accordance with the methods described herein are provided in Table 3, infra. 
     Techniques known to one of skill in the art may be used to produce a VEGF-C agent. For example, standard methods in molecular biology are described Sambrook, Fritsch and Maniatis (1982 &amp; 1989 2nd Edition, 2001 3rd Edition) Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.; Sambrook and Russell (2001) Molecular Cloning, 3rd ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.; Wu (1993) Recombinant DNA, Vol. 217, Academic Press, San Diego, Calif.). Standard methods also appear in Ausbel, et al. (2001) Current Protocols in Molecular Biology, Vols. 1-4, John Wiley and Sons, Inc. New York, N.Y., which describes cloning in bacterial cells and DNA mutagenesis (Vol. 1), cloning in mammalian cells and yeast (Vol. 2), glycoconjugates and protein expression (Vol. 3), and bioinformatics (Vol. 4). In a specific embodiment, a VEGFR-3-activating agent is recombinantly produced. In another specific embodiment, a VEGF-C agent is recombinantly produced. 
     Methods for protein purification including immunoprecipitation, chromatography, electrophoresis, centrifugation, and crystallization are described (Coligan, et al. (2000) Current Protocols in Protein Science, Vol. 1, John Wiley and Sons, Inc., New York). Chemical analysis, chemical modification, post-translational modification, production of fusion proteins, glycosylation of proteins are described (see, e.g., Coligan, et al. (2000) Current Protocols in Protein Science, Vol. 2, John Wiley and Sons, Inc., New York; Ausubel, et al. (2001) Current Protocols in Molecular Biology, Vol. 3, John Wiley and Sons, Inc., NY, NY, pp. 16.0.5-16.22.17; Sigma-Aldrich, Co. (2001) Products for Life Science Research, St. Louis, Mo.; pp. 45-89; Amersham Pharmacia Biotech (2001) BioDirectory, Piscataway, N.J., pp. 384-391). In a specific embodiment, a VEGFR-3 activating agent is isolated. In another specific embodiment, a VEGF-C agent is isolated. 
     In a specific embodiment, a protein is isolated when substantially free of contaminating materials from the natural source, e.g., soil particles, minerals, chemicals from the environment, and/or cellular materials from the natural source, such as but not limited to cell debris, cell wall materials, membranes, organelles, the bulk of the nucleic acids, carbohydrates, proteins, and/or lipids present in cells. Thus, a protein that is isolated includes preparations of a polypeptide having less than about 30%, 20%, 10%, 5%, 2%, or 1% (by dry weight) of cellular materials and/or contaminating materials. In some embodiments, a chemically synthesized polypeptide is isolated when substantially free of chemical precursors or other chemicals which are involved in the syntheses of the polypeptide. The term “substantially free of chemical precursors or other chemicals” includes preparations in which the amino acid sequence is separated from chemical precursors or other chemicals which are involved in the synthesis of the amino acid sequence. In specific embodiments, such preparations of the amino acid sequence have less than about 50%, 30%, 20%, 10%, 5% (by dry weight) of chemical precursors or compounds other than the amino acid sequence of interest. 
     In certain embodiments, an “isolated” nucleic acid sequence refers to a nucleic acid molecule which is separated from other nucleic acid molecules which are present in the natural source of the nucleic acid. In other words, the isolated nucleic acid sequence can comprise heterologous nucleic acids that are not associated with it in nature. In other embodiments, an “isolated” nucleic acid sequence, such as a cDNA or RNA sequence, can be substantially free of other cellular material, or culture medium when produced by recombinant techniques, or substantially free of chemical precursors or other chemicals when chemically synthesized. The term “substantially free of cellular material” includes preparations of nucleic acid sequences in which the nucleic acid sequence is separated from cellular components of the cells from which it is isolated or recombinantly produced. Thus, nucleic acid sequence that is substantially free of cellular material includes preparations of nucleic acid sequence having less than about 30%, 20%, 10%, or 5% (by dry weight) of other nucleic acids. The term “substantially free of culture medium” includes preparations of nucleic acid sequence in which the culture medium represents less than about 50%, 20%, 10%, or 5% of the volume of the preparation. The term “substantially free of chemical precursors or other chemicals” includes preparations in which the nucleic acid sequence is separated from chemical precursors or other chemicals which are involved in the synthesis of the nucleic acid sequence. In specific embodiments, such preparations of the nucleic acid sequence have less than about 50%, 30%, 20%, 10%, 5% (by dry weight) of chemical precursors or compounds other than the nucleic acid sequence of interest. 
     VEGF-D Agent 
     In a specific embodiment, provided herein are vascular endothelial growth factor-D (VEGF-D) agents. In a specific embodiment, a VEGF-D agent is any agent that induces or enhances the expression, one or more functions, or both of VEGF-D. A VEGF-D agent may be a VEGF-D protein or derivative thereof, or a nucleic acid sequence encoding a VEGF-D protein or derivative thereof. In certain embodiments, a VEGF-D agent is conjugated, fused or linked to an antigen (e.g., bacterial antigen, a viral antigen, a fungal antigen, a protozoal antigen, a helminth antigen or a cancer antigen). In other embodiments, a VEGF-D agent is not conjugated, fused or linked to an antigen (e.g., bacterial antigen, a viral antigen, a fungal antigen, a protozoal antigen, a helminth antigen or a cancer antigen). 
     The terms “Vascular endothelial growth factor-D” and “VEGF-D” include any VEGF-D known to those of skill in the art. In a specific embodiment, VEFG-D refers to any naturally occurring form of VEGF-D. In some embodiments, VEGF-D refers to a derivative of a naturally occurring form of VEGF-D. In certain embodiments, the VEGF-D may be human, dog, cat, horse, pig, or cow VEGF-D. In a specific embodiment, the VEGF-D is human VEGF-D. Uniprot O43915 provides an exemplary human VEGF-D nucleic acid sequence. After translation, the VEGF-D polypeptide generally consists of 3 domains, a central VEGF homology domain, an N-terminal domain and a C-terminal domain. Uniprot O43915 provides an exemplary human VEGF-D amino acid sequence. In specific embodiments, the VEGF-D proteins are modified by post-translational processing such as signal peptide cleavage, disulfide bond formation, glycosylation (e.g., N-linked glycosylation), protease cleavage and lipid modification (e.g., S-palmitoylation). For example, VEGF-D may undergo proteolytic maturation which includes the formation of an antiparallel homodimer linked by disulfide bonds and cleavage. Generally, the mature form of VEGF-D is composed of mostly two VEGF homology domains bound by non-covalent interactions. In some embodiments, VEGF-D protein includes a signal sequence. In other embodiments, VEGF-D protein does not include a signal sequence. The signal sequence can be the naturally occurring signal peptide sequence or a variant thereof. In some embodiments, the signal peptide is a VEGF-D signal peptide. In some embodiments, the signal peptide is heterologous to a VEGF-D signal peptide (e.g., a signal peptide set forth in SEQ ID NO: 28 or 26). 
     In specific embodiments, a VEGF-D agent comprises or consists of a nucleotide sequence encoding VEGF-D. In certain embodiments, a VEGF-D agent may be a nucleic acid sequence comprising a nucleotide sequence, such as set forth in any one of SEQ ID NOs: 96-98. In a specific embodiment, a VEGF-D agent encodes human VEGF-D. In a specific embodiment, human VEGF-D comprises the amino acid sequence set forth in SEQ ID NO: 101-104. Given the degeneracy of the nucleic acid code, there are a number of different nucleic acid sequences that may encode the same VEGF-D protein. A nucleic acid sequence may encode precursor VEGF-D, pro-VEGF-D-ΔC, or mature VEGF-D (VEGF-DΔNΔC). 
     In specific embodiments, a VEGF-D agent comprises or consists of VEGF-D protein. The VEGF-D protein may be precursor VEGF-D, pro-VEGF-D-ΔC, or mature VEGF-D (VEGF-DΔNΔC). In specific embodiments, a VEGF-D agent is a dimeric, secreted protein. In one embodiment, a VEGF-D agent comprises a pro-VEGF-D, which consists of two polypeptides. In another embodiment, a VEGF-D agent comprises the mature, full processed form of VEGF-D. In certain embodiments, a VEGF-D agent is a proteinaceous molecule, such as a protein encoded by the nucleotide sequence set forth in any one of SEQ ID NOs: 96-98, or a protein comprising the amino acid sequence set forth in any one of SEQ ID NO: 99-104. In a specific embodiment, a VEGF-D agent comprises human VEGF-D. In a specific embodiment, human VEGF-D comprises the amino acid sequence set forth in SEQ ID NO: 101-104. In another specific embodiment, human VEGF-D is encoded by a nucleic acid sequence comprising the nucleotide sequence set forth in SEQ ID NO: 96. Given the degeneracy of the nucleic acid code, there are a number of different nucleic acid sequences that may encode the same VEGF-D protein. In a specific embodiment, a VEGF-D agent is encoded by a nucleic acid sequence comprising the nucleotide sequence set forth in any one of SEQ ID NOs: 96-98. 
     In a specific embodiment, a VEGF-D agent comprises canine VEGF-D. In a specific embodiment, canine VEGF-D comprises the amino acid sequence set forth in SEQ ID NO: 99 or 100. In a specific embodiment, canine VEGF-D is encoded by a nucleic acid sequence comprising the nucleotide sequence set forth in SEQ ID NO: 97 or 98. 
     In a specific embodiment, a VEGF-D agent comprises human VEGF-D. In a specific embodiment, human VEGF-D comprises the amino acid sequence set forth in SEQ ID NO: 101-104. In a specific embodiment, human VEGF-D is encoded by a nucleic acid sequence comprising the nucleotide sequence set forth in SEQ ID NO: 96. 
     In a specific embodiment, a nucleic acid sequence comprising the nucleotide sequence encoding a VEGF-D agent (e.g., human VEGF-D) is codon optimized. See, e.g., Section 5.3.2.1, infra, for a discussion regarding codon optimization. In certain embodiments, a nucleic acid sequence comprising a nucleotide sequence encoding a VEGF-D protein, such as set forth in any one of SEQ ID NOs: 96-98, further comprises one, two, or more of the following: a regulatory sequence (e.g., a promoter, an enhancer, or both), Kozak sequences and restriction sites to facilitate cloning. 
     In a specific embodiment, a nucleotide sequence or nucleic acid sequence encoding a VEGF-D agent may be a DNA molecule (e.g., cDNA or genomic DNA), an RNA molecule (e.g., mRNA), a combination of DNA and RNA molecule and a hybrid DNA/RNA molecule. In some embodiments, a nucleotide sequence or nucleic acid sequence encoding a VEGF-D agent may comprise analogs of DNA or RNA molecules. Such analogs can be generated using, for example, nucleotide analogs, which include, but are not limited to, inosine methylcytosine, pseudouridine, or tritylated bases. Such analogs can also comprise DNA or RNA molecules comprising modified backbones that lend beneficial attributes to the molecules such as, for example, nuclease resistance or an increased ability to cross cellular membranes. The nucleic acid or nucleotide sequences can be single-stranded, double-stranded, may contain both single-stranded and double-stranded portions, and may contain triple-stranded portions. In a specific embodiment, a nucleotide sequence or nucleic acid sequence is an mRNA. In another specific embodiment, a nucleotide sequence or nucleic acid sequence is an mRNA sequence which includes nucleotide analogs (e.g., methylcytosine or pseudouridine). 
     In certain embodiments, a VEGF-D agent is a VEGF-D derivative. In a specific embodiment, a VEGF-D derivative has at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 98%, or 99% amino acid sequence identity to a VEGF-D known to those of skill in the art (e.g., any one of SEQ ID NO: 99-104). In another specific embodiment, a VEGF-D derivative has at least 85%, 90%, 95%, 96%, 98%, or 99% amino acid sequence identity to a VEGF-D known to those of skill in the art (e.g., any one of SEQ ID NO: 99-104). In another specific embodiment, a VEGF-D derivative has at least 90%, 95%, 96%, 98%, or 99% amino acid sequence identity to a VEGF-D known to those of skill in the art (e.g., any one of SEQ ID NO: 99-104). In another specific embodiment, a VEGF-D derivative has at least 95%, 96%, 98%, or 99% amino acid sequence identity to a VEGF-D known to those of skill in the art (e.g., any one of SEQ ID NO: 99-104). In another embodiment, a VEGF-D derivative has at least 85%, 90%, 95%, 96%, 98% or 99% identity to native human VEGF-D (e.g., SEQ ID NO: 104) or a fragment thereof (e.g., a fragment comprising the VEGF homology domain). In another embodiment, a VEGF-D derivative has at least 85%, 90%, 95%, 96%, 98% or 99% identity to native mature VEGF-D (e.g., SEQ ID NO: 101). In another embodiment, a VEGF-D derivative comprises a VEGF homology domain, wherein the VEGF homology domain has at least 85%, 90%, 95%, 96%, 98% or 99% identity to the VEGF homology domain of native VEGF-D. Methods/techniques known in the art may be used to determine sequence identity (see, e.g., “Best Fit” or “Gap” program of the Sequence Analysis Software Package, version 10; Genetics Computer Group, Inc.). In a specific embodiment, a VEGF-D derivative comprises deleted forms of a known VEGF-D (e.g., human VEGF-D), wherein up to about 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid residues are deleted from the known VEGF-D (e.g., human VEGF-D). Also provided herein are VEGF-D derivatives comprising deleted forms of a known VEGF-D, wherein about 1-3, 3-5, 5-7, 7-10, 10-15, or 15-20 amino acid residues are deleted from the known VEGF-D (e.g., human VEGF-D). Further provided herein are VEGF-D derivatives comprising altered forms of a known VEGF-D (e.g., human VEGF-D), wherein up to about 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid residues of the known VEGF-D are substituted (e.g., conservatively substituted) with other amino acids. In a specific embodiment, the known VEGF-D is human VEGF-D, such as, e.g., provided in Uniprot O43915. In certain embodiments, the known VEGF-D, is canine VEGF-D, such, e.g., provided in GenBank™ accession number XM_548869.5 or XM_025437083. In some embodiments, a VEGF-D derivative comprises up to about 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 conservatively substituted amino acids. Examples of conservative amino acid substitutions include, e.g., replacement of an amino acid of one class with another amino acid of the same class. In a particular embodiment, a conservative substitution does not alter the structure or function, or both, of a polypeptide. Classes of amino acids may include hydrophobic (Met, Ala, Val, Leu, Ile), neutral hydrophylic (Cys, Ser, Thr), acidic (Asp, Glu), basic (Asn, Gln, His, Lys, Arg), conformation disruptors (Gly, Pro) and aromatic (Trp, Tyr, Phe). 
     In a specific embodiment, a VEGF-D derivative is at least 80%, 85%, 90%, 95%, 98%, or 99% or is 80% to 85%, 80% to 90%, 80% to 95%, 90% to 95%, 85% to 99%, or 95% to 99% identical (e.g., sequence identity) to a native VEGF-D (e.g., human VEGF-D). In a specific embodiment, a VEGF-D derivative is at least 90%, 95%, 98%, or 99% or is 90% to 95%, 90% to 99%, 95% to 98%, or 95% to 99% identical (e.g., sequence identity) to a native VEGF-D (e.g., human VEGF-D). In another specific embodiment, a VEGF-D derivative is a polypeptide encoded by a nucleic acid sequence that is at least 80%, 85%, 90%, 95%, 98%, or 99% or is 80% to 85%, 80% to 90%, 80% to 95%, 90% to 95%, 85% to 99%, or 95% to 99% identical (e.g., sequence identity) to a nucleic acid sequence encoding a native VEGF-D. In another specific embodiment, a VEGF-D is a polypeptide encoded by a nucleic acid sequence that is at least 90%, 95%, 98%, or 99% or is 90% to 95%, 90% to 99%, 95% to 98%, or 95% to 99% identical (e.g., sequence identity) to a nucleic acid sequence encoding a native VEGF-D. In a specific embodiment, the native VEGF-D is human VEGF-D, such as, e.g., provided in Uniprot O43915. In other embodiments, the native VEGF-D is a canine VEGF-D, such as e.g., provided in GenBank™ accession numbers XM_548869.5 or XM_025437083. In another specific embodiment, a VEGF-D derivative contains 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more, or 2 to 5, 2 to 10, 5 to 10, 5 to 15, 5 to 20, 10 to 15, or 15 to 20 amino acid mutations (i.e., additions, deletions, substitutions or any combination thereof) relative to a native VEGF-D (e.g., human VEGF-D). In another specific embodiment, a VEGF-D derivative is a polypeptide encoded by nucleic acid sequence that can hybridize under high, moderate or typical stringency hybridization conditions to a nucleic acid sequence encoding a native VEGF-D (e.g., human VEGF-D). Hybridization conditions are known to one of skill in the art (see, e.g., U.S. Patent Application No. 2005/0048549 at, e.g., paragraphs 72 and 73). In another specific embodiment, a VEGF-D derivative is a polypeptide encoded by a nucleic acid sequence that can hybridize under high, moderate or typical stringency hybridization conditions to a nucleic acid sequence encoding a fragment of a native VEGF-D (e.g., human VEGF-D) of at least 10 contiguous amino acids, at least 12 contiguous amino acids, at least 15 contiguous amino acids, at least 20 contiguous amino acids, at least 30 contiguous amino acids, at least 40 contiguous amino acids, at least 50 contiguous amino acids, at least 75 contiguous amino acids, at least 100 contiguous amino acids, at least 125 contiguous amino acids, at least 150 contiguous amino acids, or 10 to 20, 20 to 50, 25 to 75, 25 to 100, 25 to 150, 50 to 75, 50 to 100, 75 to 100, 50 to 150, 75 to 150, 100 to 150, or 100 to 200 contiguous amino acids. In another specific embodiment, a VEGF-D derivative is a fragment of a native VEGF-D (e.g., human VEGF-D). In another specific embodiment, a VEGF-D derivative comprises a fragment of human VEGF-D (e.g., a fragment of any one of SEQ ID Nos: 100-104). In a specific embodiment, a VEGF-D derivative is a fragment of a native VEGF-D (e.g., a human VEGF-D) that comprises the VEGF homology domain. In another specific embodiment, a VEGF-D derivative comprises a fragment of a human VEGF-D (e.g., any one of SEQ ID NOs: 100-104), wherein the fragment comprises the VEGF homology domain. In a specific embodiment, a fragment of native VEGF-D retains the ability to bind to VEGFR-3, induces phosphorylation of VEGFR-3 and induces downstream signaling events, such as, e.g., phosphorylation of serine/threonine kinases, such as, e.g., AKT, ERK 1/2, or Stat 3. 
     VEGF-D derivatives also include polypeptides that comprise the amino acid sequence of a naturally occurring mature form of VEGF-D and a heterologous amino acid sequence. VEGF-D derivatives also include polypeptides that comprise the amino acid sequence of a naturally occurring mature form of VEGF-D and a heterologous signal peptide amino acid sequence. In some embodiments, the VEGF-D derivative comprises (i) a polypeptide that comprises the amino acid sequence of a naturally occurring mature form of VEGF-D and (ii) a heterologous peptide amino acid sequence (e.g., a heterologous signal peptide, such as, e.g., the signal peptide for  Gaussia  luciferase (e.g., SEQ ID NO: 28) or the signal peptide for IgG light chain signal peptide (e.g., SEQ ID NO: 26). In addition, VEGF-D derivatives include polypeptides that have been chemically modified by, e.g., glycosylation, acetylation, pegylation, phosphorylation, amidation, derivitization by known protecting/blocking groups, proteolytic cleavage, linkage to a cellular ligand or other protein moiety, etc. Further, VEGF-D derivatives include polypeptides comprising one or more non-classical amino acids. 
     In a specific embodiment, a VEGF-D derivative binds to VEGFR-3 and induces phosphorylation of VEGFR-3 and activates downstream signaling, e.g., phosphorylation of serine/threonine kinases, such as AKT, ERT1/2 or Stat3. In specific embodiments, the VEGF-D derivative retains one, two, or more, or all of the functions of the native VEGF-D (e.g., human VEGF-D) from which it was derived. Examples of functions of VEGF-D include lymphatic endothelial proliferation and migration, lymphatic permeability and contractility, angiogenesis, and remodeling of lymphatic and blood vessels. Tests for determining whether or not a VEGF-D derivative retains one or more functions of the native VEGF-D (e.g., human VEGF-D) from which it was derived are known to one of skill in the art and examples are provided herein. In a specific embodiment, a VEGF-D derivative binds to VEGFR-3 but not VEGFR-2/. 
     In a specific embodiment, a VEGF-D agent comprises the amino acid sequence set forth in any one of SEQ ID NOs: 99-104, or is encoded by the nucleotide sequence set forth in any one of SEQ ID NOs: 96-98. Examples of VEGF-D sequences which may be used in accordance with the methods described herein are provided in Table 3, infra. 
     Techniques known to one of skill in the art may be used to produce a VEGF-D agent. For example, standard methods in molecular biology are described Sambrook, Fritsch and Maniatis (1982 &amp; 1989 2nd Edition, 2001 3rd Edition) Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.; Sambrook and Russell (2001) Molecular Cloning, 3rd ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.; Wu (1993) Recombinant DNA, Vol. 217, Academic Press, San Diego, Calif.). Standard methods also appear in Ausbel, et al. (2001) Current Protocols in Molecular Biology, Vols. 1-4, John Wiley and Sons, Inc. New York, N.Y., which describes cloning in bacterial cells and DNA mutagenesis (Vol. 1), cloning in mammalian cells and yeast (Vol. 2), glycoconjugates and protein expression (Vol. 3), and bioinformatics (Vol. 4). In another specific embodiment, a VEGF-D agent is recombinantly produced. 
     Methods for protein purification including immunoprecipitation, chromatography, electrophoresis, centrifugation, and crystallization are described (Coligan, et al. (2000) Current Protocols in Protein Science, Vol. 1, John Wiley and Sons, Inc., New York). Chemical analysis, chemical modification, post-translational modification, production of fusion proteins, glycosylation of proteins are described (see, e.g., Coligan, et al. (2000) Current Protocols in Protein Science, Vol. 2, John Wiley and Sons, Inc., New York; Ausubel, et al. (2001) Current Protocols in Molecular Biology, Vol. 3, John Wiley and Sons, Inc., NY, NY, pp. 16.0.5-16.22.17; Sigma-Aldrich, Co. (2001) Products for Life Science Research, St. Louis, Mo.; pp. 45-89; Amersham Pharmacia Biotech (2001) BioDirectory, Piscataway, N.J., pp. 384-391). In another specific embodiment, a VEGF-D agent is isolated. 
     5.3 Recombinant Oncolytic Viruses 
     In one aspect, provided herein are recombinant viruses that provided herein are recombinant viruses comprising a genome, wherein the genome comprises a transgene comprising a nucleotide sequence encoding a VEGFR-3 activating agent. In some embodiments, the virus can be any virus known in the art, including, e.g., an adeno-associated virus (“AAV”; e.g., AAV1-AAV9). In other embodiments, the virus is not an adeno-associate virus (e.g., is not AAV1-AAV9). In one aspect, provided herein are recombinant oncolytic viruses comprising a genome, wherein the genome comprises a transgene comprising a nucleotide sequence encoding a VEGFR-3-activating agent. In one embodiment, a VEGFR-3-activating agent is a VEGF-C protein or a VEGF-D protein. In another embodiment, a VEGFR-3-activating agent is a nucleic acid sequence comprising a nucleotide sequence encoding a VEGF-C protein or a VEGF-D protein. The VEGF-C protein or VEGF-D protein may be derivatives of VEGF-C or VEGF-D, respectively. See Section 5.2 and 5.3.2 for examples of VEGF-C proteins, VEGF-D proteins, nucleic acid sequences encoding a VEGF-C protein, and nucleic acid sequences encoding a VEGF-D protein, VEGF-C derivatives, and VEGF-D derivatives. 
     In another aspect, provided herein are recombinant oncolytic viruses comprising a genome, wherein the genome comprises a transgene comprising a nucleotide sequence encoding a VEGF-C agent, a VEGF-D agent, or both. In another aspect, provided herein are recombinant oncolytic viruses comprising a genome, wherein the genome comprises a transgene comprising a nucleotide sequence encoding a VEGF-C agent and a transgene comprising a nucleotide sequence encoding a VEGF-D agent. See, e.g., Section 5.3 and Section 6 for examples of transgenes which may be incorporated into the genome of an oncolytic virus. See e.g., section 5.1 and 6 for examples of viruses which may be engineered to encode/express a transgene. In some embodiments, recombinant oncolytic virus is a parovirus (e.g., an autonomous parvovirus), a myxoma virus, an avian paramyxovirus (e.g., Newcastle disease virus or APMV-4), a reovirus, or Seneca valley virus. In one embodiment, the recombinant oncolytic virus is wild-type parvovirus H1 (ParvOryx). In another embodiment, the recombinant oncolytic virus is Vesicular stomatitis virus. In another embodiment, the recombinant oncolytic virus is an avian paramyxovirus. See Sections 5.1.1 and 5.3 (including 5.3.1.1) regarding avian paramyxoviruses. In some embodiments, the recombinant oncolytic virus is a genetically engineered influenza virus, measles virus, poliovirus, vaccinia virus, poxvirus, picornavirus, alphavirus, retrovirus, rhabdovirus, reovirus, adenovirus, herpes simplex virus, or vesicular stomatitis virus. In a specific embodiment, such viruses are attenuated. In one embodiment, the recombinant oncolytic virus is an E1A/E1B-deleted adenovirus (ONYX015) (see, e.g., Cohen and Rudin, 2001, Curr. Opin. Investig. Drugs 2(12): 1770-1775, which is incorporated by reference in its entirety, for information regarding ONYX015. In another embodiment, the recombinant oncolytic virus is the adenovirus is H101, a conditionally replicative adenovirus, was generated by both E1B and E3 gene deletion (see, e.g., Kasuya et al., 2007, Curr Cancer Drug Targets. 7:123-125, which is incorporated by reference in its entirety, for information regarding H101). In another embodiment, the recombinant oncolytic virus is adenovirus known as Delta-24-RGD (DNX-2401). In another embodiment, the recombinant oncolytic virus is an attenuated influenza virus (e.g., an influenza virus comprising a truncated NS1 protein, such as described in U.S. Pat. Nos. 10,098,945; 8,057,803; 8,124,101; 8,137,676; 6,866,853; 6,669,943; 6,468,544; 8,137,676; and 9,387,240, each of which is incorporated herein by reference in its entirety). In another embodiment, the recombinant oncolytic virus is HSV1716 (Seprehvir®). In another embodiment, the recombinant oncolytic virus is G207. In another embodiment, the recombinant oncolytic virus is Pelareorep (Reolysin®). 
     In certain embodiments, a recombinant oncolytic viruses comprises a genome, wherein the genome comprises a first transgene comprising a nucleotide sequence encoding a VEGF-C agent, a VEGF-D agent, or both, and a second transgene comprising a nucleotide sequence encoding a heterologous protein. In some embodiments, a recombinant oncolytic viruses comprises a genome, wherein the genome comprises a first transgene comprising a nucleotide sequence encoding a VEGF-C agent, a second transgene comprising a nucleotide sequence encoding VEGF-D, and a third transgene comprising a nucleotide sequence encoding a heterologous protein. In certain aspects, provided herein is a combination of oncolytic viruses comprising two, three or more oncolytic viruses. In some embodiments, a first recombinant oncolytic virus comprises a first genome, wherein the first genome comprises a first transgene comprising a nucleotide sequence encoding a VEGF-C agent, a second recombinant oncolytic virus comprises a second genome, wherein the second genome comprises a second transgene comprising a nucleotide sequence encoding VEGF-D, and a third recombinant oncolytic virus comprises a third genome, wherein the third genome comprises a third transgene comprising a nucleotide sequence encoding a heterologous protein. In some embodiments, the combination of oncolytic viruses consists of the first and second oncolytic viruses. In some embodiments, the combination of oncolytic viruses consists of the first and third oncolytic viruses. In some embodiments, the combination of oncolytic viruses consists of the first, second and third oncolytic viruses. For example, an oncolytic virus may be engineered to express a checkpoint inhibitor (e.g., an antibody that specifically binds to PD-1 and blocks binding of PD-1 to PDL1, PDL2 or both, such as pembrolizumab or nivolumab; an antibody that specifically binds to PDL1 and blocks binding of PDL1 to PD1, CD80 or both, such as atezolizumab, durvalumab, or cemiplimab; and an antibody that specifically binds to CLTA-4 and block the interaction of CTLA-4 with its ligands B7.1 and B7.2, such as ipilimumab or tremelimumab and an antibody that specifically binds to TIM3); a cytokine (e.g., IL-2, IL-12, IL-15, IFN alpha/beta, 41-BB, CD40L, Flt3L, CCL3, CCL5, GM-CSF, etc.); an agonist of a co-stimulatory molecule (e.g., an agonist of ICOS, ICOS-L, OX40, OX40L, etc.); or a cancer antigen (e.g., a tumor associated antigen). See, e.g., Section 5.7.2 for examples of checkpoint inhibitors and agonists of co-stimulatory molecules. In some embodiments, the recombinant oncolytic virus is pexastimogene devacirepvec (Pexa-Vec, formerly named JX-594), ONCOS (adeno Δ24-RGD-GM-CSF insertion), herpes virus OrienX010, ICOVIR-5, Talimogene Laherparepvec (T-VEC, Imlygic®), VV JX-594, Ad Ad5/3-D24-GMCSF, or CG0070. 
     In certain embodiments in which a recombinant oncolytic viruses comprises a genome, wherein the genome comprises a first transgene comprising a nucleotide sequence encoding a VEGF-C agent, a VEGF-D agent, or both, or a first transgene comprising a nucleotide sequence encoding a VEGF-C agent and a second transgene comprising a nucleotide sequence encoding a VEGF-D agent, the genome does not further comprise a transgene comprising a nucleotide sequence encoding a heterologous protein. In some embodiments in which a recombinant oncolytic viruses comprises a genome, wherein the genome comprises a first transgene comprising a nucleotide sequence encoding a VEGF-C agent, a VEGF-D agent, or both, or a first transgene comprising a nucleotide sequence encoding a VEGF-C agent and a second transgene comprising a nucleotide sequence encoding a VEGF-D agent, the genome does not further comprise a transgene comprising a nucleotide sequence encoding a heterologous antigen (e.g., a bacterial antigen, a viral antigen, a fungal antigen, a protozoal antigen, a helminth antigen or a cancer antigen). In certain embodiments in which a recombinant oncolytic viruses comprises a genome, wherein the genome comprises a first transgene comprising a nucleotide sequence encoding a VEGF-C agent, a VEGF-D agent, or both, or a first transgene comprising a nucleotide sequence encoding a VEGF-C agent and a second transgene comprising a nucleotide sequence encoding a VEGF-D agent, the genome does not further comprise a transgene comprising a nucleotide sequence encoding a checkpoint inhibitor (e.g., an antibody that specifically binds to PD-1 and blocks binding of PD-1 to PDL1, PDL2 or both, such as pembrolizumab or nivolumab; an antibody that specifically binds to PDL1 and blocks binding of PDL1 to PD1, CD80 or both, such as atezolizumab, durvalumab, or cemiplimab; an antibody that specifically binds to CLTA-4 and block the interaction of CTLA-4 with its ligands B7.1 and B7.2, such as ipilimumab or tremelimumab; and an antibody that specifically binds to TIM3); a cytokine (e.g., IL-2, IL-12, IL-15, IFN alpha/beta, 41-BB, CD40L, Flt3L, CCL3, CCL5, GM-CSF, etc.); an agonist of a co-stimulatory molecule (e.g., an agonist of ICOS, ICOS-L, OX40, OX40L, etc.); or a cancer antigen (e.g., tumor associated antigen). See, e.g., Section 5.7.2 for examples of checkpoint inhibitors and co-stimulatory molecules. In some embodiments, the recombinant oncolytic virus is pexastimogene devacirepvec (Pexa-Vec, formerly named JX-594), ONCOS (adeno Δ24-RGD-GM-CSF insertion), herpes virus OrienX010, ICOVIR-5, Talimogene Laherparepvec (T-VEC, Imlygic®), VV JX-594, Ad Ad5/3-D24-GMCSF, or CG0070. 
     In certain embodiments, a recombinant oncolytic viruses comprises a genome, wherein the genome comprises a transgene comprising a nucleotide sequence encoding a VEGF-C agent, a VEGF-D agent, or both, operably linked to a regulatory sequence (e.g., a promoter, enhancer or both). 
     5.3.1 Recombinant APMV 
     In one aspect, provided herein are recombinant APMVs comprising a genome, wherein the genome comprises a transgene comprising a nucleotide sequence encoding a VEGFR-3-activating agent. In one embodiment, a VEGFR-3-activating agent is a VEGF-C protein or a VEGF-D protein. In another embodiment, a VEGFR-3-activating agent is a nucleic acid sequence comprising a nucleotide sequence encoding a VEGF-C protein or a VEGF-D protein. The VEGF-C protein or VEGF-D protein may be a derivative of a naturally occurring form of VEGF-C or VEGF-D, respectively. See Section 5.2 and 5.3.2 for examples of VEGF-C proteins, VEGF-D proteins, nucleic acid sequences encoding a VEGF-C protein, and nucleic acid sequences encoding a VEGF-D protein, VEGF-C derivatives, and VEGF-D derivatives. 
     In another aspect, presented herein are recombinant APMVs comprising a packaged genome, wherein the packaged genome comprises a transgene comprising a nucleotide sequence encoding a VEGF-C agent, a VEGF-D agent, or both. In another aspect, provided herein are recombinant APMVs comprising a packaged genome, wherein the genome comprises a transgene comprising a nucleotide sequence encoding a VEGF-C agent and a transgene comprising a nucleotide sequence encoding a VEGF-D agent. See, e.g., Section 5.1.1, 5.3.1.1 and Section 6 for examples of APMVs, the genome of which a transgene encoding a VEGF-C agent or a VEGF-D agent may be incorporated. In a particular embodiment, the genome of the APMV, which the transgene comprising a nucleotide sequence encoding a VEGF-C agent or a VEGF-D agent is incorporated, is the genome of an APMV-1 (e.g., an APMV-1 strain described herein), APMV-2 (e.g., an APMV-2 strain described herein), APMV-3 (e.g., an APMV-3 strain described herein), APMV-4 (e.g., an APMV-4 strain described herein), APMV-5, (e.g., an APMV-4 strain described herein), APMV-6 (e.g., an APMV-4 strain described herein), APMV-7 strain (e.g., an APMV-7 strain described herein), APMV-8 strain (e.g., an APMV-8 strain described herein), or APMV-9 (e.g., an APMV-4 strain described herein). In another embodiment, the genome of the APMV in which the transgene comprising a nucleotide sequence encoding a VEGF-C agent or a VEGF-D agent is incorporated is the genome of an APMV-6 (e.g., an APMV-6 strain described herein) or APMV-9 strain (e.g., an APMV-9 strain described herein). In a specific embodiment, provided herein is a recombinant APMV-1 comprising a packaged genome, wherein the packaged genome comprises a transgene comprising a nucleotide sequence encoding a VEGF-C agent or a VEGF-D agent. In a preferred embodiment, provided herein is a recombinant APMV-4 comprising a packaged genome, wherein the packaged genome comprises (consists of) the negative sense RNA transcribed from the cDNA sequence set forth in SEQ ID NO: 88. In a specific embodiment, provided herein is a recombinant APMV-4 comprising a packaged genome, wherein the packaged genome comprises a transgene comprising a nucleotide sequence encoding a VEGF-C agent or a VEGF-D agent. In a preferred embodiment, provided herein is a recombinant APMV-4 comprising a packaged genome, wherein the packaged genome comprises (consists of) the negative sense RNA transcribed from the cDNA sequence set forth in SEQ ID NO: 90. In a specific embodiment, the protein encoded by the transgene is expressed by cells infected with the recombinant APMV. 
     In certain embodiments, the genome of the recombinant APMV does not comprise a heterologous sequence encoding a heterologous protein other than the protein encoded by the transgene comprising a VEGF-C agent or a VEGF-D agent. In certain embodiments, a recombinant APMV described herein comprises a packaged genome, wherein the genome comprises (or consists of) the genes found in APMV and a transgene. In certain embodiments, a recombinant APMV described herein comprises a packaged genome, wherein the genome comprises (or consists of) the transcription units found in APMV (e.g., transcription units for APMV nucleocapsid, protein, phosphoprotein, matrix protein, fusion protein, hemagglutinin-neuraminidase protein, and large polymerase protein) and a transgene (e.g., in Section 5.3.2), but does not include another other transgenes. 
     5.3.1.1 Backbone of the Recombinant APMV 
     Any APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain may serve as the “backbone” that is engineered to encode a transgene described herein, including, but not limited to, naturally-occurring strains, variants or mutants, mutagenized viruses, or genetically engineered viruses, or any combination thereof. See, e.g., section 5.1 and 6 for examples of APMV that may be engineered to encode a transgene described herein. In certain embodiments, the APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain that is engineered to encode a transgene described herein is a lytic strain. In other embodiments, the APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain that is engineered to encode a transgene described herein is a non-lytic strain. In a specific embodiment, a transgene described herein is incorporated into the genome of APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain that is avirulent in an avian(s) by a method(s) described herein or known to one of skill in the art. In certain embodiments, the APMV-APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain that is engineered to encode a transgene described herein is genetically engineered to be attenuated in a manner that attenuates the pathogenicity of the virus in birds. 
     In another specific embodiment, a transgene is incorporated into the genome of an APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain that has an intracerebral pathogenicity index in day-old chicks of the  Gallus gallus  species of less than 0.7. In certain specific embodiments, the APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain that is engineered to encode a transgene described herein is not pathogenic as assessed by intracranial injection of 1-day-old chicks with the virus, and disease development and death as scored for 8 days. In some embodiments, the APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain that is engineered to encode a transgene described herein has an intracranial pathogenicity index of less than 0.7, less than 0.6, less than 0.5, less than 0.4, less than 0.3, less than 0.2 or less than 0.1. In some embodiments, the APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain that is engineered to encode a transgene described herein has an intracranial pathogenicity index between 0.7 to 0.1, 0.6 to 0.1, 0.5 to 0.1 or 0.4 to 0.1. In certain embodiments, the APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain that is engineered to encode a transgene described herein has an intracranial pathogenicity index of zero. See, e.g., one or more of the following references for a description of an assay that may be used to assess the pathogenicity of an APMV in birds: Hines, N. L. and C. L. Miller, Avian paramyxovirus serotype-1: a review of disease distribution, clinical symptoms, and laboratory diagnostics. Vet Med Int, 2012. 2012: p. 708216; Kim S-H, Xiao S, Shive H, Collins P L, Samal S K., 2012: Replication, Neurotropism, and Pathogenicity of Avian Paramyxovirus Serotypes 1-9 in Chickens and Ducks. PLoS ONE. 7(4): e34927; Subbiah, M., Xiao, S., Khattar, S. K., Dias, F. M., Collins, P. L., &amp; Samal, S. K., 2010: Pathogenesis of two strains of Avian Paramyxovirus serotype 2, Yucaipa and Bangor, in chickens and turkeys. Avian Diseases, 54(3), 1050-1057; Kumar S, Militino Dias F, Nayak B, Collins P L, Samal S. K., 2010: Experimental avian paramyxovirus serotype-3 infection in chickens and turkeys. Veterinary Research.; 41(5):72; Ryota Tsunekuni, Hirokazu Hikono, Takehiko Saito, 2014: Evaluation of avian paramyxovirus serotypes 2 to 10 as vaccine vectors in chickens previously immunized against Newcastle disease virus. Veterinary Immunology and Immunopathology; 160(3-4):184-191; and www.oie.int/fileadmin/Home/fr/Health_standards/tahm/2.03.14 NEWCASTLE DIS.pdf, each of which is incorporated herein by reference in its entirety. 
     In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 that decreases tumor growth and increases survival in a B16-F10/VEGF-C+ syngeneic murine melanoma model as compared to tumor growth and survival in a B16-F10/VEGF-C+ syngeneic murine melanoma model administered phosphate buffered saline (PBS). 
     In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-1 strain. In a specific embodiment, the APMV-1 strain is a naturally-occurring strain. In certain embodiments, the APMV-1 is a lytic strain. In other embodiments, the APMV-APMV-1 strain is a non-lytic strain. In certain embodiments, the APMV-1 strain is lentogenic strain. In some embodiments, the APMV-1 strain is a mesogenic strain. In other embodiments, the APMV-1 strain is a velogenic strain. See, e.g., Newcastle Disease, Avian Paramyoxvirus-1 Infection, Goose Paramyoxvirus Infection, Ranikhet disease, the Center for Food Security &amp; Public Health, Iowa State University, Institute for International Cooperation in Animal Biologies, College of Veterinary Medicine, Iowa State University, pp. 1-9 (January 2016) for a discussion regarding lentogenic, mesogenic and velogenic APMV-1 (otherwise referred to as NDV) strains, which is incorporated herein by reference in its entirety. Specific examples of APMV-1 strains include, but are not limited to, the 73-T strain, NDV HUJ strain, Ulster strain (see, e.g., GenBank No. U25837), MTH-68 strain, Italien strain (see, e.g., GenBank No. EU293914), Hickman strain (see, e.g., Genbank No. AF309418), PV701 strain, Hitchner B1 strain (see, e.g., GenBank No. AF309418 or NC 002617), La Sota strain (see, e.g., GenBank Nos. AY845400 and JF950510.1 and GI No. 56799463), YG97 strain (see, e.g., GenBank Nos. AY351959 or AY390310), MET95 strain (see, e.g., GenBank No. AY143159), Roakin strain (see, e.g., GenBank No. AF124443), and F48E9 strain (see, e.g., GenBank Nos. AF163440 and U25837). In a specific embodiment, the APMV-1 strain is the Hitchner B1 strain. In another specific embodiment, the APMV-1 strain is a B1 strain as identified by GenBank No. AF309418 or NC 002617. In another specific embodiment, the APMV-1 strain is the NDV identified by ATCC No. VR2239. In another specific embodiment, the APMV-1 strain is an NDV described in U.S. Pat. No. 10,035,984, which is incorporated herein by reference in its entirety. 
     In a specific embodiments, a transgene described herein is incorporated into the genome of an APMV-1 that is genetically modified. In one embodiment, a transgene described herein is incorporated into the genome of an APMV-1 strain that is engineered to express a mutated F protein with a mutated cleavage site. In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-1 strain that is engineered to express a mutated F protein in which the cleavage site of the F protein is mutated to produce a polybasic amino acid sequence, which allows the protein to be cleaved by intracellular proteases, which makes the virus more effective in entering cells and forming syncytia. In another specific embodiment, a transgene described herein is incorporated into the genome of an APMV-1 strain that is engineered to express a mutated F protein in which the cleavage site of the F protein is replaced with a mutated cleavage site containing one or two extra arginine residues, allowing the mutant cleavage site to be activated by ubiquitously expressed proteases of the furin family. Specific examples of NDVs that express such a mutated F protein include, but are not limited to, rNDV/F2aa and rNDV/F3aa. For a description of mutations introduced into a NDV F protein to produce a mutated F protein with a mutated cleavage site, see, e.g., Park et al. (2006) Engineered viral vaccine constructs with dual specificity: avian influenza and Newcastle disease. PNAS USA 103: 8203-2808, which is incorporated herein by reference in its entirety. 
     In another embodiment, a transgene described herein is incorporated into the genome of an APMV-1 strain that is naturally occurring. In a specific embodiment, an APMV-1 strain that is naturally occurring and has an intracerebral pathogenicity index in day-old chicks of the  Gallus gallus  species of less than 0.7 is used in a method of treating cancer described herein. In a specific embodiment, an APMV-1 that is used in a method of treating cancer described herein is an APMV-1 with a genome that has 80%, 85%, 90%, 95% or higher percent identity to the genome of a LaSota strain (e.g., SEQ ID NO: 83 or 84). 
     In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-1 strain that is engineered to express a mutated F protein with the amino acid mutation L289A (i.e., an L to A mutation at the amino acid position corresponding to L289 of the LaSota F protein). For a description of the L289A mutation, see, e.g., Sergei et al. (2000) A Single Amino Acid Change in the Newcastle Disease Virus Fusion Protein Alters the Requirement for UN Protein in Fusion. Journal of Virology 74(11): 5101-5107, which is incorporated herein by reference in its entirety. In specific embodiments, the L289A mutated F protein possesses one, two or three arginine residues in the cleavage site. In a specific embodiment, a transgene described herein is incorporated into the genome of a LaSota strain, which has been engineered to express a mutated F protein with the amino acid mutation L289A (i.e., an L to A mutation at the amino acid position corresponding to L289 of the LaSota F protein). In a specific embodiment, the genetically modified NDV LaSota strain comprises a packaged genome, wherein the packaged genome comprises the negative sense RNA transcribed from the cDNA sequence set forth in SEQ ID NO: 83 or 84. 
     In some embodiments, a transgene described herein is incorporated into the genome of an APMV-1 strain disclosed in Kim et al., 2017, PLOS ONE 12(3): e0173965 and Kim et al., 2016, J. of General Virology 97: 1297-1303, each of which is incorporated herein by reference in its entirety. 
     In certain embodiments, a transgene described herein is incorporated into the genome of an APMV-1 strain that comprises a nucleotide sequence encoding a mutated F protein with an F protein cleavage site of NDV LaSota strain or glycoprotein B of cytomegalovirus (CMV). In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-1 strain that comprises a nucleotide sequence encoding a mutated F protein with an F protein cleavage having one of the following sequence modifications: S116:  111 H-N-R-T-K-S/F 117  (SEQ ID NO: 91); S116K:  111 H-K-T-K-S/F 117  (SEQ ID NO: 92); S116M:  111 H-N-R-M-K-S/F 117  (SEQ ID NO: 93); S116KM:  111 H-N-K-M-K-S/F-I 118  (SEQ ID NO: 94); or R116:  111 H-N-R-T-K-R/F-I 118  (SEQ ID NO: 95), such as described in International Patent Application No. WO 2015/032755. See, e.g., International Patent Application Publication No. WO 2015/032755 for a description of the types of mutated F protein cleavage sites that may be engineered into an NDV F protein, which is incorporated herein by reference in its entirety. In some embodiments, the mutated F protein is in addition to the backbone NDV F protein. In specific embodiments, the mutated F protein replaces the backbone NDV F protein. 
     In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-4 strain. In a preferred embodiment, a transgene described herein is incorporated into the genome of APMV-4/Duck/Hong Kong/D3/1975 strain. One example of a cDNA sequence of the genome of the APMV-4/Duck/Hong Kong/D3/1975 strain may be found in SEQ ID NO:78. In a specific embodiment, the nucleotide sequence of a transgene described herein is incorporated into the genome of APMV-4/Duck/China/G302/2012 strain, APMV4/mallard/Belgium/15129/07 strain, APMV4/Uriah_aalge/Russia/Tyuleniy_Island/115/2015 strain, APMV4/Egyptian goose/South Africa/N1468/2010 strain, or APMV-4/duck/Delaware/549227/2010 strain. One example of a cDNA sequence of the genome of the APMV-4/Duck/China/G302/2012 strain may be found in SEQ ID NO:81. An example of a cDNA sequence of the genome of the APMV4/mallard/Belgium/15129/07 strain may be found in SEQ ID NO:77. An example of a cDNA sequence of the genome of the APMV4/Uriah_aalge/Russia/Tyuleniy_Island/115/2015 strain may be found in SEQ ID NO:79. An example of a cDNA sequence of the genome of the APMV4/Egyptian goose/South Africa/N1468/2010 strain may be found in SEQ ID NO:80. An example of a cDNA sequence of the genome of the APMV-4/duck/Delaware/549227/2010 strain may be found in SEQ ID NO:82. In another specific embodiment, an APMV-4 comprises the cDNA sequence provided in SEQ ID NO: 86. In another specific embodiment, an APMV-4 comprises a cDNA sequence provided in Table 3 or Section 6, infra. 
     In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-4 that decreases tumor growth and increases survival in a B16-F10/VEGF-C+ syngeneic murine melanoma model as compared to tumor growth and survival in a B16-F10/VEGF-C+ syngeneic murine melanoma model administered phosphate buffered saline (PBS). 
     In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-7 strain. In a particular embodiment, a transgene described herein is incorporated into the genome of is APMV-7/dove/Tennessee/4/75. See, e.g., GenBank No. FJ231524.1 for the complete genomic cDNA of APMV-7/dove/Tennessee/4/75. 
     In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-8 strain. In a particular embodiment, a transgene described herein is incorporated into the genome of APMV-8/Goose/Delaware/1053/76. See, e.g., GenBank No. FJ619036.1 for the complete genomic cDNA sequence of APMV-8/Goose/Delaware/1053/76. 
     In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-9 strain. In a particular embodiment, a transgene described herein is incorporated into the genome of APMV-9 duck/New York/22/1978. See, e.g., GenBank No. NC 025390.1 for the complete genomic cDNA sequence of APMV-9 duck/New York/22/1978. 
     In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-2 strain. In a particular embodiment, a transgene described herein is incorporated into the genome of APMV-2 Chicken/California/Yucaipa/1956. See, e.g., GenBank No. EU338414.1 for the complete genomic cDNA sequence of APMV-2 Chicken/California/Yucaipa/1956. 
     In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-3 strain. In a particular embodiment, a transgene described herein is incorporated into the genome of APMV-3 turkey/Wisconsin/68. See, e.g., GenBank No. EU782025.1 for the complete genomic cDNA sequence of APMV-3 turkey/Wisconsin/68. 
     In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-6 strain. In a particular embodiment, a transgene described herein is incorporated into the genome of APMV-6/duck/Hong Kong/18/199/77. See, e.g., GenBank No. EU622637.2 for the complete genomic cDNA sequence of APMV-6/duck/Hong Kong/18/199/77. 
     One skilled in the art will understand that the APMV genomic RNA sequence is the reverse complement of a cDNA sequence encoding the APMV genome. Thus, any program that generates converts a nucleotide sequence to its reverse complement sequence may be utilized to convert a cDNA sequence encoding an APMV genome into the genomic RNA sequence (see, e.g., www.bioinformatics.org/sms/rev_comp.html, www.fr33.net/seqedit.php, and DNAStar). Accordingly, the nucleotide sequences provided in Tables 2 and 3, infra, may be readily converted to the negative-sense RNA sequence of the APMV genome by one of skill in the art. 
     In specific embodiments, a transgene described herein is incorporated into the genome of an APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain, wherein the genome comprises the transcription units of the APMV-4 strain necessary for infection and replication of the virus in a substrate (e.g., a cell line susceptible to APMV-4 infection), subject (e.g., a human subject), or both. In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-1, APMV-2, APMV-3, APMV-4, APMV-5, APMV-6, APMV-7, APMV-8, or APMV-9 strain, wherein the genome comprises a transcription unit encoding the APMV-4 nucleocapsid (N) protein, a transcription unit encoding the APMV phosphoprotein (P), a transcription unit encoding the APMV matrix (M) protein, a transcription unit encoding the APMV fusion (F) protein, a transcription unit encoding the APMV hemagglutinin-neuraminidase (HN) protein, and a transcription unit encoding the APMV large polymerase (L) protein. The transgene may be incorporated into the APMV genome between two transcription units of an APMV described herein (e.g., between the M and P transcription units or between the HN and L transcription units). In certain embodiments, the genome of the APMV does not encode a heterologous protein other than a transgene described herein. 
     In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-1 strain, wherein the genome comprises the transcription units of the APMV-1 strain necessary for infection and replication of the virus in a substrate (e.g., a cell line susceptible to APMV-1 infection), subject (e.g., a human subject), or both. In a specific embodiment, a transgene is incorporated into the genome of an APMV-1 strain, wherein the genome comprises a transcription unit encoding the APMV-1 nucleocapsid (N) protein, a transcription unit encoding the APMV-4 phosphoprotein (P), a transcription unit encoding the APMV-1 matrix (M) protein, a transcription unit encoding the APMV-1 fusion (F) protein, a transcription unit encoding the APMV-1 hemagglutinin-neuraminidase (HN) protein, and a transcription unit encoding the APMV-1 large polymerase (L) protein. The transgene may be incorporated into the APMV-4 genome between two transcription units of an APMV-1 described herein (e.g., between the M and P transcription units or between the HN and L transcription units). In certain embodiments, the genome of the APMV-1 does not encode a heterologous protein other than a transgene described herein. In a specific embodiment, the APMV-1 strain is an APMV-1 described herein (e.g., in this section, Section 5.1.1 or Section 6), such as a LaSota strain or a LaSota strain comprising a mutated F protein. 
     In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-4 strain, wherein the genome comprises the transcription units of the APMV-4 strain necessary for infection and replication of the virus in a substrate (e.g., a cell line susceptible to APMV-4 infection), subject (e.g., a human subject), or both. In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-4 strain, wherein the genome comprises a transcription unit encoding the APMV-4 nucleocapsid (N) protein, a transcription unit encoding the APMV-4 phosphoprotein (P), a transcription unit encoding the APMV-4 matrix (M) protein, a transcription unit encoding the APMV-4 fusion (F) protein, a transcription unit encoding the APMV-4 hemagglutinin-neuraminidase (HN) protein, and a transcription unit encoding the APMV-4 large polymerase (L) protein. The transgene may be incorporated into the APMV-4 genome between two transcription units of an APMV-4 described herein (e.g., between the M and P transcription units or between the HN and L transcription units). In certain embodiments, the genome of the APMV-4 does not encode a heterologous protein other than a transgene described herein. In a specific embodiment, the APMV-4 strain is the APMV-4/Duck/Hong Kong/D3/1975 strain, APMV-4/Duck/China/G302/2012 strain, APMV4/mallard/Belgium/15129/07 strain, APMV4Uriah-aalge/Russia/Tyuleniy_Island/115/2015 strain, APMV4/Egyptian goose/South Africa/NJ468/2010 strain, or APMV4/duck/Delaware/549227/2010 strain. 
     In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-8 strain, wherein the genome comprises the transcription units of the APMV-8 strain necessary for infection and replication of the virus in a substrate (e.g., a cell line susceptible to APMV-8 infection), subject (e.g., a human subject), or both. In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-8 strain, wherein the genome comprises a transcription unit encoding the APMV-8 nucleocapsid (N) protein, a transcription unit encoding the APMV-8 phosphoprotein (P), a transcription unit encoding the APMV-8 matrix (M) protein, a transcription unit encoding the APMV-8 fusion (F) protein, a transcription unit encoding the APMV-8 hemagglutinin-neuraminidase (HN) protein, and a transcription unit encoding the APMV-8 large polymerase (L) protein. The transgene may be incorporated into the APMV-8 genome between two transcription units of an APMV-8 described herein (e.g., between the M and P transcription units or between the HN and L transcription units). In certain embodiments, the genome of the APMV-8 does not encode a heterologous protein other than a transgene described herein. In a specific embodiment, the APMV-8 strain is the APMV-8/Goose/Delaware/1053/76 strain. 
     In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-9 strain, wherein the genome comprises the transcription units of the APMV-9 strain necessary for infection and replication of the virus in a substrate (e.g., a cell line susceptible to APMV-9 infection), subject (e.g., a human subject), or both. In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-9 strain, wherein the genome comprises a transcription unit encoding the APMV-9 nucleocapsid (N) protein, a transcription unit encoding the APMV-9 phosphoprotein (P), a transcription unit encoding the APMV-9 matrix (M) protein, a transcription unit encoding the APMV-9 fusion (F) protein, a transcription unit encoding the APMV-9 hemagglutinin-neuraminidase (HN) protein, and a transcription unit encoding the APMV-9 large polymerase (L) protein. The transgene may be incorporated into the APMV-9 genome between two transcription units of an APMV-9 described herein (e.g., between the M and P transcription units or between the HN and L transcription units). In certain embodiments, the genome of the APMV-9 does not encode a heterologous protein other than a transgene described herein. In a specific embodiment, the APMV-9 strain is the APMV-9 duck/New York/22/1978 strain. 
     In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-7 strain, wherein the genome comprises the transcription units of the APMV-7 strain necessary for infection and replication of the virus in a substrate (e.g., a cell line susceptible to APMV-7 infection), subject (e.g., a human subject), or both. In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-7 strain, wherein the genome comprises a transcription unit encoding the APMV-7 nucleocapsid (N) protein, a transcription unit encoding the APMV-7 phosphoprotein (P), a transcription unit encoding the APMV-7 matrix (M) protein, a transcription unit encoding the APMV-7 fusion (F) protein, a transcription unit encoding the APMV-7 hemagglutinin-neuraminidase (HN) protein, and a transcription unit encoding the APMV-7 large polymerase (L) protein. The transgene may be incorporated into the APMV-7 genome between two transcription units of an APMV-7 described herein (e.g., between the M and P transcription units or between the HN and L transcription units). In certain embodiments, the genome of the APMV-7 does not encode a heterologous protein other than a transgene described herein. In a specific embodiment, the APMV-7 strain is the APMV-7/dove/Tennessee/4/75 strain. 
     In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-2 strain, wherein the genome comprises the transcription units of the APMV-2 strain necessary for infection and replication of the virus in a substrate (e.g., a cell line susceptible to APMV-2 infection), subject (e.g., a human subject), or both. In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-2 strain, wherein the genome comprises a transcription unit encoding the APMV-2 nucleocapsid (N) protein, a transcription unit encoding the APMV-2 phosphoprotein (P), a transcription unit encoding the APMV-2 matrix (M) protein, a transcription unit encoding the APMV-2 fusion (F) protein, a transcription unit encoding the APMV-2 hemagglutinin-neuraminidase (HN) protein, and a transcription unit encoding the APMV-2 large polymerase (L) protein. The transgene may be incorporated into the APMV-2 genome between two transcription units of an APMV-2 described herein (e.g., between the M and P transcription units or between the HN and L transcription units). In certain embodiments, the genome of the APMV-2 does not encode a heterologous protein other than a transgene described herein. In a specific embodiment, the APMV-2 strain is the APMV-2 Chicken/California/Yucaipa/1956 strain. 
     In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-3 strain, wherein the genome comprises the transcription units of the APMV-3 strain necessary for infection and replication of the virus in a substrate (e.g., a cell line susceptible to APMV-3 infection), subject (e.g., a human subject), or both. In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-3 strain, wherein the genome comprises a transcription unit encoding the APMV-3 nucleocapsid (N) protein, a transcription unit encoding the APMV-3 phosphoprotein (P), a transcription unit encoding the APMV-3 matrix (M) protein, a transcription unit encoding the APMV-3 fusion (F) protein, a transcription unit encoding the APMV-3 hemagglutinin-neuraminidase (HN) protein, and a transcription unit encoding the APMV-3 large polymerase (L) protein. The transgene may be incorporated into the APMV-3 genome between two transcription units of an APMV-3 described herein (e.g., between the M and P transcription units or between the HN and L transcription units). In certain embodiments, the genome of the APMV-3 does not encode a heterologous protein other than a transgene described herein. In a specific embodiment, the APMV-3 strain is the APMV-3 turkey/Wisconsin/68 strain. 
     In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-6 strain, wherein the genome comprises the transcription units of the APMV-6 strain necessary for infection and replication of the virus in a substrate (e.g., a cell line susceptible to APMV-6 infection), subject (e.g., a human subject), or both. In a specific embodiment, a transgene described herein is incorporated into the genome of an APMV-6 strain, wherein the genome comprises a transcription unit encoding the APMV-6 nucleocapsid (N) protein, a transcription unit encoding the APMV-6 phosphoprotein (P), a transcription unit encoding the APMV-6 matrix (M) protein, a transcription unit encoding the APMV-6 fusion (F) protein, a transcription unit encoding the APMV-6 hemagglutinin-neuraminidase (HN) protein, and a transcription unit encoding the APMV-6 large polymerase (L) protein. The transgene may be incorporated into the APMV-6 genome between two transcription units of an APMV-6 described herein (e.g., between the M and P transcription units or between the HN and L transcription units). In certain embodiments, the genome of the APMV-6 does not encode a heterologous protein other than a transgene described herein. In a specific embodiment, the APMV-6 strain is the APMV-6/duck/Hong Kong/18/199/77 strain. 
     In certain embodiments in which a recombinant APMV comprising a packaged genome, wherein the genome comprises a first transgene comprising a nucleotide sequence encoding a VEGF-C agent, a VEGF-D agent, or both, or a first transgene comprising a nucleotide sequence encoding a VEGF-C agent and a second transgene comprising a nucleotide sequence encoding a VEGF-D agent, the genome does not further comprise a transgene comprising a nucleotide sequence encoding a heterologous protein. In some embodiments in which a recombinant APMV comprising a packaged genome, wherein the genome comprises a first transgene comprising a nucleotide sequence encoding a VEGF-C agent, a VEGF-D agent, or both, or a first transgene comprising a nucleotide sequence encoding a VEGF-C agent and a second transgene comprising a nucleotide sequence encoding a VEGF-D agent, the genome does not further comprise a transgene comprising a nucleotide sequence encoding a heterologous antigen (e.g., a bacterial antigen, a viral antigen, a fungal antigen, a protozoal antigen, a helminth antigen or a cancer antigen). In certain embodiments in which a recombinant APMV comprising a packaged genome, wherein the genome comprises a first transgene comprising a nucleotide sequence encoding a VEGF-C agent, a VEGF-D agent, or both, or a first transgene comprising a nucleotide sequence encoding a VEGF-C agent and a second transgene comprising a nucleotide sequence encoding a VEGF-D agent, the genome does not further comprise a transgene comprising a nucleotide sequence encoding a checkpoint inhibitor (e.g., an antibody that specifically binds to PD-1 and blocks binding of PD-1 to PDL1, PDL2 or both, such as pembrolizumab or nivolumab; an antibody that specifically binds to PDL1 and blocks binding of PDL1 to PD1, CD80 or both, such as atezolizumab, durvalumab, or cemiplimab; and an antibody that specifically binds to CLTA-4 and block the interaction of CTLA-4 with its ligands B7.1 and B7.2, such as ipilimumab or tremelimumab and an antibody that specifically binds to TIM3); a cytokine (e.g., IL-2, IL-12, IL-15, IFN alpha/beta, 41-BB, CD40L, Flt3L, CCL3, CCL5, GM-CSF, etc.); an agonist of a co-stimulatory molecule (e.g., an agonist of ICOS, ICOS-L, OX40, OX40L, etc.); a cancer antigen (e.g., tumor associated antigen), or a heterologous antigen (e.g., a bacterial, viral, fungal, protozoal, or helminth antigen). See, e.g., Section 5.7.2 for examples of checkpoint inhibitors and co-stimulatory molecules. 
     In a specific embodiment, a recombinant APMV is one described in Section 6, infra. In certain embodiments, a recombinant APMV has the characteristics of a recombinant APMV as described in Section 6, infra. In some embodiments, a recombinant APMV results in one, two or more effects in a tumor, lymph node, or both when administered to a subject with cancer as described in Section 6, infra. 
     5.3.2 Transgenes 
     In one aspect, provided herein is a transgene comprising a nucleotide sequence encoding a VEGFR-3-activating agent. In one embodiment, a VEGFR-3-activating agent is a VEGF-C protein or a VEGF-D protein. In another embodiment, a VEGFR-3-activating agent is a nucleic acid sequence comprising a nucleotide sequence encoding a VEGF-C protein or a VEGF-D protein. The VEGF-C protein or VEGF-D protein may be derivatives of VEGF-C or VEGF-D, respectively. See Sections 5.2, 5.3.2 and 6 for examples of VEGF-C proteins, VEGF-D proteins, nucleic acid sequences encoding a VEGF-C protein, nucleic acid sequences encoding a VEGF-D protein, VEGF-C derivatives, and VEGF-D derivatives. See Table 3 for exemplary VEGF-C and VEGF-D nucleotide and amino acid sequences. 
     In another aspect, provided herein is a transgene comprising a nucleotide sequence encoding a vascular endothelial growth factor-C (VEGF-C) agent. See Section 5.2, supra, for VEGF-C agents. In a specific embodiment, a transgene comprising a nucleotide sequence encoding a vascular endothelial growth factor-C (VEGF-C) agent is incorporated into the genome of an oncolytic virus described herein (e.g., APMV described herein, such as an APMV-1 or an APMV-4 described herein). The transgene may encode VEGF-C such as set forth in any one of SEQ ID NOs: 19-24, 41-46, 51 or 52. In a specific embodiment, the transgene encodes human VEGF-C such as set forth in any one of SEQ ID NOs: 41-46. See e.g., Section 5.1 and Section 5.3 supra for oncolytic viruses that may be used; with respect to types and strains of APMV that may be used, see Sections 5.1.1 and 5.3.1.1 and with respect to VEGF-C agents that may be used, see, e.g., section 5.2. 
     In another aspect, provided herein is a transgene comprising a nucleotide sequence encoding a vascular endothelial growth factor D (VEGF-D) agent. See Section 5.2, supra, for VEGF-D agents. In another specific embodiment, a transgene comprising a nucleotide sequence encoding a vascular endothelial growth factor-D (VEGF-D) agent is incorporated into the genome of an oncolytic virus described herein (e.g., APMV described herein, such as an APMV-1 or an APMV-4 described herein). The transgene may encode VEGF-D, such as set forth in any one of SEQ ID NO: 99-104 See, e.g., Section 5.1 and Section 5.3, supra, for oncolytic viruses that may be used; with respect to types and strains of APMV that may be used, see Sections 5.1.1 and 5.3.1.1 and with respect to VEGF-D agents that may be used, see, e.g., section 5.2. 
     In specific embodiments, a transgene comprising a nucleotide sequence encoding a VEGF-C agent or a VEGF-D agent comprises appropriate signals in the transgene for recognition by the virus and a valid Kozak sequence(s) (e.g., to improve eukaryotic ribosomal translation). In certain embodiments, a transgene comprising a nucleotide sequence encoding a VEGF-C agent or a VEGF-D agent comprises appropriate signals in the transgene for recognition by the virus, a valid Kozak sequence(s) (e.g., to improve eukaryotic ribosomal translation), and a restriction site to facilitate cloning. In specific embodiments, a transgene comprising a nucleotide sequence encoding a VEGF-C agent or a VEGF-D agent comprises APMV regulatory signals (e.g., gene end, intergenic, and gene start sequences) and Kozak sequences. In some embodiments, a transgene comprising a nucleotide sequence encoding a VEGF-C agent or a VEGF-D agent comprises APMV regulatory signals (e.g., gene end, intergenic, and gene start sequences), Kozak sequences and restriction sites to facilitate cloning. In certain embodiments, a transgene comprising a nucleotide sequence encoding a VEGF-C agent or a VEGF-D agent comprises APMV regulatory signals (e.g., gene end, intergenic and gene start sequences), Kozak sequences, restriction sites to facilitate cloning, and additional nucleotides in the non-coding region to ensure compliance with the rule of six. In a preferred embodiment, the transgene complies with the rule of six. In a specific embodiment, a transgene comprises the nucleotide sequence set forth in SEQ ID NO: 87 or 89. 
     VEGF-C 
     In a specific embodiment, a transgene comprising a nucleotide sequence encoding a VEGF-C agent is incorporated into the genome of an oncolytic virus described herein, such as an APMV (e.g., APMV-1 or APMV-4). See, e.g., Section 5.1. and Section 5.3, supra, for oncolytic viruses that may be used. A nucleotide sequence may encode precursor VEGF-C, pro-VEGF-C-ΔC, or mature VEGF-C. In one embodiment, a nucleotide sequence encodes a full-length form of VEGF-C. In some embodiments, a nucleotide sequence encodes unprocessed form of VEGF-C. In a specific embodiment, a nucleotide sequence encodes human VEGF-C. In another specific embodiment, human VEGF-C comprises the amino acid sequence set forth in any one of SEQ ID NOs: 41-46. In another specific embodiment, the nucleic acid sequence encoding a human VEGF-C comprises the nucleotide sequence set forth in any one of SEQ ID NOs: 29-40. In another specific embodiment, a nucleotide sequence encodes murine VEGF-C. In another specific embodiment, murine VEGF-C comprises the amino acid sequence set forth in SEQ ID NO: 19-24. In another specific embodiment, the nucleic acid sequence encoding a murine VEGF-C comprises the nucleotide sequence set forth in any one of SEQ ID NOs: 1-18. In another specific embodiment, a nucleotide sequence encodes canine VEGF-C. In another specific embodiment, canine VEGF-C comprises the amino acid sequence set forth in SEQ ID NO: 51 or 52. In another specific embodiment, the nucleic acid sequence encoding canine VEGF-C comprises the nucleotide sequence set forth in SEQ ID NO: 49 or 50. In another specific embodiment, a VEGF-C agent comprises the amino acid or nucleic acid sequence of a VEGF-C construct described in Section 6, infra. 
     In a specific embodiment, a transgene comprises a nucleotide sequence that encodes human VEGF-C. In certain embodiments, a nucleotide sequence encodes the amino acid sequence set forth in any one of SEQ ID NOs: 19-24, 41-46, 51, or 52. In some embodiments, the transgene comprises the nucleotide sequence set forth in any one of SEQ ID NOs: 1-18, 29-40, 49, or 50. One of skill in the art would be able to use such sequence information to produce a transgene for incorporation into the genome of an oncolytic virus described herein, such as an APMV (e.g., APMV-1 or APMV-4). For example, a transgene encoding a human VEGF-C comprising the amino acid sequence set forth in GenBank No. NM_005429.5, Uniprot P49767, or Uniprot Q6FH59 may be incorporated into the genome of any APMV type or strain described herein. In a specific embodiment, such a transgene comprises the sequence set forth in any one of SEQ ID NOs: 29-40. In some embodiments, a transgene comprises the nucleotide sequence of canine VEGF-C, such e.g., provided in GenBank™ accession numbers XM_S40047.6 and XM_02543044. However, given the degeneracy of the nucleic acid code, there are a number of different nucleic acid sequences that may encode the same VEGF-C protein. In a specific embodiment, a transgene comprising a nucleotide sequence encoding VEGF-C (e.g., human VEGF-C) is codon optimized. See, e.g., Section 5.3.2.1, infra, for a discussion regarding codon optimization. In some embodiments, the transgene comprising a nucleotide sequence encoding a human VEGF-C protein comprises the amino acid sequence encoded by the nucleic acid sequence comprising the sequence set forth in any one of SEQ ID NOs: 35-40. The transgene encoding VEGF-C (e.g., human VEGF-C) may be incorporated between any two transcription units (e.g., between the APMV P and M transcription units, or between the HN and L transcription units). 
     In certain embodiments, the VEGF-C may be human, dog, cat, horse, pig, or cow VEGF-C. In a specific embodiment, the VEGF-C is human VEGF-C. GenBank™ accession number NM_005429.5, Uniprot P49767, or Uniprot Q6FH59 provides an exemplary human VEGF-C nucleic acid sequence. GenBank™ accession number NM_005429.5, Uniprot P49767, or Uniprot Q6FH59 provides an exemplary human VEGF-C amino acid sequence. In some embodiments, the VEGF-C is canine VEGF-C, such e.g., provided in GenBank™ accession numbers XM_S40047.6 and XM_02543044. In specific embodiments, the VEGF-C proteins are modified by post-translational processing such as signal peptide cleavage, disulfide bond formation, glycosylation (e.g., N-linked glycosylation), protease cleavage and lipid modification (e.g., S-palmitoylation). In some embodiments, VEGF-C includes a signal sequence. In other embodiments, VEGF-C does not include a signal sequence. The signal sequence can be the naturally occurring signal peptide sequence or a variant thereof. In some embodiments, the signal peptide is a VEGF-C signal peptide. In some embodiments, the signal peptide is heterologous to a VEGF-C signal peptide. In some embodiments, the signal peptide is a  Gaussia  luciferase signal peptide (e.g., SEQ ID NO: 28). In certain embodiments, the signal peptide is a IgG light chain signal peptide (e.g., SEQ ID NO: 26). 
     In a specific embodiment, a transgene comprising a nucleotide sequence encoding a VEGF-C derivative is incorporated into the genome of an oncolytic virus described herein, such as an APMV (e.g., APMV-1 or APMV-4). See, e.g., Section 5.1 and Section 5.3.1, supra, for oncolytic viruses that may be used. In a specific embodiment, a transgene comprises a nucleotide sequence that encodes a human VEGF-C derivative. In another embodiment, a transgene comprises a nucleotide sequence that encodes a canine VEGF-C derivative. One of skill in the art would be able to use the sequence information to produce a transgene for incorporation into the genome of an comprising a nucleotide sequence. In a specific embodiment, a VEGF-C derivative has at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 98%, or 99% amino acid sequence identity to a VEGF-C known to those of skill in the art (e.g., any one of SEQ ID NOs: 19-24, 41-46, 51, or 52). In another specific embodiment, a VEGF-C derivative has at least 85%, 90%, 95%, 96%, 98%, or 99% amino acid sequence identity to a VEGF-C known to those of skill in the art (e.g., any one of SEQ ID NOs: 19-24, 41-46, 51, or 52). In another specific embodiment, a VEGF-C derivative has at least 90%, 95%, 96%, 98%, or 99% amino acid sequence identity to a VEGF-C known to those of skill in the art (e.g., any one of SEQ ID NOs: 19-24, 41-46, 51, or 52). In another specific embodiment, a VEGF-C derivative has at least 95%, 96%, 98%, or 99% amino acid sequence identity to a VEGF-C known to those of skill in the art (e.g., any one of SEQ ID NOs: 19-24, 41-46, 51, or 52). In another embodiment, a VEGF-C derivative has at least 85%, 90%, 95%, 96%, 98% or 99% identity to native human VEGF-C (e.g., SEQ ID NO: 41) or a fragment thereof (e.g., a fragment comprising the VEGF homology domain). In another embodiment, a VEGF-C derivative has at least 85%, 90%, 95%, 96%, 98% or 99% identity to native mature VEGF-C (e.g., SEQ ID NO: 44). In another embodiment, a VEGF-C derivative comprises a VEGF homology domain, wherein the VEGF homology domain has at least 85%, 90%, 95%, 96%, 98% or 99% identity to the VEGF homology domain of native VEGF-C. Methods/techniques known in the art may be used to determine sequence identity (see, e.g., “Best Fit” or “Gap” program of the Sequence Analysis Software Package, version 10; Genetics Computer Group, Inc.). In a specific embodiment, a VEGF-C derivative comprises deleted forms of a known VEGF-C (e.g., human VEGF-C), wherein up to about 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid residues are deleted from the known VEGF-C (e.g., human VEGF-C). Also provided herein are VEGF-C derivatives comprising deleted forms of a known VEGF-C, wherein about 1-3, 3-5, 5-7, 7-10, 10-15, or 15-20 amino acid residues are deleted from the known VEGF-C (e.g., human VEGF-C). Further provided herein are VEGF-C derivatives comprising altered forms of a known VEGF-C (e.g., human VEGF-C), wherein up to about 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid residues of the known VEGF-C are substituted (e.g., conservatively substituted) with other amino acids. In a specific embodiment, the known VEGF-C is human VEGF-C, such as, e.g., provided in GenBank™ accession number NM_005429.5, Uniprot P49767, or Uniprot Q6FH59. In some embodiments, a VEGF-C derivative comprises up to about 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 conservatively substituted amino acids. Examples of conservative amino acid substitutions include, e.g., replacement of an amino acid of one class with another amino acid of the same class. In a particular embodiment, a conservative substitution does not alter the structure or function, or both, of a polypeptide. Classes of amino acids may include hydrophobic (Met, Ala, Val, Leu, Ile), neutral hydrophylic (Cys, Ser, Thr), acidic (Asp, Glu), basic (Asn, Gln, His, Lys, Arg), conformation disruptors (Gly, Pro) and aromatic (Trp, Tyr, Phe). 
     In a specific embodiment, a VEGF-C derivative is at least 80%, 85%, 90%, 95%, 98%, or 99% or is 80% to 85%, 80% to 90%, 80% to 95%, 90% to 95%, 85% to 99%, or 95% to 99% identical (e.g., sequence identity) to a native VEGF-C (e.g., human VEGF-C). In a specific embodiment, a VEGF-C derivative is at least 90%, 95%, 98%, or 99% or is 90% to 95%, 90% to 99%, 95% to 98%, or 95% to 99% identical (e.g., sequence identity) to a native VEGF-C (e.g., human VEGF-C). In another specific embodiment, a VEGF-C derivative is a polypeptide encoded by a nucleic acid sequence that is at least 80%, 85%, 90%, 95%, 98%, or 99% or is 80% to 85%, 80% to 90%, 80% to 95%, 90% to 95%, 85% to 99%, or 95% to 99% identical (e.g., sequence identity) to a nucleic acid sequence encoding a native VEGF-C (e.g., human VEGF-C). In another specific embodiment, a VEGF-C is a polypeptide encoded by a nucleic acid sequence that is at least 90%, 95%, 98%, or 99% or is 90% to 95%, 90% to 99%, 95% to 98%, or 95% to 99% identical (e.g., sequence identity) to a nucleic acid sequence encoding a native VEGF-C. In a specific embodiment, the native VEGF-C is human VEGF-C, such as, e.g., provided in GenBank™ accession number NM_005429.5, Uniprot P49767, or Uniprot Q6FH59. In some embodiments, the native VEGF-C is canine VEGF-C, such as, e.g., provided in GenBank™ accession numbers XM_S40047.6 and XM_02543044. In another specific embodiment, a VEGF-C derivative contains 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more, or 2 to 5, 2 to 10, 5 to 10, 5 to 15, 5 to 20, 10 to 15, or 15 to 20 amino acid mutations (i.e., additions, deletions, substitutions or any combination thereof) relative to a native VEGF-C (e.g., human VEGF-C). In another specific embodiment, a VEGF-C derivative is a polypeptide encoded by nucleic acid sequence that can hybridize under high, moderate or typical stringency hybridization conditions to a nucleic acid sequence encoding a native VEGF-C (e.g., human VEGF-C). Hybridization conditions are known to one of skill in the art (see, e.g., U.S. Patent Application No. 2005/0048549 at, e.g., paragraphs 72 and 73). In another specific embodiment, a VEGF-C derivative is a polypeptide encoded by a nucleic acid sequence that can hybridize under high, moderate or typical stringency hybridization conditions to a nucleic acid sequence encoding a fragment of a native VEGF-C (e.g., human VEGF-C) of at least 10 contiguous amino acids, at least 12 contiguous amino acids, at least 15 contiguous amino acids, at least 20 contiguous amino acids, at least 30 contiguous amino acids, at least 40 contiguous amino acids, at least 50 contiguous amino acids, at least 75 contiguous amino acids, at least 100 contiguous amino acids, at least 125 contiguous amino acids, at least 150 contiguous amino acids, or 10 to 20, 20 to 50, 25 to 75, 25 to 100, 25 to 150, 50 to 75, 50 to 100, 75 to 100, 50 to 150, 75 to 150, 100 to 150, or 100 to 200 contiguous amino acids. In another specific embodiment, a VEGF-C derivative is a fragment of a native VEGF-C (e.g., human VEGF-C). In another specific embodiment, a VEGF-C derivative comprises a fragment of human VEGF-C (e.g., a fragment of SEQ ID NO: 41 or 44). In a specific embodiment, a VEGF-C derivative is a fragment of a native VEGF-C (e.g., a human VEGF-C) that comprises the VEGF homology domain. In another specific embodiment, a VEGF-C derivative comprises a fragment of a human VEGF-C (e.g., SEQ ID NO: 41 or 44), wherein the fragment comprises the VEGF homology domain. In a specific embodiment, a fragment of native VEGF-C retains the ability to bind to VEGFR-3, induces phosphorylation of VEGFR-3 and induces downstream signaling events, such as, e.g., phosphorylation of serine/threonine kinases, such as, e.g., AKT, ERK 1/2, or Stat 3. 
     VEGF-C derivatives also include polypeptides that comprise the amino acid sequence of a naturally occurring mature form of VEGF-C and a heterologous amino acid sequence. VEGF-C derivatives also include polypeptides that comprise the amino acid sequence of a naturally occurring mature form of VEGF-C and a heterologous signal peptide amino acid sequence. In addition, VEGF-C derivatives include polypeptides that have been chemically modified by, e.g., glycosylation, acetylation, pegylation, phosphorylation, amidation, derivitization by known protecting/blocking groups, proteolytic cleavage, linkage to a cellular ligand or other protein moiety, etc. Further, VEGF-C derivatives include polypeptides comprising one or more non-classical amino acids. 
     In a specific embodiment, a VEGF-C derivative binds to VEGFR-3 and induces phosphorylation of VEGFR-3 and activates downstream signaling, e.g., phosphorylation of serine/threonine kinases, such as AKT and ERT1/2 and Stat3. In specific embodiments, the VEGF-C derivative retains one, two, or more, or all of the functions of the native VEGF-C (e.g., human VEGF-C) from which it was derived. Examples of functions of VEGF-C include lymphangiogenesis, lymphatic endothelial proliferation, migration, or activation, lymphatic permeability and contractility, angiogenesis, regulation of blood vessel permeability, endothelial cell growth, macrophage recruitment or modulation of function and immunomodulation. Tests for determining whether or not a VEGF-C derivative retains one or more functions of the native VEGF-C (e.g., human VEGF-C) from which it was derived are known to one of skill in the art and examples are provided herein. In a specific embodiment, a VEGF-C derivative binds to VEGFR-3 but not VEGFR-2. In certain embodiments, a VEGF-C derivative comprises the nucleotide sequence of SEQ ID NO: 2, 3, 5, 6, 8, 9, 11, 12, 14, 15, 17, 18, 30, 31, 33, 34, 36, 37, 39, or 40. In certain embodiments, a VEGF-C derivative comprises the nucleotide sequence of SEQ ID NO: 2, 3, 5, 6, 8, 9, 11, 12, 14, 15, 17, or 18. In certain embodiments, a VEGF-C derivative comprises the nucleotide sequence of SEQ ID NO: 30, 31, 33, 34, 36, 37, 39, or 40. In some embodiments, a VEGF-C derivative is mature VEGF-C Cys156Ser (e.g., SEQ ID NO: 45). In certain embodiments, a VEGF-C derivative is mature VEGF-C Cys137Ala (e.g., SEQ ID NO: 46). 
     In specific embodiments, the transgene comprising a nucleotide sequence encoding VEGF-C or a derivative thereof in a genome of a recombinant oncolytic virus described herein (e.g., APMV, such as APMV-1 or APMV-4) is codon optimized. In specific embodiments, a nucleotide sequence encoding VEGF-C or a derivative thereof in a genome of a recombinant oncolytic virus described herein (e.g., APMV, such as APMV-1 or APMV-4) is codon optimized. 
     VEGF-D 
     In a specific embodiment, a transgene comprising a nucleotide sequence encoding a VEGF-D agent is incorporated into the genome of an oncolytic virus described herein, such as an APMV (e.g., APMV-1 or APMV-4). See, e.g., Section 5.1. and Section 5.3, supra, for oncolytic viruses that may be used. A nucleotide sequence may encode precursor VEGF-D, pro-VEGF-D-ΔC, or mature VEGF-D. In one embodiment, a nucleotide sequence encodes a full-length form of VEGF-D. In some embodiments, a nucleotide sequence encodes unprocessed form of VEGF-D. In a specific embodiment, a nucleotide sequence encodes human VEGF-D. In another specific embodiment, human VEGF-D comprises the amino acid sequence set forth in SEQ ID NO:101-104. In another specific embodiment, the nucleic acid sequence encoding a human VEGF-D comprises the nucleotide sequence set forth in SEQ ID NO: 96. In another specific embodiment, a nucleotide sequence encodes canine VEGF-D. In another specific embodiment, canine VEGF-D comprises the amino acid sequence set forth in SEQ ID NO: 99 or 100. In another specific embodiment, the nucleic acid sequence encoding canine VEGF-D comprises the nucleotide sequence set forth in SEQ ID NO: 97 or 98. 
     In a specific embodiment, a transgene comprises a nucleotide sequence that encodes human VEGF-D. In one embodiment, a nucleotide sequence encodes the amino acid sequence set forth in SEQ ID NO: 101-104. In some embodiments, the transgene comprises the nucleotide sequence set forth in SEQ ID NO: 96. One of skill in the art would be able to use such sequence information to produce a transgene for incorporation into the genome of an oncolytic virus described herein, such as an APMV (e.g., APMV-1 or APMV-4). For example, a transgene encoding a human VEGF-D comprising the amino acid sequence set forth in Uniprot O43915 may be incorporated into the genome of any APMV type or strain described herein. In a specific embodiment, such a transgene comprises the sequence set forth in SEQ ID NO: 96. However, given the degeneracy of the nucleic acid code, there are a number of different nucleic acid sequences that may encode the same VEGF-D protein. In a specific embodiment, a transgene comprising a nucleotide sequence encoding VEGF-D (e.g., human VEGF-D) is codon optimized. See, e.g., Section 5.3.2.1, infra, for a discussion regarding codon optimization. In some embodiments, the transgene comprising a nucleotide sequence encoding a human VEGF-D protein comprises the amino acid sequence encoded by the nucleic acid sequence comprising the sequence set forth in SEQ ID NO: 96. The transgene encoding VEGF-D (e.g., human VEGF-D) may be incorporated between any two transcription units (e.g., between the APMV P and M transcription units, or between the HN and L transcription units). 
     In certain embodiments, the VEGF-D may be human, dog, cat, horse, pig, or cow VEGF-D. In a specific embodiment, the VEGF-D is human VEGF-D. Uniprot O43915 provides an exemplary human VEGF-D nucleic acid sequence. Uniprot O43915 provides an exemplary human VEGF-D amino acid sequence. In other embodiments, the native VEGF-D, is a canine VEGF-D, such as e.g, provided in GenBank™ numbers XM_548869.5 or XM_025437083. In specific embodiments, the VEGF-D proteins are modified by post-translational processing such as signal peptide cleavage, disulfide bond formation, glycosylation (e.g., N-linked glycosylation), protease cleavage and lipid modification (e.g., S-palmitoylation). In some embodiments, VEGF-D protein includes a signal sequence. In other embodiments, VEGF-D protein does not include a signal sequence. The signal sequence can be the naturally occurring signal peptide sequence or a variant thereof. In some embodiments, the signal peptide is a VEGF-D signal peptide. In some embodiments, the signal peptide is heterologous to a VEGF-D signal peptide. 
     In a specific embodiment, a transgene comprising a nucleotide sequence encoding a VEGF-D derivative is incorporated into the genome of an oncolytic virus described herein, such as an APMV (e.g., APMV-1 or APMV-4). See, e.g., Section 5.1 and Section 5.3.1, supra, for oncolytic viruses that may be used. In a specific embodiment, a transgene comprises a nucleotide sequence that encodes a human VEGF-D derivative. In another embodiment, a transgene comprises a nucleotide sequence that encodes a canine VEGF-D derivative. One of skill in the art would be able to use the sequence information to produce a transgene for incorporation into the genome of an comprising a nucleotide sequence. In a specific embodiment, a VEGF-D derivative has at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 98%, or 99% amino acid sequence identity to a VEGF-D known to those of skill in the art (e.g., SEQ ID NO: 99-104). In another specific embodiment, a VEGF-D derivative has at least 85%, 90%, 95%, 96%, 98%, or 99% amino acid sequence identity to a VEGF-D known to those of skill in the art (e.g., SEQ ID NO: 99-104). In another specific embodiment, a VEGF-D derivative has at least 90%, 95%, 96%, 98%, or 99% amino acid sequence identity to a VEGF-D known to those of skill in the art (e.g., SEQ ID NO: 99-104). In another specific embodiment, a VEGF-D derivative has at least 95%, 96%, 98%, or 99% amino acid sequence identity to a VEGF-D known to those of skill in the art (e.g., SEQ ID NO: 99-104). In another embodiment, a VEGF-D derivative has at least 85%, 90%, 95%, 96%, 98% or 99% identity to native human VEGF-D (e.g., SEQ ID NO: 104) or a fragment thereof (e.g., a fragment comprising the VEGF homology domain). In another embodiment, a VEGF-D derivative has at least 85%, 90%, 95%, 96%, 98% or 99% identity to native mature VEGF-D (e.g., SEQ ID NO: 101). In another embodiment, a VEGF-D derivative comprises a VEGF homology domain, wherein the VEGF homology domain has at least 85%, 90%, 95%, 96%, 98% or 99% identity to the VEGF homology domain of native VEGF-D. Methods/techniques known in the art may be used to determine sequence identity (see, e.g., “Best Fit” or “Gap” program of the Sequence Analysis Software Package, version 10; Genetics Computer Group, Inc.). In a specific embodiment, a VEGF-D derivative comprises deleted forms of a known VEGF-D (e.g., human VEGF-D), wherein up to about 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid residues are deleted from the known VEGF-D (e.g., human VEGF-D). Also provided herein are VEGF-D derivatives comprising deleted forms of a known VEGF-D, wherein about 1-3, 3-5, 5-7, 7-10, 10-15, or 15-20 amino acid residues are deleted from the known VEGF-D (e.g., human VEGF-D). Further provided herein are VEGF-D derivatives comprising altered forms of a known VEGF-D (e.g., human VEGF-D), wherein up to about 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid residues of the known VEGF-D are substituted (e.g., conservatively substituted) with other amino acids. In a specific embodiment, the known VEGF-D is human VEGF-D, such as, e.g., provided in Uniprot O43915. In other embodiments, the known VEGF-D is a canine VEGF-D, such as e.g, provided in GenBank™ numbers XM_548869.5 or XM_025437083. In some embodiments, a VEGF-D derivative comprises up to about 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 conservatively substituted amino acids. Examples of conservative amino acid substitutions include, e.g., replacement of an amino acid of one class with another amino acid of the same class. In a particular embodiment, a conservative substitution does not alter the structure or function, or both, of a polypeptide. Classes of amino acids may include hydrophobic (Met, Ala, Val, Leu, Ile), neutral hydrophylic (Cys, Ser, Thr), acidic (Asp, Glu), basic (Asn, Gln, His, Lys, Arg), conformation disruptors (Gly, Pro) and aromatic (Trp, Tyr, Phe). 
     In a specific embodiment, a VEGF-D derivative is at least 80%, 85%, 90%, 95%, 98%, or 99% or is 80% to 85%, 80% to 90%, 80% to 95%, 90% to 95%, 85% to 99%, or 95% to 99% identical (e.g., sequence identity) to a native VEGF-D (e.g., human VEGF-D). In a specific embodiment, a VEGF-D derivative is at least 90%, 95%, 98%, or 99% or is 90% to 95%, 90% to 99%, 95% to 98%, or 95% to 99% identical (e.g., sequence identity) to a native VEGF-D (e.g., human VEGF-D). In another specific embodiment, a VEGF-D derivative is a polypeptide encoded by a nucleic acid sequence that is at least 80%, 85%, 90%, 95%, 98%, or 99% or is 80% to 85%, 80% to 90%, 80% to 95%, 90% to 95%, 85% to 99%, or 95% to 99% identical (e.g., sequence identity) to a nucleic acid sequence encoding a native VEGF-D. In another specific embodiment, a VEGF-D is a polypeptide encoded by a nucleic acid sequence that is at least 90%, 95%, 98%, or 99% or is 90% to 95%, 90% to 99%, 95% to 98%, or 95% to 99% identical (e.g., sequence identity) to a nucleic acid sequence encoding a native VEGF-D. In a specific embodiment, the native VEGF-D is human VEGF-D, such as, e.g., provided in Uniprot O43915. In other embodiments, the native VEGF-D is a canine VEGF-D, such as e.g, provided in GenBank™ numbers XM_548869.5 or XM_025437083. In another specific embodiment, a VEGF-D derivative contains 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more, or 2 to 5, 2 to 10, 5 to 10, 5 to 15, 5 to 20, 10 to 15, or 15 to 20 amino acid mutations (i.e., additions, deletions, substitutions or any combination thereof) relative to a native VEGF-D (e.g., human VEGF-D). In another specific embodiment, a VEGF-D derivative is a polypeptide encoded by nucleic acid sequence that can hybridize under high, moderate or typical stringency hybridization conditions to a nucleic acid sequence encoding a native VEGF-D (e.g., human VEGF-D). Hybridization conditions are known to one of skill in the art (see, e.g., U.S. Patent Application No. 2005/0048549 at, e.g., paragraphs 72 and 73). In another specific embodiment, a VEGF-D derivative is a polypeptide encoded by a nucleic acid sequence that can hybridize under high, moderate or typical stringency hybridization conditions to a nucleic acid sequence encoding a fragment of a native VEGF-D (e.g., human VEGF-D) of at least 10 contiguous amino acids, at least 12 contiguous amino acids, at least 15 contiguous amino acids, at least 20 contiguous amino acids, at least 30 contiguous amino acids, at least 40 contiguous amino acids, at least 50 contiguous amino acids, at least 75 contiguous amino acids, at least 100 contiguous amino acids, at least 125 contiguous amino acids, at least 150 contiguous amino acids, or 10 to 20, 20 to 50, 25 to 75, 25 to 100, 25 to 150, 50 to 75, 50 to 100, 75 to 100, 50 to 150, 75 to 150, 100 to 150, or 100 to 200 contiguous amino acids. In another specific embodiment, a VEGF-D derivative comprises a fragment of human VEGF-D (e.g., a fragment of any one of SEQ ID NOs: 101-104). In another specific embodiment, a VEGF-D derivative is a fragment of a native VEGF-D (e.g., human VEGF-D). In a specific embodiment, a VEGF-D derivative is a fragment of a native VEGF-D (e.g., a human VEGF-D) that comprises the VEGF homology domain. In another specific embodiment, a VEGF-D derivative comprises a fragment of a human VEGF-D (e.g., a fragment of SEQ ID NO: 101-104), wherein the fragment comprises the VEGF homology domain. In a specific embodiment, a fragment of native VEGF-D retains the ability to bind to VEGFR-3, induces phosphorylation of VEGFR-3 and induces downstream signaling events, such as, e.g., phosphorylation of serine/threonine kinases, such as, e.g., AKT, ERK 1/2, or Stat 3. 
     VEGF-D derivatives also include polypeptides that comprise the amino acid sequence of a naturally occurring mature form of VEGF-D and a heterologous amino acid sequence. VEGF-D derivatives also include polypeptides that comprise the amino acid sequence of a naturally occurring mature form of VEGF-D and a heterologous signal peptide amino acid sequence. In addition, VEGF-D derivatives include polypeptides that have been chemically modified by, e.g., glycosylation, acetylation, pegylation, phosphorylation, amidation, derivitization by known protecting/blocking groups, proteolytic cleavage, linkage to a cellular ligand or other protein moiety, etc. Further, VEGF-D derivatives include polypeptides comprising one or more non-classical amino acids. 
     In a specific embodiment, a VEGF-D derivative binds to VEGFR-3 and induces phosphorylation of VEGFR-3 and activates downstream signaling, e.g., phosphorylation of serine/threonine kinases, such as AKT and ERT. In specific embodiments, the VEGF-D derivative retains one, two, or more, or all of the functions of the native VEGF-D (e.g., human VEGF-D) from which it was derived. Examples of functions of VEGF-D include lymphatic endothelial proliferation and migration, lymphatic permeability and contractility, angiogenesis, and remodeling of lymphatic and blood vessels. Tests for determining whether or not a VEGF-D derivative retains one or more functions of the native VEGF-D (e.g., human VEGF-D, such as, e.g., SEQ ID NO: 101 or 104) from which it was derived are known to one of skill in the art and examples are provided herein. In a specific embodiment, a VEGF-D derivative binds to VEGFR-3 but not VEGFR-2. 
     In specific embodiments, the transgene comprising a nucleotide sequence encoding VEGF-D or a derivative thereof in a genome of a recombinant oncolytic virus described herein (e.g., APMV, such as APMV-1 or APMV-4) is codon optimized. In specific embodiments, a nucleotide sequence encoding VEGF-D or a derivative thereof in a genome of a recombinant oncolytic virus described herein (e.g., APMV, such as APMV-1 or APMV-4) is codon optimized. 
     5.3.2.1 Codon Optimization 
     Any codon optimization technique known to one of skill in the art may be used to codon optimize a nucleic acid sequence encoding a VEGFR-3-activating agent, VEGF-C agent or a VEGF-D agent. Methods of codon optimization are known in the art, e.g, the OptimumGene™ (GenScript®) protocol and Genewiz® protocol, which are incorporated by reference herein in its entirety. See also U.S. Pat. No. 8,326,547 for methods for codon optimization, which is incorporated herein by reference in its entirety. 
     As an exemplary method for codon optimization, each codon in the open frame of the nucleic acid sequence encoding a VEGF-C agent or a VEGF-D agent is replaced by the codon most frequently used in mammalian proteins. This may be done using a web-based program (www.encorbio.com/protocols/Codon.htm) that uses the Codon Usage Database, maintained by the Department of Plant Gene Research in Kazusa, Japan. This nucleic acid sequence optimized for mammalian expression may be inspected for: (1) the presence of stretches of 5×A or more that may act as transcription terminators; (2) the presence of restriction sites that may interfere with subcloning; and (3) compliance with the rule of six for viruses, such as APMV, that follow the rule of six. Following inspection, (1) stretches of 5×A or more that may act as transcription terminators may be replaced by synonymous mutations; (2) restriction sites that may interfere with subcloning may be replaced by synonymous mutations; (3) a virus&#39;s regulatory signals, such as APMV regulatory signals (gene end, intergenic and gene start sequences), and Kozak sequences for optimal protein expression may be added; and (4) nucleotides may be added in the non-coding region to ensure compliance with the rule of six for viruses, such as APMV, that follow the rule of six. Synonymous mutations are typically nucleotide changes that do not change the amino acid encoded. For example, in the case of a stretch of 6 As (AAAAAA), which sequence encodes Lys-Lys, a synonymous sequence would be AAGAAG, which sequence also encodes Lys-Lys. 
     5.4 Construction of Oncolytic Viruses 
     Techniques known to one of skill in the art may be used to generate/produce an oncolytic virus described herein. See, e.g., Pleschka et al., 1996, J. Virol. 70(6): 4188-4192; Neumann et al., 2005, PNAS 102(46) 16825-16829; Anderson et al., 2000, Gene Therapy 7: 1034-1038; Goins et al., 2008, Methods Mol. Biol. 433: 97-113; Ruedas et al., 2017, Methods Mol. Biol. 1581: 203-222; Hruby, 1990, Clin. Microbiol. Rev. 3(2): 153-170; Mura et al., npj Vaccines 4: 12; Pfaller et al., 2015, Virology 479-480: 331-344; Stanway et al., 1986, J. Virology 57: 1187-1190; Kaptein et al., 1997, Gene Therapy 4: 172-176 for examples of techniques known in the art for the generation/production of an oncolytic virus described herein. 
     Methods for cloning a recombinant oncolytic virus to encode a transgene and express a heterologous protein encoded by the transgene are known to one skilled in the art, such as, e.g., insertion of the transgene into a restriction site that has been engineered into the viral genome, inclusion appropriate signals in the transgene for recognition by the virus, and inclusion of a valid Kozak sequence (e.g., to improve eukaryotic ribosomal translation). 
     5.4.1 Construction of APMVs 
     APMVs and other negative-sense single-stranded RNA viruses (see, e.g., Sections 5.1, 5.3 and 6) can be generated using the reverse genetics technique. The reverse genetics technique involves the preparation of synthetic recombinant viral RNAs that contain the non-coding regions of the negative-strand, viral RNA which are essential for the recognition by viral polymerases and for packaging signals necessary to generate a mature virion. The recombinant RNAs are synthesized from a recombinant DNA template and reconstituted in vitro with purified viral polymerase complex to form recombinant ribonucleoproteins (RNPs) which can be used to transfect cells. A more efficient transfection is achieved if the viral polymerase proteins are present during transcription of the synthetic RNAs either in vitro or in vivo. The synthetic recombinant RNPs can be rescued into infectious virus particles. The foregoing techniques are described in U.S. Pat. No. 5,166,057 issued Nov. 24, 1992; in U.S. Pat. No. 5,854,037 issued Dec. 29, 1998; in U.S. Pat. No. 6,146,642 issued Nov. 14, 2000; in European Patent Publication EP 0702085A1, published Feb. 20, 1996; in U.S. patent application Ser. No. 09/152,845; in International Patent Publications PCT WO97/12032 published Apr. 3, 1997; WO96/34625 published Nov. 7, 1996; in European Patent Publication EP A780475; WO 99/02657 published Jan. 21, 1999; WO 98/53078 published Nov. 26, 1998; WO 98/02530 published Jan. 22, 1998; WO 99/15672 published Apr. 1, 1999; WO 98/13501 published Apr. 2, 1998; WO 97/06270 published Feb. 20, 1997; and EPO 780 475A1 published Jun. 25, 1997, each of which is incorporated by reference herein in its entirety. 
     The helper-free plasmid technology can also be utilized to engineer an APMV and other negative-sense single-stranded RNA viruses. In particular, helper-free plasmid technology can be utilized to engineer a recombinant APMV and other negative-sense single-stranded RNA viruses. Briefly, a complete cDNA of an APMV (e.g., an APMV-4 strain) is constructed, inserted into a plasmid vector and engineered to contain a unique restriction site between two transcription units (e.g., the APMV P and M transcription units; or the APMV HN and L transcription units). A nucleotide sequence encoding a heterologous amino acid sequence (e.g., a transgene or other sequence) may be inserted into the viral genome at the unique restriction site. Alternatively, a nucleotide sequence encoding a heterologous amino acid sequence (e.g., a transgene or other sequence) may be engineered into an APMV transcription unit so long as the insertion does not affect the ability of the virus to infect and replicate. The single segment is positioned between a T7 promoter and the hepatitis delta virus ribozyme to produce an exact negative or positive transcript from the T7 polymerase. The plasmid vector and expression vectors comprising the necessary viral proteins are transfected into cells leading to production of recombinant viral particles (see, e.g., International Publication No. WO 01/04333; U.S. Pat. Nos. 7,442,379, 6,146,642, 6,649,372, 6,544,785 and 7,384,774; Swayne et al. (2003). Avian Dis. 47:1047-1050; and Swayne et al. (2001). J. Virol. 11868-11873, each of which is incorporated by reference in its entirety). See also, e.g., Nolden et al., Scientific Reports 6: 23887 (2016) for reverse genetic techniques to generate negative-strand RNA viruses, which is incorporated herein by reference. 
     Bicistronic techniques to produce multiple proteins from a single mRNA are known to one of skill in the art. Bicistronic techniques allow the engineering of coding sequences of multiple proteins into a single mRNA through the use of IRES sequences. IRES sequences direct the internal recruitment of ribosomes to the RNA molecule and allow downstream translation in a cap independent manner. Briefly, a coding region of one protein is inserted downstream of the ORF of a second protein. The insertion is flanked by an IRES and any untranslated signal sequences necessary for proper expression and/or function. The insertion must not disrupt the open reading frame, polyadenylation or transcriptional promoters of the second protein (see, e.g., Garcia-Sastre et al., 1994, J. Virol. 68:6254-6261 and Garcia-Sastre et al., 1994 Dev. Biol. Stand. 82:237-246, each of which are incorporated by reference herein in their entirety). 
     Methods for cloning a recombinant APMV to encode a transgene and express a heterologous protein encoded by the transgene are known to one skilled in the art, such as, e.g., insertion of the transgene into a restriction site that has been engineered into the APMV genome, inclusion appropriate signals in the transgene for recognition by the APMV RNA-dependent-RNA polymerase (e.g., sequences upstream of the open reading frame of the transgene that allow for the APMV polymerase to recognize the end of the previous gene and the beginning of the transgene, which may be, e.g., spaced by a single nucleotide intergenic sequence), inclusion of a valid Kozak sequence (e.g., to improve eukaryotic ribosomal translation); incorporation of a transgene that satisfies the “rule of six” for APMV cloning; and inclusion of silent mutations to remove extraneous gene end and/or gene start sequences within the transgene. Regarding the Rule of Six, one skilled in the art will understand that efficient replication of APMV (and more generally, most members of the paramyxoviridae family) is dependent on the genome length being a multiple of six, known as the “rule of six” (see, e.g., Calain, P. &amp; Roux, L. The rule of six, a basic feature of efficient replication of Sendai virus defective interfering RNA. J. Virol. 67, 4822-4830 (1993)). Thus, when constructing a recombinant APMV described herein, care should be taken to satisfy the “Rule of Six” for APMV cloning. Methods known to one skilled in the art to satisfy the Rule of Six for APMV cloning may be used, such as, e.g., addition of nucleotides downstream of the transgene. See, e.g., Ayllon et al., Rescue of Recombinant Newcastle Disease Virus from cDNA. J. Vis. Exp. (80), e50830, doi:10.3791/50830 (2013) for a discussion of methods for cloning and rescuing of APMV (e.g., a recombinant APMV), which is incorporated by reference herein in its entirety. 
     5.5 Propagation of Oncolytic Viruses 
     An oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6) can be propagated in any substrate that allows the virus to grow to titers that permit the uses of the viruses described herein. In one embodiment, the substrate allows the oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6). In a specific embodiment, the substrate allows the oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6), to grow to titers comparable to those determined for the corresponding wild-type viruses. 
     An oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6), may be grown in cells (e.g., avian cells, chicken cells, etc.) that are susceptible to infection by the viruses, embryonated eggs (e.g., chicken eggs or quail eggs) or animals (e.g., birds). Such methods are well-known to those skilled in the art. In a specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6), may be propagated in cancer cells, e.g., carcinoma cells (e.g., breast cancer cells and prostate cancer cells), sarcoma cells, leukemia cells, lymphoma cells, and germ cell tumor cells (e.g., testicular cancer cells and ovarian cancer cells). In another specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6), may be propagated in a cell line, e.g., cancer cell lines such as HeLa cells, MCF7 cells, B16-F10 cells, CT26 cells, TC-1 cells, THP-1 cells, U87 cells, DU145 cells, Lncap cells, and T47D cells. In certain embodiments, the cells or cell lines (e.g., cancer cells or cancer cell lines) are obtained and/or derived from a human(s). In another embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6), is propagated in chicken cells or embryonated eggs. Representative chicken cells include, but are not limited to, chicken embryo fibroblasts and chicken embryo kidney cells. In a specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6), is propagated in IFN-deficient cells (e.g., IFN-deficient cell lines). In a specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6), is propagated in Vero cells. In another specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6), is propagated in cancer cells. In another specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6), is propagated in chicken eggs or quail eggs. In certain embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6), is first propagated in embryonated eggs and then propagated in cells (e.g., a cell line). 
     An oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6), may be propagated in embryonated eggs, e.g., from 6 to 14 days old, 6 to 12 days old, 6 to 10 days old, 6 to 9 days old, 6 to 8 days old, 8 days old, 9 days old, 10 days old, 8 to 10 days old, 12 days old, or 10 to 12 days old. Young or immature embryonated eggs can be used to propagate an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6). Immature embryonated eggs encompass eggs which are less than ten day old eggs, e.g., eggs 6 to 9 days old or 6 to 8 days old that are IFN-deficient. Immature embryonated eggs also encompass eggs which artificially mimic immature eggs up to, but less than ten day old, as a result of alterations to the growth conditions, e.g., changes in incubation temperatures; treating with drugs; or any other alteration which results in an egg with a retarded development, such that the IFN system is not fully developed as compared with ten to twelve day old eggs. In a specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6), are propagated in 8 or 9 day old embryonated chicken eggs. In another specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6), are propagated in 10 day old embryonated chicken eggs. An oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6), can be propagated in different locations of the embryonated egg, e.g., the allantoic cavity. For a detailed discussion on the growth and propagation viruses, see, e.g., U.S. Pat. Nos. 6,852,522 and 7,494,808, both of which are hereby incorporated by reference in their entireties. 
     In a specific embodiment, provided herein is a cell (e.g., a cell line) or embryonated egg (e.g., a chicken embryonated egg) comprising an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6). Examples of cells as well as embryonated eggs which may comprise an oncolytic virus described herein, such as an APMV described herein, may be found above. In a specific embodiment, provided herein is a method for propagating an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6), the method comprising culturing a substrate (e.g., a cell line or embryonated egg) infected with the virus. In another specific embodiment, provided herein is a method for propagating an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3 and 6), the method comprising: (a) culturing a substrate (e.g., a cell line or embryonated egg) infected with the virus; and (b) isolating or purifying the virus from the substrate. In certain embodiments, these methods involve infecting the substrate with the oncolytic virus (such as an APMV described herein) prior to culturing the substrate. See, e.g., Section 6, infra, for methods that may be used to propagate an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV described herein). 
     For virus isolation, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6), can be removed from embryonated eggs or cell culture and separated from cellular components, typically by well-known clarification procedures, e.g., such as centrifugation, depth filtration, and microfiltration, and may be further purified as desired using procedures well known to those skilled in the art, e.g., tangential flow filtration (TFF), density gradient centrifugation, differential extraction, or chromatography. 
     In a specific embodiment, provided herein is a method for producing a pharmaceutical composition (e.g., an immunogenic composition) comprising an oncolytic virus described herein, such as APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6), the method comprising (a) propagating an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6), in a cell (e.g., a cell line) or embyronated egg; and (b) isolating the virus from the cell or embyronated egg. The method may further comprise adding the oncolytic virus (e.g., APMV) to a container along with a pharmaceutically acceptable carrier. 
     In a specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6), is propagated, isolated, and/or purified according to a method described in Section 6. In a specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV; see, also, e.g., Sections 5.1, 5.3, and 6), is either propagated, isolated, or purified, or any two or all of the foregoing, using a method described in Section 6. 
     5.6 Compositions and Routes of Administration 
     Encompassed herein is the use of an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV described herein), in compositions. Also encompassed herein is the use of a VEGF-C agent or a VEGF-D agent in compositions. In a specific embodiment, the compositions are pharmaceutical compositions. The compositions may be used in methods of treating cancer. 
     In one embodiment, a pharmaceutical composition comprises an oncolytic virus described herein (e.g., a naturally occurring oncolytic virus or a recombinant oncolytic virus described herein), in an admixture with a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition further comprises one or more additional prophylactic or therapeutic agents, such as described in Section 5.7.2, infra. In a specific embodiment, a pharmaceutical composition comprises an effective amount of an oncolytic virus described herein (e.g., a naturally occurring oncolytic virus or a recombinant oncolytic virus described herein), and optionally one or more additional prophylactic or therapeutic agents, in a pharmaceutically acceptable carrier. In some embodiments, an oncolytic virus described herein (e.g., a naturally occurring oncolytic virus or a recombinant oncolytic virus described herein) is the only active ingredient included in the pharmaceutical composition. In certain embodiments, a pharmaceutical composition comprising an oncolytic virus described herein (e.g., a naturally occurring oncolytic virus or a recombinant oncolytic virus described herein) does not comprise an antigen (e.g., a bacterial antigen, a viral antigen, a fungal antigen, a protozoal antigen, a helminth antigen or a cancer antigen). 
     In another embodiment, a pharmaceutical composition comprises an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV described herein), in an admixture with a pharmaceutically acceptable carrier. In a specific embodiment, the APMV is an APMV-4 described herein. In other embodiments, the APMV is an APMV-6, APMV-7, APMV-8 or APMV-9 described herein. In a specific embodiment, the APMV is a recombinant APMV described herein. In a particular embodiment, the APMV is a recombinant APMV-4 comprising a packaged genome, wherein the packaged genome comprises the negative sense RNA transcribed from the cDNA sequence set forth in SEQ ID NO: 88 or 90. In some embodiments, the pharmaceutical composition further comprises one or more additional prophylactic or therapeutic agents, such as described in Section 5.7.2, infra. In a specific embodiment, a pharmaceutical composition comprises an effective amount of an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV described herein), and optionally one or more additional prophylactic or therapeutic agents, in a pharmaceutically acceptable carrier. In some embodiments, an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV described herein) is the only active ingredient included in the pharmaceutical composition. In certain embodiments, a pharmaceutical composition comprising an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV described herein) does not further comprise an antigen (e.g., a cancer antigen, a bacterial antigen, a fungal antigen, a protozoal antigen, a viral antigen or a helminth antigen). 
     In another embodiment, a pharmaceutical composition (e.g., an oncolysate vaccine) comprises a protein concentrate or a preparation of plasma membrane fragments from oncolytic virus infected cancer cells, in an admixture with a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition further comprises one or more additional prophylactic or therapeutic agents, such as described in Section 5.7.2, infra. In another embodiment, a pharmaceutical composition (e.g., a whole cell vaccine) comprises cancer cells infected with an oncolytic virus, in an admixture with a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition further comprises one or more additional prophylactic or therapeutic agents, such as described in Section 5.7.2, infra. 
     In another embodiment, a pharmaceutical composition (e.g., an oncolysate vaccine) comprises a protein concentrate or a preparation of plasma membrane fragments from APMV infected cancer cells, in an admixture with a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition further comprises one or more additional prophylactic or therapeutic agents, such as described in Section 5.7.2, infra. In another embodiment, a pharmaceutical composition (e.g., a whole cell vaccine) comprises cancer cells infected with APMV, in an admixture with a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition further comprises one or more additional prophylactic or therapeutic agents, such as described in Section 5.7.2, infra. 
     In another embodiment, provided herein is a pharmaceutical composition comprising a VEGFR-3-activating agent in an admixture with a pharmaceutically acceptable carrier. In some embodiments, a VEGFR-3-activating agent described herein is the only active ingredient included in the pharmaceutical composition. In other embodiments, the pharmaceutical composition further comprises an oncolytic virus described herein, such as an APMV described herein. In some embodiments, the pharmaceutical composition further comprises one or more additional prophylactic or therapeutic agents, such as described in Section 5.7.2, infra. In certain embodiments, a pharmaceutical composition comprises a VEGFR-3-activating agent and one or more additional prophylactic or therapeutic agents, such as described in Section 5.7.2, infra. In some embodiments, a pharmaceutical composition comprises a VEGFR-3-activating agent, an oncolytic virus described herein, such as an APMV described herein, and one or more additional prophylactic or therapeutic agents, such as described in Section 5.7.2, infra. In certain embodiments, a pharmaceutical composition comprises a VEGFR-3-activating agent and an antigen (e.g., a cancer antigen, a bacterial antigen, a fungal antigen, a protozoal antigen, a viral antigen or a helminth antigen). In some embodiments, a pharmaceutical composition comprising a VEGFR-3-activating agent does not comprise an antigen (e.g., a cancer antigen, a bacterial antigen, a fungal antigen, a protozoal antigen, a viral antigen or a helminth antigen). 
     In some embodiments, a VEGFR-3-activating agent is encapsulated within, contained within, complexed to or otherwise associated with a liposome, micelle, or a lipid particle or nanoparticle. In some embodiments, a VEGFR-3-activating agent is encapsulated in the aqueous interior of a liposome, interspersed within the lipid bilayer of a liposome, attached to a liposome via a linking molecule that is associated with both the liposome and the polynucleotide, entrapped in a liposome, complexed with a liposome, dispersed in a solution containing a lipid, mixed with a lipid, combined with a lipid, contained as a suspension in a lipid, contained or complexed with a micelle, or otherwise associated with a lipid. In some embodiments, a VEGFR-3-activating agent is encapsulated or associated with a hydrogel. 
     In some embodiments, a VEGFR-3-activating agent is not encapsulated within, contained within, complexed to or otherwise associated with a liposome, micelle, or a lipid particle or nanoparticle. In some embodiments, a VEGFR-3-activating agent is not encapsulated in the aqueous interior of a liposome, interspersed within the lipid bilayer of a liposome, attached to a liposome via a linking molecule that is associated with both the liposome and the polynucleotide, entrapped in a liposome, complexed with a liposome, dispersed in a solution containing a lipid, mixed with a lipid, combined with a lipid, contained as a suspension in a lipid, contained or complexed with a micelle, or otherwise associated with a lipid. In some embodiments, a VEGFR-3-activating agent is not encapsulated or associated with a hydrogel. 
     In another embodiment, provided herein is a pharmaceutical composition comprising a VEGF-C agent in an admixture with a pharmaceutically acceptable carrier. In some embodiments, a VEGF-C agent described herein is the only active ingredient included in the pharmaceutical composition. In other embodiments, the pharmaceutical composition further comprises an oncolytic virus described herein, such as an APMV described herein. In some embodiments, the pharmaceutical composition further comprises one or more additional prophylactic or therapeutic agents, such as described in Section 5.7.2, infra. In certain embodiments, a pharmaceutical composition comprises a VEGF-C agent and one or more additional prophylactic or therapeutic agents, such as described in Section 5.7.2, infra. In some embodiments, a pharmaceutical composition comprises a VEGF-C agent, an oncolytic virus described herein, such as an APMV described herein, and one or more additional prophylactic or therapeutic agents, such as described in Section 5.7.2, infra. In certain embodiments, a pharmaceutical composition comprises a VEGF-C agent and an antigen (e.g., a cancer antigen, a bacterial antigen, a fungal antigen, a protozoal antigen, a viral antigen or a helminth antigen). In some embodiments, a pharmaceutical composition comprising a VEGF-C agent does not comprise an antigen (e.g., a cancer antigen, a bacterial antigen, a fungal antigen, a protozoal antigen, a viral antigen or a helminth antigen). 
     In some embodiments, a VEGF-C agent is encapsulated within, contained within, complexed to or otherwise associated with a liposome, micelle, or a lipid particle or nanoparticle. In some embodiments, a VEGF-C agent is encapsulated in the aqueous interior of a liposome, interspersed within the lipid bilayer of a liposome, attached to a liposome via a linking molecule that is associated with both the liposome and the polynucleotide, entrapped in a liposome, complexed with a liposome, dispersed in a solution containing a lipid, mixed with a lipid, combined with a lipid, contained as a suspension in a lipid, contained or complexed with a micelle, or otherwise associated with a lipid. In some embodiments, a VEGF-C agent is encapsulated or associated with a hydrogel. 
     In some embodiments, a VEGF-C agent is not encapsulated within, contained within, complexed to or otherwise associated with a liposome, micelle, or a lipid particle or nanoparticle. In some embodiments, a VEGF-C agent is not encapsulated in the aqueous interior of a liposome, interspersed within the lipid bilayer of a liposome, attached to a liposome via a linking molecule that is associated with both the liposome and the polynucleotide, entrapped in a liposome, complexed with a liposome, dispersed in a solution containing a lipid, mixed with a lipid, combined with a lipid, contained as a suspension in a lipid, contained or complexed with a micelle, or otherwise associated with a lipid. In some embodiments, a VEGF-C agent is not encapsulated or associated with a hydrogel. 
     In another embodiment, provided herein is a pharmaceutical composition comprising a VEGF-D agent in an admixture with a pharmaceutically acceptable carrier. In some embodiments, a VEGF-D agent described herein is the only active ingredient included in the pharmaceutical composition. In other embodiments, the pharmaceutical composition further comprises an oncolytic virus described herein, such as an APMV described herein. In certain embodiments, a pharmaceutical composition comprises a VEGF-D agent and one or more additional prophylactic or therapeutic agents, such as described in Section 5.7.2, infra. In some embodiments, a pharmaceutical composition comprises a VEGF-D agent, an oncolytic virus described herein, such as an APMV described herein, and one or more additional prophylactic or therapeutic agents, such as described in Section 5.7.2, infra. In certain embodiments, a pharmaceutical composition comprises a VEGF-D agent and an antigen (e.g., a cancer antigen, a bacterial antigen, a fungal antigen, a protozoal antigen, a viral antigen or a helminth antigen). In some embodiments, a pharmaceutical composition comprising a VEGF-D agent does not comprise an antigen (e.g., a cancer antigen, a bacterial antigen, a fungal antigen, a protozoal antigen, a viral antigen or a helminth antigen). 
     In some embodiments, a VEGF-D agent is encapsulated within, contained within, complexed to or otherwise associated with a liposome, micelle, or a lipid particle or composition, or nanoparticle. In some embodiments, a VEGF-D agent is encapsulated in the aqueous interior of a liposome, interspersed within the lipid bilayer of a liposome, attached to a liposome via a linking molecule that is associated with both the liposome and the polynucleotide, entrapped in a liposome, complexed with a liposome, dispersed in a solution containing a lipid, mixed with a lipid, combined with a lipid, contained as a suspension in a lipid, contained or complexed with a micelle, or otherwise associated with a lipid. In some embodiments, a VEGF-D agent is encapsulated or associated with a hydrogel. 
     In some embodiments, a VEGF-D agent is not encapsulated within, contained within, complexed to or otherwise associated with a liposome, micelle, or a lipid particle or composition, or nanoparticle. In some embodiments, a VEGF-D agent is not encapsulated in the aqueous interior of a liposome, interspersed within the lipid bilayer of a liposome, attached to a liposome via a linking molecule that is associated with both the liposome and the polynucleotide, entrapped in a liposome, complexed with a liposome, dispersed in a solution containing a lipid, mixed with a lipid, combined with a lipid, contained as a suspension in a lipid, contained or complexed with a micelle, or otherwise associated with a lipid. In some embodiments, a VEGF-C agent is not encapsulated or associated with a hydrogel. 
     In another embodiment, provided herein is a pharmaceutical composition comprising a VEGF-C agent and a VEGF-D agent in an admixture with a pharmaceutically acceptable carrier. In some embodiments, a VEGF-C agent described herein and a VEGF-D agent are the only active ingredient included in the pharmaceutical composition. In other embodiments, the pharmaceutical composition further comprises an oncolytic virus described herein, such as an APMV described herein. In some embodiments, the pharmaceutical composition further comprises one or more additional prophylactic or therapeutic agents, such as described in Section 5.7.2, infra. In certain embodiments, a pharmaceutical composition comprises a VEGF-C agent, a VEGF-D agent and one or more additional prophylactic or therapeutic agents, such as described in Section 5.7.2, infra. In some embodiments, a pharmaceutical composition comprises a VEGF-C agent, a VEGF-D agent, an oncolytic virus described herein, such as an APMV described herein, and one or more additional prophylactic or therapeutic agents, such as described in Section 5.7.2, infra. In certain embodiments, a pharmaceutical composition comprising a VEGF-C agent and a VEGF-D agent further comprises an antigen (e.g., a cancer antigen, a bacterial antigen, a fungal antigen, a protozoal antigen, a viral antigen or a helminth antigen). In some embodiments, a pharmaceutical composition comprising a VEGF-C agent and a VEGF-D agent does not comprise an antigen (e.g., a cancer antigen, a bacterial antigen, a fungal antigen, a protozoal antigen, a viral antigen or a helminth antigen). 
     In some embodiments, a VEGF-C agent and a VEGF-D are encapsulated within, contained within, complexed to or otherwise associated with a liposome, micelle, or a lipid particle or composition, or nanoparticle. In some embodiments, a VEGF-C agent and a VEGF-D agent are encapsulated in the aqueous interior of a liposome, interspersed within the lipid bilayer of a liposome, attached to a liposome via a linking molecule that is associated with both the liposome and the polynucleotide, entrapped in a liposome, complexed with a liposome, dispersed in a solution containing a lipid, mixed with a lipid, combined with a lipid, contained as a suspension in a lipid, contained or complexed with a micelle, or otherwise associated with a lipid. In some embodiments, a VEGF-C agent and a VEGF-D agent are encapsulated or associated with a hydrogel. 
     In some embodiments, a VEGF-C agent and a VEGF-D are not encapsulated within, contained within, complexed to or otherwise associated with a liposome, micelle, or a lipid particle or composition, or nanoparticle. In some embodiments, a VEGF-C agent and a VEGF-D agent are not encapsulated in the aqueous interior of a liposome, interspersed within the lipid bilayer of a liposome, attached to a liposome via a linking molecule that is associated with both the liposome and the polynucleotide, entrapped in a liposome, complexed with a liposome, dispersed in a solution containing a lipid, mixed with a lipid, combined with a lipid, contained as a suspension in a lipid, contained or complexed with a micelle, or otherwise associated with a lipid. In some embodiments, a VEGF-C agent and a VEGF-D agent are not encapsulated or associated with a hydrogel. 
     In another embodiment, any one or more of the additional therapies disclosed in Section 5.7.2 may also be provided as a pharmaceutical composition. For example, a pharmaceutical composition may contain polyI:C in an admixture with a pharmaceutically acceptable carrier. 
     The pharmaceutical compositions provided herein can be in any form that allows for the composition to be administered to a subject in need thereof. In a specific embodiment, the pharmaceutical compositions are suitable for veterinary administration, human administration or both. As used herein, the term “pharmaceutically acceptable” means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeias for use in animals, and more particularly in humans. The term “carrier” refers to a diluent, adjuvant, excipient, or vehicle with which the pharmaceutical composition is administered. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid carriers, particularly for injectable solutions. Suitable excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. Examples of suitable pharmaceutical carriers are described in “Remington&#39;s Pharmaceutical Sciences” by E. W. Martin. The formulation should suit the mode of administration. 
     In some embodiments, a pharmaceutical composition described herein comprises an adjuvant. In other embodiments, a pharmaceutical composition described herein does not comprise an adjuvant. An adjuvant may be poly IC or poly ICLC, TLR3 ligand, or a cytokine. 
     In a specific embodiment, the pharmaceutical compositions are formulated to be suitable for the intended route of administration to a subject. The pharmaceutical composition may be formulated for systemic or local administration to a subject. For example, the pharmaceutical composition may be formulated to be suitable for parenteral, intravenous, intraarterial, intrapleural, inhalation, intraperitoneal, oral, intradermal, colorectal, intraperitoneal, intracranial, and intratumoral administration. In a specific embodiment, the pharmaceutical composition may be formulated for intravenous, intraarterial, oral, intraperitoneal, intranasal, intradermal, intratracheal, intrapleural, intracranial, subcutaneous, intramuscular, topical, pulmonary, or intratumoral administration. 
     In a specific embodiment, a pharmaceutical composition comprising an oncolytic virus described herein (e.g., a naturally occurring oncolytic virus or a recombinant oncolytic virus described herein) is formulated to be suitable for intratumoral administration to the subject (e.g., human subject). In a specific embodiment, a pharmaceutical composition comprising an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV described herein) is formulated to be suitable for intratumoral administration to the subject (e.g., human subject). In a specific embodiment, a pharmaceutical composition comprising an APMV-1 described herein is formulated for intratumoral administration to a subject (e.g., a human subject). In a specific embodiment, a pharmaceutical composition comprising an APMV-4 described herein is formulated for intratumoral administration to a subject (e.g., a human subject). In other specific embodiments, a pharmaceutical composition comprising an APMV-2, APMV-3, APMV-5, APMV-6, APMV-7, APMV-8 or APMV-9 described herein is formulated for intratumoral administration to a subject (e.g., a human subject). In another specific embodiment, a pharmaceutical composition comprising a recombinant APMV described herein is formulated for intratumoral administration to the subject (e.g., human subject). 
     In a specific embodiment, a pharmaceutical composition comprising an oncolytic virus described herein (e.g., a naturally occurring oncolytic virus or a recombinant oncolytic virus described herein) is formulated to be suitable for intravenous administration to the subject (e.g., human subject). In a specific embodiment, a pharmaceutical composition comprising an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV described herein) is formulated to be suitable for intravenous administration to the subject (e.g., human subject). In a specific embodiment, a pharmaceutical composition comprising an APMV-1 described herein is formulated for intravenous administration to a subject (e.g., a human subject). In a specific embodiment, a pharmaceutical composition comprising an APMV-4 described herein is formulated for intravenous administration to a subject (e.g., a human subject). In other specific embodiments, a pharmaceutical composition comprising an APMV-2, APMV-3, APMV-5, APMV-6, APMV-7, APMV-8 or APMV-9 described herein is formulated for intravenous administration to a subject (e.g., a human subject). In another specific embodiment, a pharmaceutical composition comprising a recombinant APMV described herein is formulated for intravenous administration to the subject (e.g., human subject). 
     To the extent an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or recombinant APMV described herein), is administered in combination with another therapy, the other therapy (e.g., a VEGF-C agent, VEGF-D agent or a prophylactic or therapeutic agent such as described in Section 5.7.2, infra) may be administered in a separate pharmaceutical composition. In other words, two separate pharmaceutical compositions may be administered to a subject to treat cancer—one pharmaceutical composition comprising an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or recombinant APMV described herein), in an admixture with a pharmaceutically acceptable carrier, and a second pharmaceutical composition comprising another therapy (such as, e.g., a VEGF-C agent, VEGF-D agent, or a prophylactic or therapeutic such as described in Section 5.7.2, infra) in an admixture with a pharmaceutically acceptable carrier. The two pharmaceutical composition may be formulated for the same route of administration to the subject (e.g., human subject) or different routes of administration to the subject (e.g., human subject). For example, the pharmaceutical composition comprising an oncolytic virus described herein, such as an APMV described herein, may be formulated for local administration to a tumor of a subject (e.g. a human subject), while the pharmaceutical composition comprising another therapy (such as, e.g., a VEGF-C agent, VEGF-D agent, or a prophylactic or therapeutic such as described in Section 5.5.2, infra) is formulated for systemic administration to the subject (e.g., human subject). In one specific example, the pharmaceutical composition comprising an oncolytic virus described herein, such as an APMV described herein, may be formulated for intratumoral administration to the subject (e.g., human subject), while the pharmaceutical composition comprising another therapy (such as, e.g., a VEGF-C agent, VEGF-D agent, or a prophylactic or therapeutic such as described in Section 5.7.2, infra) is formulated for intravenous administration, subcutaneous administration or another route of administration to the subject (e.g., human subject). In another example, the pharmaceutical composition comprising an oncolytic virus described herein, such as an APMV described herein, and the pharmaceutical composition comprising another therapy (such as, e.g., a VEGF-C agent, VEGF-D agent, or a prophylactic or therapeutic such as described in Section 5.7.2, infra) may both be formulated for intravenous administration to the subject (e.g., human subject). In another example, the pharmaceutical composition comprising an oncolytic virus described herein, such as an APMV described herein, and the pharmaceutical composition comprising another therapy (such as, e.g., a VEGF-C agent, VEGF-D agent, or a prophylactic or therapeutic such as described in Section 5.7.2, infra) may both be formulated for intratumoral administration to the subject (e.g., human subject). In certain embodiments, a pharmaceutical composition comprising a therapy (such as, e.g., a VEGF-C agent, VEGF-D agent, or a prophylactic or therapeutic such as described in Section 5.7.2, infra), which is used in combination with an oncolytic virus described herein, such as an APMV described herein, or a composition thereof, is formulated for administration by an approved route, such as described in the Physicians&#39; Desk Reference 71 st  ed (2017). 
     5.7 Uses of Oncolytic Virus 
     In one aspect, a virus described herein, such as an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) or a composition thereof, an oncolysate described herein or a composition thereof, or whole cell vaccine may be used in the treatment of cancer. In one embodiment, provided herein are methods for treating cancer, comprising administering to a subject in need thereof a recombinant virus described herein, such as a recombinant oncolytic virus described herein (e.g., a recombinant APMV described herein), or a composition thereof. In another embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of an oncolytic virus described herein, such as a recombinant APMV described herein, or a composition thereof. See Section 5.7.4 for the types of cancer that may be treated in accordance with the methods described herein, Section 5.7.3 for the types of patients that may be treated in accordance with the methods described herein, and Section 5.7.1 for exemplary dosages and regimens for treating cancer in accordance with the methods described herein. In a specific embodiment, provided herein are methods for treating cancer, comprising administering to a subject in need thereof a composition as described in Section 5.6 that comprises a oncolytic virus described herein, such as an APMV described herein. 
     In certain embodiments, provided herein is a method for treating cancer, comprising administering to a subject in need thereof a recombinant oncolytic virus described herein, such as recombinant APMV described herein, or a composition thereof and one or more additional therapies, such as described in Section 5.7.2, infra. In a specific embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of a recombinant oncolytic virus described herein, such as a recombinant APMV described herein, or a composition thereof and an effective amount of one or more additional therapies, such as described in Section 5.7.2, infra. In a particular embodiment, one or more therapies are administered to a subject in combination with a recombinant oncolytic virus described herein, such as a recombinant APMV described herein, or a composition thereof to treat cancer. In a specific embodiment, the additional therapies are currently being used, have been used or are known to be useful in treating cancer. In another embodiment, a recombinant oncolytic virus described herein, such as a recombinant APMV described herein (e.g., a recombinant APMV described in Section 5.1, 5.3 or 6) or a composition thereof is administered to a subject in combination with a supportive therapy, a pain relief therapy, or other therapy that does not have a therapeutic effect on cancer. In certain embodiments, a recombinant oncolytic virus described herein, such as a recombinant APMV described herein, and one or more additional therapies are administered in the same composition. In other embodiments, a recombinant oncolytic virus described herein, such as a recombinant APMV described herein, and one or more additional therapies are administered in different compositions. A recombinant oncolytic virus described herein, such a recombinant APMV described herein, or a composition thereof in combination with one or more additional therapies, such as described herein in Section 5.7.2, infra, may be used as any line of therapy (e.g., a first, second, third, fourth or fifth line therapy) for treating cancer in accordance with a method described herein. See Section 5.7.4 for the types of cancer that may be treated in accordance with the methods described herein, Section 5.7.3 for the types of patients that may be treated in accordance with the methods described herein, and Section 5.7.1 for exemplary dosages and regimens for treating cancer in accordance with the methods described herein. 
     In another aspect, provided herein are methods for treating cancer, comprising administering to a subject in need thereof a virus described herein (e.g., an oncolytic virus described herein) and a VEGFR-3 activating agent. The VEGFR-3 activating agent and virus may be in the same composition or different compositions, and such compositions may or may not include additional therapies, such as described in Section 5.7.2. In certain embodiments, the VEGFR-3 activating agent and oncolytic virus (e.g., APMV) are in the same composition. In other embodiments, the VEGFR-3 activating agent and oncolytic virus (e.g., APMV) are in different compositions. In another embodiment, provided herein are methods for treating cancer, comprising administering to a subject in need thereof a first composition comprising an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and a second composition comprising a VEGFR-3 activating agent. In a specific embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and an effective amount of a VEGFR-3 activating agent. In a specific embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of a first composition comprising an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and an effective amount of a second composition comprising a VEGFR-3 activating agent. See Section 5.7.4 for the types of cancer that may be treated in accordance with the methods described herein, Section 5.7.3 for the types of patients that may be treated in accordance with the methods described herein, and Section 5.7.1 for exemplary dosages and regimens for treating cancer in accordance with the methods described herein. 
     In some embodiments, provided herein are methods for treating cancer, comprising administering to a subject in need thereof an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and a VEGFR-3 activating agent, wherein the method does not involve administering to the subject an antigen (e.g., a bacterial antigen, a viral antigen, a fungal antigen, a protozoal antigen, a helminth antigen or a cancer antigen) or a composition thereof. For example, the oncolytic virus and VEGFR-3 activating agent are not administered to a subject in conjunction with an antigen (e.g., a bacterial antigen, a viral antigen, a fungal antigen, a protozoal antigen, a helminth antigen or a cancer antigen) or a composition thereof. In certain embodiments, the VEGFR-3 activating agent and oncolytic virus (e.g., APMV) are in the same composition. In other embodiments, the VEGFR-3 activating agent and oncolytic virus (e.g., APMV) are in different compositions. In some embodiments, the method further comprises administering VEGF-C or a composition thereof. In another embodiment, provided herein are methods for treating cancer, comprising administering to a subject in need thereof a first composition comprising an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and a second composition comprising a VEGFR-3 activating agent, wherein the method does involve to the subject administering an antigen (e.g., a bacterial antigen, a viral antigen, a fungal antigen, a protozoal antigen, a helminth antigen or a cancer antigen) or a composition thereof. In a specific embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and an effective amount of a VEGFR-3 activating agent, wherein the method does involve administering to the subject an antigen (e.g., a bacterial antigen, a viral antigen, a fungal antigen, a protozoal antigen, a helminth antigen or a cancer antigen) or a composition thereof. In a specific embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of a first composition comprising an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and an effective amount of a second composition comprising a VEGFR-3 activating agent, wherein the method does involve administering to the subject an antigen (e.g., a bacterial antigen, a viral antigen, a fungal antigen, a protozoal antigen, a helminth antigen or a cancer antigen) or a composition thereof. See Section 5.7.4 for the types of cancer that may be treated in accordance with the methods described herein, Section 5.7.3 for the types of patients that may be treated in accordance with the methods described herein, and Section 5.7.1 for exemplary dosages and regimens for treating cancer in accordance with the methods described herein. 
     In certain embodiments, provided herein are methods for treating cancer, comprising administering to a subject in need thereof an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and a VEGFR-3 activating agent, wherein the method does not involve administering to the subject an additional active therapy (e.g., an additional active agent) to treat cancer. In certain embodiments, the VEGFR-3 activating agent and oncolytic virus (e.g., APMV) are in the same composition. In other embodiments, the VEGFR-3 activating agent and oncolytic virus (e.g., APMV) are in different compositions. In another embodiment, provided herein are methods for treating cancer, comprising administering to a subject in need thereof a first composition comprising an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and a second composition comprising a VEGFR-3 activating agent, wherein the method does involve administering to the subject an additional active therapy (e.g., an additional active agent) to treat cancer. In a specific embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and an effective amount of a VEGFR-3 activating agent, wherein the method does involve administering to the subject an additional active therapy (e.g., an additional active agent) to treat cancer. In a specific embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of a first composition comprising an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and an effective amount of a second composition comprising a VEGFR-3 activating agent, wherein the method does involve administering to the subject an additional active therapy (e.g., an additional active agent) to treat cancer. See Section 5.7.4 for the types of cancer that may be treated in accordance with the methods described herein, Section 5.7.3 for the types of patients that may be treated in accordance with the methods described herein, and Section 5.7.1 for exemplary dosages and regimens for treating cancer in accordance with the methods described herein. 
     In some embodiments, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof, a VEGFR-3 activating agent or a composition thereof, and one or more additional therapies, such as described in Section 5.7.2, infra. In a specific embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof, an effective amount of a VEGFR-3 activating agent or a composition thereof, and an effective amount of one or more additional therapies, such as described in Section 5.7.2, infra. In a particular embodiment, one or more therapies are administered to a subject in combination with an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof and a VEGFR-3 activating agent or a composition thereof to treat cancer. In a specific embodiment, the additional therapies are currently being used, have been used or are known to be useful in treating cancer. In another embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein) or a composition thereof and a VEGFR-3 activating agent or a composition thereof are administered to a subject in combination with a supportive therapy, a pain relief therapy, or other therapy that does not have a therapeutic effect on cancer. In certain embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), a VEGFR-3 activating agent and one or more additional therapies are administered in the same composition. In some embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein) is administered in a different composition from a VEGFR-3 activating agent and one or more additional therapies. In certain embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein) and one or more additional therapies are administered in the same composition. In some embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein) and one or more additional therapies are administered in different compositions. In certain embodiments, a VEGFR-3 activating agent and one or more additional therapies are administered in the same composition. In some embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), and a VEGFR-3 activating agent and one or more additional therapies are each administered in different compositions. An oncolytic virus, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof in combination with a VEGFR-3 activating agent and one or more additional therapies, such as described herein in Section 5.7.2, infra, may be used as any line of therapy (e.g., a first, second, third, fourth or fifth line therapy) for treating cancer in accordance with a method described herein. See Section 5.7.4 for the types of cancer that may be treated in accordance with the methods described herein, Section 5.7.3 for the types of patients that may be treated in accordance with the methods described herein, and Section 5.7.1 for exemplary dosages and regimens for treating cancer in accordance with the methods described herein. 
     In another aspect, provided herein are methods for treating cancer, comprising administering to a subject in need thereof a virus described herein (e.g., an oncolytic virus described herein) and a VEGF-C agent. The VEGF-C agent and virus may be in the same composition or different compositions, and such compositions may or may not include additional therapies, such as described in Section 5.7.2. In one embodiment, provided herein are methods for treating cancer, comprising administering to a subject in need thereof an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and a VEGF-C agent. In certain embodiments, the VEGF-C agent and oncolytic virus (e.g., APMV) are in the same composition. In other embodiments, the VEGF-C agent and oncolytic virus (e.g., APMV) are in different compositions. In some embodiments, the method further comprises administering a VEGF-D agent or a composition thereof. In another embodiment, provided herein are methods for treating cancer, comprising administering to a subject in need thereof a first composition comprising an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and a second composition comprising a VEGF-C agent. In a specific embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and an effective amount of a VEGF-C agent. In a specific embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of a first composition comprising an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and an effective amount of a second composition comprising a VEGF-C agent. See Section 5.7.4 for the types of cancer that may be treated in accordance with the methods described herein, Section 5.7.3 for the types of patients that may be treated in accordance with the methods described herein, and Section 5.7.1 for exemplary dosages and regimens for treating cancer in accordance with the methods described herein. 
     In some embodiments, provided herein are methods for treating cancer, comprising administering to a subject in need thereof an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and a VEGF-C agent, wherein the method does not involve administering to the subject an antigen (e.g., a bacterial antigen, a viral antigen, a fungal antigen, a protozoal antigen, a helminth antigen or a cancer antigen) or a composition comprising antigen. For example, the oncolytic virus and VEGF-C agent are not administered to a subject in conjunction with an antigen (e.g., a bacterial antigen, a viral antigen, a fungal antigen, a protozoal antigen, a helminth antigen or a cancer antigen) or a composition thereof. In certain embodiments, the VEGF-C agent and oncolytic virus (e.g., APMV) are in the same composition. In other embodiments, the VEGF-C agent and oncolytic virus (e.g., APMV) are in different compositions. In some embodiments, the method further comprises administering a VEGF-D agent or a composition thereof. In another embodiment, provided herein are methods for treating cancer, comprising administering to a subject in need thereof a first composition comprising an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and a second composition comprising a VEGF-C agent, wherein the method does involve administering to the subject an antigen (e.g., a bacterial antigen, a viral antigen, a fungal antigen, a protozoal antigen, a helminth antigen or a cancer antigen). In a specific embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and an effective amount of a VEGF-C agent, wherein the method does involve administering to the subject an antigen (e.g., a bacterial antigen, a viral antigen, a fungal antigen, a protozoal antigen, a helminth antigen or a cancer antigen). In a specific embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of a first composition comprising an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and an effective amount of a second composition comprising a VEGF-C agent, wherein the method does involve administering to the subject an antigen (e.g., a bacterial antigen, a viral antigen, a fungal antigen, a protozoal antigen, a helminth antigen or a cancer antigen). See Section 5.7.4 for the types of cancer that may be treated in accordance with the methods described herein, Section 5.7.3 for the types of patients that may be treated in accordance with the methods described herein, and Section 5.7.1 for exemplary dosages and regimens for treating cancer in accordance with the methods described herein. 
     In certain embodiments, provided herein are methods for treating cancer, comprising administering to a subject in need thereof an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and a VEGF-C agent, wherein the method does not involve administering to the subject an additional active therapy (e.g., an additional active agent) to treat cancer. In certain embodiments, the VEGF-C agent and oncolytic virus (e.g., APMV) are in the same composition. In other embodiments, the VEGF-C agent and oncolytic virus (e.g., APMV) are in different compositions. In another embodiment, provided herein are methods for treating cancer, comprising administering to a subject in need thereof a first composition comprising an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and a second composition comprising a VEGF-C agent, wherein the method does involve administering to the subject an additional active therapy (e.g., an additional active agent) to treat cancer. In a specific embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and an effective amount of a VEGF-C agent, wherein the method does involve administering to the subject an additional active therapy (e.g., an additional active agent) to treat cancer. In a specific embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of a first composition comprising an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and an effective amount of a second composition comprising a VEGF-C agent, wherein the method does involve administering to the subject an additional active therapy (e.g., an additional active agent) to treat cancer. See Section 5.7.4 for the types of cancer that may be treated in accordance with the methods described herein, Section 5.7.3 for the types of patients that may be treated in accordance with the methods described herein, and Section 5.7.1 for exemplary dosages and regimens for treating cancer in accordance with the methods described herein. 
     In some embodiments, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof, a VEGF-C agent or a composition thereof, and one or more additional therapies, such as described in Section 5.7.2, infra. In a specific embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof, an effective amount of a VEGF-C agent or a composition thereof, and an effective amount of one or more additional therapies, such as described in Section 5.7.2, infra. In a particular embodiment, one or more therapies are administered to a subject in combination with an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof and a VEGF-C agent or a composition thereof to treat cancer. In a specific embodiment, the additional therapies are currently being used, have been used or are known to be useful in treating cancer. In another embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein) or a composition thereof and a VEGF-C agent or a composition thereof are administered to a subject in combination with a supportive therapy, a pain relief therapy, or other therapy that does not have a therapeutic effect on cancer. In certain embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), a VEGF-C agent and one or more additional therapies are administered in the same composition. In some embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein) is administered in a different composition from a VEGF-C agent and one or more additional therapies. In certain embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein) and one or more additional therapies are administered in the same composition. In some embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein) and one or more additional therapies are administered in different compositions. In certain embodiments, a VEGF-C agent and one or more additional therapies are administered in the same composition. In some embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), and a VEGF-C agent and one or more additional therapies are each administered in different compositions. An oncolytic virus, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof in combination with a VEGF-C agent and one or more additional therapies, such as described herein in Section 5.7.2, infra, may be used as any line of therapy (e.g., a first, second, third, fourth or fifth line therapy) for treating cancer in accordance with a method described herein. See Section 5.7.4 for the types of cancer that may be treated in accordance with the methods described herein, Section 5.7.3 for the types of patients that may be treated in accordance with the methods described herein, and Section 5.7.1 for exemplary dosages and regimens for treating cancer in accordance with the methods described herein. 
     In another aspect, provided herein are methods for treating cancer, comprising administering to a subject in need thereof a virus described herein (e.g., an oncolytic virus described herein) and a VEGF-C agent. The VEGF-C agent and virus may be in the same composition or different compositions, and such compositions may or may not include additional therapies, such as described in Section 5.7.2. In certain embodiments, the VEGF-D agent and oncolytic virus (e.g., APMV) are in the same composition. In other embodiments, the VEGF-D agent and oncolytic virus (e.g., APMV) are in different compositions. In some embodiments, the method further comprises administering a VEGF-C agent or a composition thereof. In another embodiment, provided herein are methods for treating cancer, comprising administering to a subject in need thereof a first composition comprising an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and a second composition comprising a VEGF-D agent. In a specific embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and an effective amount of a VEGF-D agent. In a specific embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of a first composition comprising an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and an effective amount of a second composition comprising a VEGF-D agent. See Section 5.7.4 for the types of cancer that may be treated in accordance with the methods described herein, Section 5.7.3 for the types of patients that may be treated in accordance with the methods described herein, and Section 5.7.1 for exemplary dosages and regimens for treating cancer in accordance with the methods described herein. 
     In some embodiments, provided herein are methods for treating cancer, comprising administering to a subject in need thereof an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and a VEGF-D agent, wherein the method does not involve administering to the subject an antigen (e.g., a bacterial antigen, a viral antigen, a fungal antigen, a protozoal antigen, a helminth antigen or a cancer antigen) or a composition thereof. For example, the oncolytic virus and VEGF-D agent are not administered to a subject in conjunction with an antigen (e.g., a bacterial antigen, a viral antigen, a fungal antigen, a protozoal antigen, a helminth antigen or a cancer antigen) or a composition thereof. In certain embodiments, the VEGF-D agent and oncolytic virus (e.g., APMV) are in the same composition. In other embodiments, the VEGF-D agent and oncolytic virus (e.g., APMV) are in different compositions. In some embodiments, the method further comprises administering VEGF-C or a composition thereof. In another embodiment, provided herein are methods for treating cancer, comprising administering to a subject in need thereof a first composition comprising an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and a second composition comprising a VEGF-D agent, wherein the method does involve to the subject administering an antigen (e.g., a bacterial antigen, a viral antigen, a fungal antigen, a protozoal antigen, a helminth antigen or a cancer antigen) or a composition thereof. In a specific embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and an effective amount of a VEGF-D agent, wherein the method does involve administering to the subject an antigen (e.g., a bacterial antigen, a viral antigen, a fungal antigen, a protozoal antigen, a helminth antigen or a cancer antigen) or a composition thereof. In a specific embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of a first composition comprising an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and an effective amount of a second composition comprising a VEGF-D agent, wherein the method does involve administering to the subject an antigen (e.g., a bacterial antigen, a viral antigen, a fungal antigen, a protozoal antigen, a helminth antigen or a cancer antigen) or a composition thereof. See Section 5.7.4 for the types of cancer that may be treated in accordance with the methods described herein, Section 5.7.3 for the types of patients that may be treated in accordance with the methods described herein, and Section 5.7.1 for exemplary dosages and regimens for treating cancer in accordance with the methods described herein. 
     In certain embodiments, provided herein are methods for treating cancer, comprising administering to a subject in need thereof an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and a VEGF-D agent, wherein the method does not involve administering to the subject an additional active therapy (e.g., an additional active agent) to treat cancer. In certain embodiments, the VEGF-D agent and oncolytic virus (e.g., APMV) are in the same composition. In other embodiments, the VEGF-D agent and oncolytic virus (e.g., APMV) are in different compositions. In another embodiment, provided herein are methods for treating cancer, comprising administering to a subject in need thereof a first composition comprising an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and a second composition comprising a VEGF-D agent, wherein the method does involve administering to the subject an additional active therapy (e.g., an additional active agent) to treat cancer. In a specific embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and an effective amount of a VEGF-D agent, wherein the method does involve administering to the subject an additional active therapy (e.g., an additional active agent) to treat cancer. In a specific embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of a first composition comprising an oncolytic virus described herein (e.g., a naturally occurring or recombinant APMV described herein) and an effective amount of a second composition comprising a VEGF-D agent, wherein the method does involve administering to the subject an additional active therapy (e.g., an additional active agent) to treat cancer. See Section 5.7.4 for the types of cancer that may be treated in accordance with the methods described herein, Section 5.7.3 for the types of patients that may be treated in accordance with the methods described herein, and Section 5.7.1 for exemplary dosages and regimens for treating cancer in accordance with the methods described herein. 
     In some embodiments, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof, a VEGF-D agent or a composition thereof, and one or more additional therapies, such as described in Section 5.7.2, infra. In a specific embodiment, provided herein is a method for treating cancer, comprising administering to a subject in need thereof an effective amount of an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof, an effective amount of a VEGF-D agent or a composition thereof, and an effective amount of one or more additional therapies, such as described in Section 5.7.2, infra. In a particular embodiment, one or more therapies are administered to a subject in combination with an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof and a VEGF-D agent or a composition thereof to treat cancer. In a specific embodiment, the additional therapies are currently being used, have been used or are known to be useful in treating cancer. In another embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein) or a composition thereof and a VEGF-D agent or a composition thereof are administered to a subject in combination with a supportive therapy, a pain relief therapy, or other therapy that does not have a therapeutic effect on cancer. In certain embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), a VEGF-D agent and one or more additional therapies are administered in the same composition. In some embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein) is administered in a different composition from a VEGF-D agent and one or more additional therapies. In certain embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein) and one or more additional therapies are administered in the same composition. In some embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein) and one or more additional therapies are administered in different compositions. In certain embodiments, a VEGF-D agent and one or more additional therapies are administered in the same composition. In some embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), and a VEGF-D agent and one or more additional therapies are each administered in different compositions. An oncolytic virus, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof in combination with a VEGF-D agent and one or more additional therapies, such as described herein in Section 5.7.2, infra, may be used as any line of therapy (e.g., a first, second, third, fourth or fifth line therapy) for treating cancer in accordance with a method described herein. See Section 5.7.4 for the types of cancer that may be treated in accordance with the methods described herein, Section 5.7.3 for the types of patients that may be treated in accordance with the methods described herein, and Section 5.7.1 for exemplary dosages and regimens for treating cancer in accordance with the methods described herein. 
     In a specific embodiment, provided herein are methods for treating cancer, comprising administering to a subject in need thereof a first composition as described in Section 5.6 that comprises an oncolytic virus described herein, such as an APMV described herein, and a composition as described in Section 5.6 that comprises a VEGFR-3 activating agent. In another specific embodiment, provided herein are methods for treating cancer, comprising administering to a subject in need thereof a first composition as described in Section 5.6 that comprises a oncolytic virus described herein, such as an APMV described herein, and a composition as described in Section 5.6 that comprises a VEGF-C agent. In another specific embodiment, provided herein are methods for treating cancer, comprising administering to a subject in need thereof a first composition as described in Section 5.6 that comprises a oncolytic virus described herein, such as an APMV described herein, and a second composition as described in Section 5.6 that comprises a VEGF-D agent. In another specific embodiment, provided herein are methods for treating cancer, comprising administering to a subject in need thereof a first composition as described in Section 5.6 that comprises a oncolytic virus described herein, such as an APMV described herein, a second composition as described in Section 5.6 that comprises a VEGF-C agent, and a third composition as described in Section 5.6 that comprises a VEGF-D agent. 
     An oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof may be administered locally or systemically to a subject. For example, an oncolytic virus, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof may be administered parenterally (e.g., intraperitoneally, intravenously, intra-arterially, intradermally, intramuscularly, or subcutaneously), intratumorally, intra-nodally, intrapleurally, intranasally, intracavitary, intracranially, orally, rectally, by inhalation, or topically to a subject. In a specific embodiment, an oncolytic virus, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof is administered intratumorally. Image-guidance may be used to administer an oncolytic virus, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof to the subject. In a specific embodiment, an oncolytic virus, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof is administered intravenously. 
     A VEGF-C agent or a composition thereof, or a VEGF-D agent or a composition thereof may be administered locally or systemically to a subject. For example, a VEGF-C agent or a composition thereof, or a VEGF-D agent or a composition thereof may be administered parenterally (e.g., intraperitoneally, intravenously, intra-arterially, intradermally, intramuscularly, or subcutaneously), intratumorally, intra-nodally, intrapleurally, intranasally, intracavitary, intracranially, orally, rectally, by inhalation, or topically to a subject. In a specific embodiment, a VEGF-C agent or a composition thereof, or a VEGF-D agent or a composition thereof is administered intratumorally. Image-guidance may be used to administer a VEGF-C agent or a composition thereof, or a VEGF-D agent or a composition thereof to the subject. In a specific embodiment, a VEGF-C agent or a composition thereof, or a VEGF-D agent or a composition thereof is administered intravenously. In another specific embodiment, a VEGF-C agent or a composition thereof, or a VEGF-D agent or a composition thereof is administered intradermally. 
     In certain embodiments, the methods described herein include the treatment of cancer for which no treatment is available. In some embodiments, an oncolytic virus, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof is administered to a subject to treat cancer as an alternative to other conventional therapies. Cancers that may be treated in accordance with the methods described herein include those in Section 5.7.4. 
     In certain embodiments, two, three or multiple oncolytic viruses described herein, such as APMVs (including one, two or more recombinant APMVs described herein) are administered to a subject to treat cancer. The multiple oncolytic virus administered may be the same or different. 
     In another aspect, provided herein is a method of treating cancer comprising administering to a subject in need thereof polyI:C and a VEGFR-3 activating agent described herein. In some embodiments, the polyI:C and VEGFR-3 activating agent are administered to the subject in the same composition. In other embodiments, the polyI:C and VEGFR-3 activating agent are administered in different compositions. The polyI:C or composition thereof and VEGFR-3 activating agent or composition thereof may be administered by any route known in the art or described herein. For example, the polyI:C or composition thereof may be administered to a subject subcutaneously, intravenously, intramuscularly or intratumorally. The VEGFR-3 activating agent or composition thereof may be administered to a subject subcutaneously, intravenously, intramuscularly or intratumorally. In some embodiments, the methods of treating cancer do not comprise the administration of an antigen (e.g., a cancer antigen, a bacterial antigen, a fungal antigen, a protozoal antigen, a viral antigen or a helminth antigen) to the subject. In other embodiments, the methods of treating cancer do comprise the administration of an antigen (e.g., a cancer antigen, a bacterial antigen, a fungal antigen, a protozoal antigen, a viral antigen or a helminth antigen) to the subject. In certain embodiments, the polyI:C or composition thereof and VEGFR-3 activating agent or composition thereof are the only active agents administered to a subject in accordance with the methods described herein. In other embodiments, polyI:C or composition thereof and VEGFR-3 activating agent or composition thereof are administered to a subject in combination with another therapy described herein (see, e.g., section 5.7.2). Cancers that may be treated in accordance with the methods described herein are described herein (see, e.g., Section 5.7.4). 
     In a specific embodiment, a method of treating cancer described herein may result in a beneficial effect for a subject, such as the reduction, decrease, attenuation, diminishment, stabilization, remission, suppression, inhibition or arrest of the development or progression of cancer, or a symptom thereof. In certain embodiments, a method of treating cancer described herein results in at least one, two or more of the following effects: (i) the reduction or amelioration of the severity of cancer and/or a symptom associated therewith; (ii) the reduction in the duration of a symptom associated with cancer; (iii) the prevention in the recurrence of a symptom associated with cancer; (iv) the regression of cancer and/or a symptom associated therewith; (v) the reduction in hospitalization of a subject; (vi) the reduction in hospitalization length; (vii) the increase in the survival of a subject; (viii) the inhibition of the progression of cancer and/or a symptom associated therewith; (ix) the enhancement or improvement of the therapeutic effect of another therapy; (x) a reduction or elimination in the cancer cell population; (xi) a reduction in the growth of a tumor or neoplasm; (xii) a decrease in tumor size; (xiii) a reduction in the formation of a tumor; (xiv) eradication, removal, or control of primary, regional and/or metastatic cancer; (xv) a decrease in the number or size of metastases; (xvi) a reduction in mortality; (xvii) an increase in cancer-free survival rate of patients; (xviii) an increase in relapse-free survival; (xix) an increase in the number of patients in remission; (xx) a decrease in hospitalization rate; (xxi) the size of the tumor is maintained and does not increase in size or increases the size of the tumor by less than 5% or 10% after administration of a therapy as measured by conventional methods available to one of skill in the art, such as MRI, X-ray, CT Scan and PET scan; (xxii) the prevention of the development or onset of cancer and/or a symptom associated therewith; (xxiii) an increase in the length of remission in patients; (xxiv) the reduction in the number of symptoms associated with cancer; (xxv) an increase in symptom-free survival of cancer patients; (xxvi) limitation of or reduction in metastasis; (xxvii) overall survival; (xxviii) progression-free survival (as assessed, e.g., by RECIST v1.1.); (xxix) overall response rate; and/or (xxx) an increase in response duration. In some embodiments, the treatment/therapy that a subject receives does not cure cancer, but prevents the progression or worsening of the disease. In certain embodiments, a method of treating cancer described herein does not prevent the onset/development of cancer, but may prevent the onset of cancer symptoms. Any method known to the skilled artisan may be utilized to evaluate the treatment/therapy that a subject receives. In a specific embodiment, the efficacy of a treatment/therapy is evaluated according to the Response Evaluation Criteria In Solid Tumors (“RECIST”) published rules. In a specific embodiment, the efficacy of a treatment/therapy is evaluated according to the RECIST rules published in February 2000 (also referred to as “RECIST 1”) (see, e.g., Therasse et al., 2000, Journal of National Cancer Institute, 92(3):205-216, which is incorporated by reference herein in its entirety). In a specific embodiment, the efficacy of a treatment/therapy is evaluated according to the RECIST rules published in January 2009 (also referred to as “RECIST 1.1”) (see, e.g., Eisenhauer et al., 2009, European Journal of Cancer, 45:228-247, which is incorporated by reference herein in its entirety). In a specific embodiment, the efficacy of a treatment/therapy is evaluated according to the RECIST rules utilized by the skilled artisan at the time of the evaluation. In a specific embodiment, the efficacy is evaluated according to the immune related RECIST (“irRECIST”) published rules (see, e.g., Bohnsack et al., 2014, ESMO Abstract 4958, which is incorporated by reference herein in its entirety). In a specific embodiment, the efficacy treatment/therapy is evaluated according to the irRECIST rules utilized by the skilled artisan at the time of the evaluation. In a specific embodiment, the efficacy is evaluated through a reduction in tumor-associated serum markers. 
     In some embodiments, a method for treating cancer described herein increases infiltration of one, two or all of the following cell types into a tumor: (i) T-cells, (ii) natural killer (NK) cells, and (iii) dendritic cells. In certain embodiments, a method for treating cancer described herein increases lymphocyte infiltration into a tumor. In a specific embodiments, a method for treating cancer described herein increases T cell infiltration into a tumor. In certain embodiments, a method for treating cancer described herein increases CD4+ T cell infiltration into a tumor. In some embodiments, a method for treating cancer described herein increases CD8+ T cell infiltration into a tumor. In certain embodiments, a method for treating cancer described herein increases cytokine production in a tumor (e.g., increases INFγ, IL-2, and/or TNF production). In certain embodiments, a method for treating cancer described herein increases lymphatic drainage in a tumor. In some embodiments, a method for treating cancer described herein enhances an anti-tumor cell response (e.g., an anti-tumor T-cell response, anti-tumor NKcell response, and/or an anti-tumor dendritic cell response). In a specific embodiment, a method for treating cancer described herein enhances an anti-tumor T cell response. 
     In specific embodiments, a method for treating cancer described herein increases CD8, CD4 and NK cells within a tumor, such as, e.g., described in Example 5, infra. In certain embodiments, a method for treating cancer described herein increases one, two, three or all of the following within a tumor: (i) CD4-CD8− T-cells expressing TNF-α, (ii) CD4+ T cells expressing high levels of TNF-α and IFN-γ, (iii) CD8+ T-cells expressing TNF-α, IFN-γ, and GranzymeB, and (v) NK cells expressing Granzyme B, high levels of TNF-α and dim levels of IFN-γ. In some embodiments, a method for treating cancer described herein results in an increase in CD4+ and CD8+ T cells expressing CD83 and/or CD86 in sentinel lymph nodes, such as, e.g., described in Example 5, infra. In certain embodiments, a method for treating cancer described herein increases in sentinel lymph nodes CD83+ CD4 T cells, and tumor-specific CD103+CD83+ CD86+ CD8 T cells and CD83+ CD86+Ly6c+ CD8 T cells, such as, e.g., described in Example 5, infra. In some embodiments, a method for treating cancer described herein results in the enrichment of CD8, CD4 and CD11c+ dendritic cells associated with tumor lymphatic vessels in treated tumors, such as described in Example 5, infra. In certain embodiments, a method for treating cancer described herein results in immune activation both regionally (in sentinel lymph nodes) and systemically (in contralateral lymph nodes). 
     5.7.1 Dosage and Frequency 
     The amount of an oncolytic virus, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof which will be effective in the treatment of cancer will depend on the nature of the cancer, the route of administration, the general health of the subject, etc. and should be decided according to the judgment of a medical practitioner. Standard clinical techniques, such as in vitro assays, may optionally be employed to help identify dosage ranges. However, suitable dosage ranges of an oncolytic virus, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), for administration are generally about 10 2 , 5×10 2 , 10 3 , 5×10 3 , 10 4 , 5×10 4 , 10 5 , 5×10 5 , 10 6 , 5×10 6 , 10 7 , 5×10 7 , 10 8 , 5×10 8 , 1×10 9 , 5×10 9 , 1×10 10 , 5×10 10 , 1×10 11 , 5×10 11  or 10 12  pfu, and most preferably about 10 4  to about 10 12 , 10 6  to 10 12 , 10 8  to 10 12 , 10 9  to 10 12 , 10 9  to 10 11  pfu, 10 6  to 10 10 , or 10 6  to 10 8 , and can be administered to a subject once, twice, three, four or more times with intervals as often as needed. Dosage ranges of oncolysate vaccines for administration may include 0.001 mg, 0.005 mg, 0.01 mg, 0.05 mg. 0.1 mg. 0.5 mg, 1.0 mg, 2.0 mg. 3.0 mg, 4.0 mg, 5.0 mg, 10.0 mg, 0.001 mg to 10.0 mg, 0.01 mg to 1.0 mg, 0.1 mg to 1 mg, and 0.1 mg to 5.0 mg, and can be administered to a subject once, twice, three or more times with intervals as often as needed. Dosage ranges of whole cell vaccines for administration may include 10 2 , 5×10 2 , 10 3 , 5×10 3 , 10 4 , 5×10 4 , 10 5 , 5×10 5 , 10 6 , 5×10 6 , 10 7 , 5×10 7 , 10 8 , 5×10 8 , 1×10 9 , 5×10 9 , 1×10 10 , 5×10 10 , 1×10 11 , 5×10 11  or 10 12  cells, and can be administered to a subject once, twice, three or more times with intervals as often as needed. In certain embodiments, a dosage(s) of an oncolytic virus, such as an APMV described herein, similar to a dosage(s) currently being used in clinical trials for NDV is administered to a subject. 
     In certain embodiments, an oncolytic virus, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof is administered to a subject as a single dose followed by a second dose 1 to 6 weeks, 1 to 5 weeks, 1 to 4 weeks, 1 to 3 weeks, 1 to 2 weeks later. In accordance with these embodiments, booster inoculations may be administered to the subject at 3 to 6 month or 6 to 12 month intervals following the second inoculation. 
     In certain embodiments, an oncolytic virus, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or composition thereof is administered to a subject in combination with a VEGF-C agent or a VEGF-D agent. The dosage of the VEGF-C agent or VEGF-D agent will depend upon various factors including, e.g., the therapy, the nature of the cancer, the route of administration, the general health of the subject, etc. and should be decided according to the judgment of a medical practitioner. In specific embodiments, the dose of the VEGF-C agent or VEGF-D agent is 1 mg/kg to 100 mg/kg if the agent is proteinaceous. In certain embodiments, the single dose of the VEGF-C agent or VEGF-D agent is 1 μg to 200 μg if the agent is a nucleotide sequence. In certain embodiments, a therapeutically effective dose is administered. In specific embodiments, a therapeutically effective dose of the VEGF-C agent or VEGF-D agent is 1 mg/kg to 100 mg/kg if the agent is proteinaceous. In specific embodiments, a therapeutically effective dose of the VEGF-C agent or VEGF-D agent is 1 μg to 200 μg if the agent is a nucleotide sequence. 
     In certain embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or composition thereof is administered to a subject concurrently with the administration of a VEGF-C agent or VEGF-D agent. In other embodiments, an oncolytic virus described herein, such as an APMV described (e.g., a naturally occurring or recombinant APMV described herein), or composition thereof is administered to a subject every 3 to 7 days, 1 to 6 weeks, 1 to 5 weeks, 1 to 4 weeks, 2 to 4 weeks, 1 to 3 weeks, or 1 to 2 weeks and a VEGF-C agent or a VEGF-D agent is administered every 3 to 7 days, 1 to 6 weeks, 1 to 5 weeks, 1 to 4 weeks, 1 to 3 weeks, or 1 to 2 weeks. In certain embodiments, an oncolytic virus described herein, such as an APMV described (e.g., a naturally occurring or recombinant APMV described herein), or composition thereof is administered to a subject every day. In certain embodiments, an oncolytic virus described herein, such as an APMV described (e.g., a naturally occurring or recombinant APMV described herein), or composition thereof is administered to a subject every other day. 
     In certain embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or composition thereof is administered to a subject before or after the administration of a VEGF-C agent or VEGF-D agent. In other embodiments, an oncolytic virus described herein, such as an APMV described (e.g., a naturally occurring or recombinant APMV described herein), or composition thereof is administered to a subject 1 to 3 weeks, 2 weeks, 1 month, 2 months, or 3 months before or after a VEGF-C agent or a VEGF-D agent is administered. In other embodiments, an oncolytic virus described herein, such as an APMV described (e.g., a naturally occurring or recombinant APMV described herein), or composition thereof is administered to a subject 1, 2, 3, 4, 5, or 6 days before or after a VEGF-C agent or a VEGF-D agent is administered. In some embodiments, no additional therapies are administered to a subject (e.g., human subject) during the timeframe that the subject is receiving a VEGF-C agent or a VEGF-D agent and an oncolytic virus described herein, such as an APMV described (e.g., a naturally occurring or recombinant APMV described herein), or composition thereof. In other embodiments, one or more additional therapies, such as a therapy described in Section 5.7.2, infra, are administered to a subject (e.g., human subject) during the timeframe that the subject is receiving a VEGF-C agent or a VEGF-D agent and an oncolytic virus described herein, such as an APMV described (e.g., a naturally occurring or recombinant APMV described herein), or composition thereof. 
     In certain embodiments, an oncolytic virus, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or composition thereof is administered to a subject in combination with one or more additional therapies, such as a therapy described in Section 5.7.2, infra. The dosage of the other one or more additional therapies will depend upon various factors including, e.g., the therapy, the nature of the cancer, the route of administration, the general health of the subject, etc. and should be decided according to the judgment of a medical practitioner. In specific embodiments, the dose of the other therapy is the dose and/or frequency of administration of the therapy recommended for the therapy for use as a single agent is used in accordance with the methods disclosed herein. In other embodiments, the dose of the other therapy is a lower dose and/or involves less frequent administration of the therapy than recommended for the therapy for use as a single agent is used in accordance with the methods disclosed herein. Recommended doses for approved therapies can be found in the Physicians&#39; Desk Reference (e.g., the 71 st  ed. of the Physicians&#39; Desk Reference (2017)). 
     In certain embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or composition thereof is administered to a subject concurrently with the administration of one or more additional therapies. In other embodiments, an oncolytic virus described herein, such as an APMV described (e.g., a naturally occurring or recombinant APMV described herein), or composition thereof is administered to a subject every 3 to 7 days, 1 to 6 weeks, 1 to 5 weeks, 1 to 4 weeks, 2 to 4 weeks, 1 to 3 weeks, or 1 to 2 weeks and one or more additional therapies (such as described in Section 5.6.2, infra) is administered every 3 to 7 days, 1 to 6 weeks, 1 to 5 weeks, 1 to 4 weeks, 1 to 3 weeks, or 1 to 2 weeks. 
     5.7.2 Additional Therapies 
     Additional therapies that can be used in a combination with an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof for the treatment of cancer include, but are not limited to, small molecules, synthetic drugs, peptides (including cyclic peptides), polypeptides, proteins, nucleic acids (e.g., DNA and RNA nucleotides including, but not limited to, antisense nucleotide sequences, triple helices, RNAi, and nucleotide sequences encoding biologically active proteins, polypeptides or peptides), antibodies, synthetic or natural inorganic molecules, mimetic agents, and synthetic or natural organic molecules. In a specific embodiment, the additional therapy is a chemotherapeutic agent. In a specific embodiment, an additional therapy described herein may be used in combination with an oncolysate or whole cell vaccine described herein. 
     In some embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein) or a composition thereof is used in combination with radiation therapy comprising the use of x-rays, gamma rays and other sources of radiation to destroy cancer cells. In specific embodiments, the radiation therapy is administered as external beam radiation or teletherapy, wherein the radiation is directed from a remote source. In other embodiments, the radiation therapy is administered as internal therapy or brachytherapy wherein a radioactive source is placed inside the body close to cancer cells and/or a tumor mass. 
     Specific examples of anti-cancer agents that may be used in combination with an oncolytic virus described herein, such as an APMV described herein, or a composition thereof include: hormonal agents (e.g., aromatase inhibitor, selective estrogen receptor modulator (SERM), and estrogen receptor antagonist), chemotherapeutic agents (e.g., microtubule disassembly blocker, antimetabolite, topoisomerase inhibitor, and DNA crosslinker or damaging agent), radiation therapy, and conventional surgery. 
     In particular embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof is used in combination with an immunomodulatory agent. In a specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring APMV or a recombinant APMV described herein), or composition thereof is used in combination with an agonist of a co-stimulatory receptor found on immune cells, such as, e.g., T-lymphocytes (e.g., CD4+ or CD8+ T-lymphocytes), NK cells and/or antigen-presenting cells (e.g., dendritic cells or macrophages), or a composition thereof. Specific examples of co-stimulatory receptors include glucocorticoid-induced tumor necrosis factor receptor (GITR), Inducible T-cell costimulator (ICOS or CD278), OX40 (CD134), CD27, CD28, 4-1BB (CD137), CD40, lymphotoxin alpha (LT alpha), LIGHT (lymphotoxin-like, exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for HVEM, a receptor expressed by T lymphocytes), CD226, cytotoxic and regulatory T cell molecule (CRTAM), death receptor 3 (DR3), lymphotoxin-beta receptor (LTBR), transmembrane activator and CAML interactor (TACI), B cell-activating factor receptor (BAFFR), and B cell maturation protein (BCMA). In a specific embodiment, the agonist of the co-stimulatory molecule binds to a receptor on a cell (e.g., GITR, ICOS, OX40, CD70, 4-1BB, CD40, LIGHT, etc.) and triggers or enhances one or more signal transduction pathways. In a particular embodiment, the agonist of the co-stimulatory receptor is an antibody or ligand that binds to the co-stimulatory receptor and induces or enhances one or more signal transduction pathways. In certain embodiments, the agonist facilitates the interaction between a co-stimulatory receptor and its ligand(s). In certain embodiments, the agonist of a co-stimulatory receptor is an antibody (e.g., monoclonal antibody) that binds to glucocorticoid-induced tumor necrosis factor receptor (GITR), Inducible T-cell costimulator (ICOS or CD278), OX40 (CD134), CD27, CD28, 4-1BB (CD137), CD40, lymphotoxin alpha (LT alpha), LIGHT (lymphotoxin-like, exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for HVEM, a receptor expressed by T lymphocytes), CD226, cytotoxic and regulatory T cell molecule (CRTAM), death receptor 3 (DR3), lymphotoxin-beta receptor (LTBR), transmembrane activator and CAML interactor (TACI), B cell-activating factor receptor (BAFFR), or B cell maturation protein (BCMA). In a specific embodiment, the agonist of a co-stimulatory receptor is an antibody (e.g., monoclonal antibody) that binds to 4-1BB or OX40. 
     In a specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof is used in combination with an antagonist of an inhibitory receptor found on immune cells, such as, e.g., T-lymphocytes (e.g., CD4+ or CD8+ T-lymphocytes), NK cells and/or antigen-presenting cells (e.g., dendritic cells or macrophages), or a composition thereof. Specific examples of inhibitory receptors include cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4 or CD52), programmed cell death protein 1 (PD-1 or CD279), B and T-lymphocyte attenuator (BTLA), killer cell immunoglobulin-like receptor (KIR), lymphocyte activation gene 3 (LAG3), T-cell membrane protein 3 (TIM3), CD160, adenosine A2a receptor (A2aR), T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT), leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), and CD160. In a specific embodiment, the antagonist inhibits the action of the inhibitory receptor without provoking a biological response itself. In a specific embodiment, the antagonist is an antibody or ligand that binds to an inhibitor receptor on an immune cell and blocks or dampens binding of the receptor to one or more of its ligands. In a particular embodiment, the antagonist of an inhibitory receptor is an antibody or a soluble receptor that specifically binds to the ligand for the inhibitory receptor and blocks the ligand from binding to the inhibitory receptor and transducing an inhibitory signal(s). Specific examples of ligands for inhibitory receptors include PD-L1, PD-L2, B7-H3, B7-H4, HVEM, Gal9 and adenosine. Specific examples of inhibitory receptors include CTLA-4, PD-1, BTLA, KIR, LAG3, TIM3, and A2aR. 
     In specific embodiments, the antagonist of an inhibitory receptor is a soluble receptor that specifically binds to a ligand for the inhibitory receptor and blocks the ligand from binding to the inhibitory receptor and transducing an inhibitory signal(s). In certain embodiments, the soluble receptor is a fragment of an inhibitory receptor (e.g., the extracellular domain of an inhibitory receptor). In some embodiments, the soluble receptor is a fusion protein comprising at least a portion of the inhibitory receptor (e.g., the extracellular domain of the native inhibitory receptor), and a heterologous amino acid sequence. In specific embodiments, the fusion protein comprises at least a portion of the inhibitory receptor, and the Fc portion of an immunoglobulin or a fragment thereof. In a specific embodiment, the antagonist of an inhibitory receptor is a LAG3-Ig fusion protein (e.g., IMP321). 
     In another embodiment, the antagonist of an inhibitory receptor is an antibody that specifically binds to a ligand(s) of the inhibitory receptor and blocks the ligand(s) from binding to the inhibitory receptor and transducing an inhibitory signal(s). Specific examples of ligands for inhibitory receptors include PD-L1, PD-L2, B7-H3, B7-H4, HVEM, Gal9 and adenosine. Specific examples of inhibitory receptors include CTLA-4, PD-1, BTLA, KIR, LAG3, and A2aR. In a specific embodiment, the antagonist is an antibody that binds to PD-L1 or PD-L2. 
     In another embodiment, the antagonist of an inhibitory receptor is an antibody that binds to the inhibitory receptor and blocks the binding of the inhibitory receptor to one, two or more of its ligands. In a specific embodiment, the binding of the antibody to the inhibitory receptor does not transduce an inhibitory signal(s) or blocks an inhibitory signal(s). Specific examples of inhibitory receptors include CTLA-4, PD-1, BTLA, KIR, LAG3, TIM3, and A2aR. A specific example of an antibody to inhibitory receptor is anti-CTLA-4 antibody (Leach D R, et al. Science 1996; 271: 1734-1736). In a specific embodiment, an antagonist of an inhibitory receptor is an antagonist of CTLA-4, such as, e.g., Ipilimumab or Tremelimumab. 
     In certain embodiments, the antagonist of an inhibitory receptor is an antagonist of PD-1, such as, e.g., Nivolumab (MDX-1106 or BMS-936558), pembrolizumab (MK3475), pidlizumab (CT-011), AMP-224 (a PD-L2 fusion protein), Atezoliuzumab (MPDL3280A; anti-PD-L1 monoclonal antibody), Avelumab (an anti-PD-L1 monoclonal antibody) or MDX-1105 (an anti-PD-L1 monoclonal antibody). In certain embodiments, an antagonist of an inhibitory receptor is an antagonist of LAG3, such as, e.g., IMP321. 
     In a specific embodiment, an antagonist of an inhibitory receptor is an anti-PD-1 antibody that blocks the interaction between PD-1 and its ligands (PD-L1 and PD-L2). Non-limiting examples of antibodies that bind to PD-1 include pembrolizumab (“KEYTRUDA®”; see, e.g., Hamid et al., N Engl J Med. 2013; 369:134-44 and Full Prescribing Information for KEYTRUDA, Reference ID: 3862712), nivolumab (“OPDIVO®”; see, e.g., Topalian et al., N Engl J Med. 2012; 366:2443-54 and Full Prescribing Information for OPDIVO (nivolumab), Reference ID: 3677021), and MEDI0680 (also referred to as “AMP-514”; see, e.g., Hamid et al., Ann Oncol. 2016; 27(suppl_6):1050PD). In a specific embodiment, the antagonist of an inhibitory receptor is an anti-PD1 antibody (e.g., pembrolizumab). 
     In a specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof is used in combination with a checkpoint inhibitor. In a specific embodiment, the checkpoint inhibitor may be an antibody that binds to an inhibitory receptor found on a T cell, such as PD-1, CTLA-4, LAG-3, or TIM-3. In another specific embodiment, the checkpoint inhibitor may be an antibody that binds to an inhibitory receptor found on a T cell, such as PD-1, CTLA-4, LAG-3, or TIM-3 and blocks binding of the inhibitory receptor to its ligand(s). 
     In a specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof is used in combination with an anti-PD1 antibody that blocks binding of PD1 to its ligand(s) (e.g., either PD-L1, PD-L2, or both), such as described herein or known to one of skill in the art, or a composition thereof. In a specific embodiment, the antibody is a monoclonal antibody. 
     In a specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof is used in combination with an anti-PD-L1 antibody (e.g., an anti-PD-L1 antibody described herein or known to one of skill in art), or a composition thereof. In a specific embodiment, the antibody is a monoclonal antibody. 
     In a specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof is used in combination with an anti-PD-L2 antibody (e.g., an anti-PD-L2 antibody described herein or known to one of skill in art), or a composition thereof. In a specific embodiment, the antibody is a monoclonal antibody. In a specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof is used in combination with a RIG-1 agonist (e.g., poly-dA-dT (otherwise known as poly(deoxyadenylic-deoxythymidylic) acid sodium salt)), or a composition thereof. In another specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof is used in combination with an MDA-5 agonist or a composition thereof. In another specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof is used in combination with a NOD1/NOD2 agonist (e.g., MurNAc-L-Ala-γ-D-Glu-mDAP) or a composition thereof. In another specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof is used in combination with an agent that activates cGAS/STING signalling (e.g., cGAMP, such as 2′3′ cGAMP) or a composition thereof. In another specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof is used in combination with Toll-like receptor agonist (e.g., BCG, PolyI:C, Poly ICLC, MPL, Imiquimod, CpG ODN (see, e.g., Braunstein et al., 2018, Target Oncol. 13(5):583-598 for examples of such agents)) or a composition thereof. In another specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof is used in combination with an antibody that specifically binds to CD3 or a composition thereof. 
     Currently available cancer therapies and their dosages, routes of administration and recommended usage are known in the art and have been described in such literature as the Physicians&#39; Desk Reference (71st ed., 2017). 
     5.7.3 Patient Population 
     In some embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof, or a combination therapy described herein is administered to a subject suffering from cancer. In other embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof, or a combination therapy described herein is administered to a subject predisposed or susceptible to cancer. In some embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein) or a composition thereof, or a combination therapy described herein is administered to a subject diagnosed with cancer. Specific examples of the types of cancer are described herein (see, e.g., Section 5.6.4 and Section 6). In an embodiment, the subject has metastatic cancer. In another embodiment, the subject has stage 1, stage 2, stage 3, or stage 4 cancer. In another embodiment, the subject is in remission. In yet another embodiment, the subject has a recurrence of cancer. 
     In certain embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof, or a combination therapy described herein is administered to a human that is 0 to 6 months old, 6 to 12 months old, 6 to 18 months old, 18 to 36 months old, 1 to 5 years old, 5 to 10 years old, 10 to 15 years old, 15 to 20 years old, 20 to 25 years old, 25 to 30 years old, 30 to 35 years old, 35 to 40 years old, 40 to 45 years old, 45 to 50 years old, 50 to 55 years old, 55 to 60 years old, 60 to 65 years old, 65 to 70 years old, 70 to 75 years old, 75 to 80 years old, 80 to 85 years old, 85 to 90 years old, 90 to 95 years old or 95 to 100 years old. In some embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof, or a combination therapy described herein is administered to a human infant. In other embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof, or a combination therapy described herein is administered to a human toddler. In other embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g. a naturally occurring or recombinant APMV described herein), or a composition thereof, or a combination therapy described herein is administered to a human child. In other embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein)m or a composition thereof, or a combination therapy described herein is administered to a human adult. In yet other embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof, or a combination therapy described herein is administered to an elderly human. 
     In certain embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof, or a combination therapy described herein is administered to a subject in an immunocompromised state or immunosuppressed state or at risk for becoming immunocompromised or immunosuppressed. In certain embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof, or a combination therapy described herein is administered to a subject receiving or recovering from immunosuppressive therapy. In certain embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof, or a combination therapy described herein is administered to a subject that has or is at risk of getting cancer. In certain embodiments, the subject is, will or has undergone surgery, chemotherapy and/or radiation therapy. In certain embodiments, the patient has undergone surgery to remove the tumor or neoplasm. In specific embodiments, the patient is administered an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof, or a combination therapy described herein following surgery to remove a tumor or neoplasm. In other embodiments, the patient is administered an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof, or a combination therapy described herein prior to undergoing surgery to remove a tumor or neoplasm. In certain embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof, or a combination therapy described herein is administered to a subject that has, will have or had a tissue transplant, organ transplant or transfusion. 
     In some embodiments, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof, or a combination therapy described herein is administered to a patient who has proven refractory to therapies other than the oncolytic virus (e.g., APMV) or composition thereof, or a combination therapy but are no longer on these therapies. In a specific embodiment, an oncolytic virus described herein, such as an APMV described herein (e.g., a naturally occurring or recombinant APMV described herein), or a composition thereof, or a combination therapy described herein is administered to a patient who has proven refractory to chemotherapy. The determination of whether cancer is refractory can be made by any method known in the art. In a certain embodiment, refractory patient is a patient refractory to a standard therapy. In some embodiments, a patient with cancer is initially responsive to therapy, but subsequently becomes refractory. 
     In certain embodiments, a cancer treated in accordance with the methods described herein has low levels of or no detectable levels of VEGF-C expression, as assessed by determining the level of expression of VEGF-C in a tumor biopsy sample using techniques known to one of skill in the art, such as immunohistochemistry, ELISA, RNA-seq or qPCR. In some embodiments, a cancer treated in accordance with the methods described herein has moderate to high levels of VEGF-C expression, as assessed by determining the level of expression of VEGF-C by tumor biopsy sample using techniques known to one of skill in the art, such as immunohistochemistry, ELISA, RNA-seq or qPCR. Low, moderate or high levels of VEGF-C may be determined by comparison to a healthy donor control sample or can be expressed as relative to other cancers of the same type in the patient population. In a specific embodiment, a transcriptome from a patient is compared to transcriptomes from healthy tissue samples from healthy control subjects or to transcriptomes from tumor biopsies of patients with the same or similar type of cancer using, e.g., data from the Genotype-Tissue Expression project (GTEX), The Cancer Genome Atlas (TCGA), or both. 
     In certain embodiments, a cancer treated in accordance with the methods described herein has low levels of or no detectable levels of VEGF-D expression, as assessed by determining the level of expression of VEGF-D in a tumor biopsy sample using techniques known to one of skill in the art, such as immunohistochemistry, ELISA, RNA-seq or qPCR. In some embodiments, a cancer treated in accordance with the methods described herein has moderate to high levels of VEGF-D expression, as assessed by determining the level of expression of VEGF-D by tumor biopsy sample using techniques known to one of skill in the art, such as immunohistochemistry, ELISA, RNA-seq or qPCR. Low, moderate or high levels of VEGF-D may be determined by comparison to a healthy donor control sample or can be expressed as relative to other cancers of the same type in the patient population. In a specific embodiment, a transcriptome from a patient is compared to transcriptomes from healthy tissue samples from healthy control subjects or to transcriptomes from tumor biopsies of patients with the same or similar type of cancer using, e.g., data from the Genotype-Tissue Expression project (GTEX), The Cancer Genome Atlas (TCGA), or both. 
     5.7.4 Types of Cancers 
     Specific examples of cancers that can be treated in accordance with the methods described herein include, but are not limited to: melanomas, leukemias, lymphomas, multiple myelomas, sarcomas, and carcinomas. In one embodiment, cancer treated in accordance with the methods described herein is a leukemia, such as acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemias, such as, myeloblastic, promyelocytic, myelomonocytic, monocytic, erythroid leukemias, and myelodysplastic syndrome. In another embodiment, cancer treated in accordance with the methods described herein is a chronic leukemia, such as chronic myelocytic (granulocytic) leukemia, chronic lymphocytic leukemia, and hairy cell leukemia. In another embodiment, cancer treated in accordance with the methods described herein is a lymphoma, such as Hodgkin disease and non-Hodgkin disease. In another embodiment, cancer treated in accordance with the methods described herein is a multiple myeloma such as smoldering multiple myeloma, nonsecretory myeloma, osteosclerotic myeloma, solitary plasmacytoma and extramedullary plasmacytoma. In another embodiment, cancer treated in accordance with the methods described herein is Waldenström&#39;s macroglobulinemia monoclonal gammopathy of undetermined significance, benign monoclonal gammopathy, Wilm&#39;s tumor, or heavy chain disease 
     In one embodiment, cancer treated in accordance with the methods described herein is bone cancer, brain cancer, breast cancer, adrenal cancer, thyroid cancer, pancreatic cancer, pituitary cancer, eye cancer, vaginal, vulvar cancer, cervical cancer, uterine cancer, ovarian cancer, esophageal cancer, stomach cancer, colon cancer, rectal cancer, liver cancer, gallbladder cancer, lung cancer, testicular cancer, prostate cancer, penal cancer, oral cancer, basal cancer, salivary gland cancer, pharynx cancer, skin cancer, kidney cancer, or bladder cancer. In another embodiment, cancer treated in accordance with the methods described herein is brain, breast, lung, colorectal, liver, kidney or skin cancer. 
     In another embodiment, cancer treated in accordance with the methods described herein is a bone and connective tissue sarcoma, such as bone sarcoma, osteosarcoma, chondrosarcoma, Ewing&#39;s sarcoma, malignant giant cell tumor, fibrosarcoma of bone, chordoma, periosteal sarcoma, soft-tissue sarcomas, angiosarcoma (hemangiosarcoma), fibrosarcoma, Kaposi&#39;s sarcoma, leiomyosarcoma, liposarcoma, lymphangiosarcoma, neurilemmoma, rhabdomyosarcoma, or synovial sarcoma. In another embodiment, cancer treated in accordance with the methods described herein is a brain tumor, such as glioma, astrocytoma, brain stem glioma, ependymoma, oligodendroglioma, nonglial tumor, glioblastoma multiforme, acoustic neurinoma, craniopharyngioma, medulloblastoma, meningioma, pineocytoma, pineoblastoma, or primary brain lymphoma. In another embodiment, cancer treated in the accordance with the methods described herein is breast cancer, such as triple negative breast cancer, ER+/HER2-breast cancer, ER+/PR+/HER2+ breast cancer, ER−/PR−/Her2− breast cancer, ductal carcinoma, adenocarcinoma, lobular (cancer cell) carcinoma, intraductal carcinoma, medullary breast cancer, mucinous breast cancer, tubular breast cancer, papillary breast cancer, Paget&#39;s disease, or inflammatory breast cancer. In another embodiment, cancer treated in the accordance with the methods described herein is adrenal cancer, such as pheochromocytom or adrenocortical carcinoma. In another embodiment, cancer treated in the accordance with the methods described herein is thyroid cancer, such as papillary or follicular thyroid cancer, medullary thyroid cancer or anaplastic thyroid cancer. In another embodiment, cancer treated in the accordance with the methods described herein is pancreatic cancer, such as insulinoma, gastrinoma, glucagonoma, vipoma, somatostatin-secreting tumor, or carcinoid or islet cell tumor. In another embodiment, cancer treated in the accordance with the methods described herein is pituitary cancer, such as Cushing&#39;s disease, prolactin-secreting tumor, acromegaly, or diabetes insipidus. In another embodiment, cancer treated in the accordance with the methods described herein is eye cancer, such as ocular melanoma such as iris melanoma, choroidal melanoma, ciliary body melanoma, or retinoblastoma. In another embodiment, cancer treated in the accordance with the methods described herein is vaginal cancer, such as squamous cell carcinoma, adenocarcinoma, or melanoma. In another embodiment, cancer treated in the accordance with the methods described herein is vulvar cancer, such as squamous cell carcinoma, melanoma, adenocarcinoma, basal cell carcinoma, sarcoma, or Paget&#39;s disease. In another embodiment, cancer treated in the accordance with the methods described herein is cervical cancer, such as squamous cell carcinoma or adenocarcinoma. In another embodiment, cancer treated in the accordance with the methods described herein is uterine cancer, such as endometrial carcinoma or uterine sarcoma. 
     In another embodiment, cancer treated in accordance with the methods described herein is ovarian cancer, such as ovarian epithelial carcinoma, borderline tumor, germ cell tumor, or stromal tumor. In another embodiment, cancer treated in accordance with the methods described herein is esophageal cancer, such as squamous cancer, adenocarcinoma, adenoid cystic carcinoma, mucoepidermoid carcinoma, adenosquamous carcinoma, sarcoma, melanoma, placancercytoma, verrucous carcinoma, or oat cell (cancer cell) carcinoma. In another embodiment, cancer treated in accordance with the methods described herein is stomach cancer, such as adenocarcinoma, fungating (polypoid), ulcerating, superficial spreading, diffusely spreading, malignant lymphoma, liposarcoma, fibrosarcoma, or carcinosarcoma. In another embodiment, cancer treated in accordance with the methods described herein is liver cancer, such as hepatocellular carcinoma or hepatoblastoma. In another embodiment, cancer treated in accordance with the methods described herein is gallbladder cancer, such as adenocarcinoma. In another embodiment, cancer treated in accordance with the methods described herein is cholangiocarcinoma, such as papillary, nodular, or diffuse. In another embodiment, cancer treated in accordance with the methods described herein is lung cancer, such as non-small cell lung cancer, squamous cell carcinoma (epidermoid carcinoma), adenocarcinoma, large-cell carcinoma or cancer-cell lung cancer. In another embodiment, cancer treated in accordance with the methods described herein is testicular cancer, such germinal tumor, seminoma, anaplastic, classic (typical), spermatocytic, nonseminoma, embryonal carcinoma, teratoma carcinoma, or choriocarcinoma (yolk-sac tumor). In another embodiment, cancer treated in accordance with the methods described herein is prostate cancer, such as prostatic intraepithelial neoplasia, adenocarcinoma, leiomyosarcoma, or rhabdomyosarcoma. In another embodiment, cancer treated in accordance with the methods described herein is penal cancers. In another embodiment, cancer treated in accordance with the methods described herein is oral cancer, such as squamous cell carcinoma. In another embodiment, cancer treated in accordance with the methods described herein is salivary gland cancer, such as adenocarcinoma, mucoepidermoid carcinoma, or adenoidcystic carcinoma. In another embodiment, cancer treated in accordance with the methods described herein is pharynx cancer, such as squamous cell cancer or verrucous. In another embodiment, cancer treated in accordance with the methods described herein is skin cancer, such as basal cell carcinoma, squamous cell carcinoma and melanoma, superficial spreading melanoma, nodular melanoma, lentigo malignant melanoma, or acral lentiginous melanoma. In another embodiment, cancer treated in accordance with the methods described herein is kidney cancer, such as renal cell carcinoma, adenocarcinoma, hypernephroma, fibrosarcoma, or transitional cell cancer (renal pelvis and/or uterine). In another embodiment, cancer treated in accordance with the methods described herein is bladder cancer, such as transitional cell carcinoma, squamous cell cancer, adenocarcinoma, or carcinosarcoma. 
     In a specific embodiment, the cancer treated in accordance with the methods described herein is a melanoma. In another specific embodiment, the cancer treated in accordance with the methods described herein is a lung carcinoma. In another specific embodiment, the cancer treated in accordance with the methods described herein is a colorectal carcinoma. In a specific embodiment, the cancer treated in accordance with the methods described herein is melanoma, non-small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, urothelial carcinoma, microsatellite instability-high cancer, gastric cancer, or cervical cancer. 
     In a specific embodiment, an oncolytic virus described herein (e.g., an AMPV) or compositions thereof, or a combination therapy described herein are useful in the treatment of a variety of cancers and abnormal proliferative diseases, including (but not limited to) the following: carcinoma, including that of the bladder, breast, colon, kidney, liver, lung, ovary, pancreas, stomach, cervix, thyroid and skin; including squamous cell carcinoma; hematopoietic tumors of lymphoid lineage, including leukemia, acute lymphocytic leukemia, acute lymphoblastic leukemia, B-cell lymphoma, T cell lymphoma, Burkitt&#39;s lymphoma; hematopoietic tumors of myeloid lineage, including acute and chronic myelogenous leukemias and promyelocytic leukemia; tumors of mesenchymal origin, including fibrosarcoma and rhabdomyoscarcoma; other tumors, including melanoma, seminoma, teratocarcinoma, neuroblastoma and glioma; tumors of the central and peripheral nervous system, including astrocytoma, neuroblastoma, glioma, and schwannomas; tumors of mesenchymal origin, including fibrosarcoma, rhabdomyoscarama, and osteosarcoma; and other tumors, including melanoma, xeroderma pigmentosum, keratoactanthoma, seminoma, thyroid follicular cancer and teratocarcinoma. 
     In some embodiments, cancers associated with aberrations in apoptosis are treated in accordance with the methods described herein. Such cancers may include, but are not limited to, follicular lymphomas, carcinomas with p53 mutations, hormone dependent tumors of the breast, prostate and ovary, and precancerous lesions such as familial adenomatous polyposis, and myelodysplastic syndromes. In specific embodiments, malignancy or dysproliferative changes (such as metaplasias and dysplasias), or hyperproliferative disorders of the skin, lung, liver, bone, brain, stomach, colon, breast, prostate, bladder, kidney, pancreas, ovary, uterus or any combination of the foregoing are treated in accordance with the methods described herein. In other specific embodiments, a sarcoma or melanoma is treated in accordance with the methods described herein. 
     In a specific embodiment, the cancer being treated in accordance with the methods described herein is leukemia, lymphoma or myeloma (e.g., multiple myeloma). Specific examples of leukemias and other blood-borne cancers that can be treated in accordance with the methods described herein include, but are not limited to, acute lymphoblastic leukemia “ALL”, acute lymphoblastic B-cell leukemia, acute lymphoblastic T-cell leukemia, acute myeloblastic leukemia “AML”, acute promyelocytic leukemia “APL”, acute monoblastic leukemia, acute erythroleukemic leukemia, acute megakaryoblastic leukemia, acute myelomonocytic leukemia, acute nonlymphocyctic leukemia, acute undifferentiated leukemia, chronic myelocytic leukemia “CIVIL”, chronic lymphocytic leukemia “CLL”, and hairy cell leukemia. 
     Specific examples of lymphomas that can be treated in accordance with the methods described herein include, but are not limited to, Hodgkin disease, non-Hodgkin lymphoma such as diffuse large B-cell lymphoma, multiple myeloma, Waldenström&#39;s macroglobulinemia, heavy chain disease, and polycythemia vera. 
     In another embodiment, the cancer being treated in accordance with the methods described herein is a solid tumor. Examples of solid tumors that can be treated in accordance with the methods described herein include, but are not limited to fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing&#39;s tumor, leiomyosarcoma, rhabdomyosarcoma, colon cancer, colorectal cancer, kidney cancer, pancreatic cancer, bone cancer, breast cancer, ovarian cancer, prostate cancer, esophageal cancer, stomach cancer, oral cancer, nasal cancer, throat cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms&#39; tumor, cervical cancer, uterine cancer, testicular cancer, cancer cell lung carcinoma, bladder carcinoma, lung cancer, epithelial carcinoma, glioma, glioblastoma multiforme, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, meningioma, skin cancer, melanoma, neuroblastoma, and retinoblastoma. In another embodiment, the cancer being treated in accordance with the methods described herein is a metastatic. In another embodiment, the cancer being treated in accordance with the methods described herein is malignant. 
     In a specific embodiment, the cancer being treated in accordance with the methods described herein is a cancer that has a poor prognosis and/or has a poor response to conventional therapies, such as chemotherapy and radiation. In another specific embodiment, the cancer being treated in accordance with the methods described herein is malignant melanoma, malignant glioma, renal cell carcinoma, pancreatic adenocarcinoma, malignant pleural mesothelioma, lung adenocarcinoma, lung small cell carcinoma, lung squamous cell carcinoma, anaplastic thyroid cancer, or head and neck squamous cell carcinoma. In another specific embodiment, the cancer being treated in accordance with the methods described herein is a type of cancer described in Section 6, infra. 
     In a specific embodiment, the cancer being treated in accordance with the methods described herein is a cancer that is metastatic. In a specific embodiment, the cancer comprises a dermal, subcutaneous, or nodal metastasis. In a specific embodiment, the cancer comprises peritoneal or pleural metastasis. In a specific embodiment, the cancer comprises visceral organ metastasis, such as liver, kidney, spleen, or lung metastasis. 
     In a specific embodiment, the cancer being treated in accordance with the methods described herein is a cancer that is unresectable. Any method known to the skilled artisan may be utilized to determine if a cancer is unresectable. 
     5.8 Biological Assays 
     In a specific embodiment, one, two or more of the assays described in Section 6 may be used to characterize an oncolytic virus described herein, such as an APMV described herein. In certain embodiments, the expression, the activity (e.g., one, two or more functions), or both of a VEGFR-3 activating agent is determined using techniques known to one of skill in the art. In certain embodiments, the expression, the activity (e.g., one, two or more functions), or both of a VEGF-C agent is determined using techniques known to one of skill in the art. In some embodiments, the expression, the activity (e.g., one, two or more functions), or both of a VEGF-D agent is determined using techniques known to one of skill in the art. For example, the expression of a VEGF-C or VEGF-D agent may be determined using a qPCR or an immunoassay, such as a Western Blot, an ELISA or immunohistochemistry. The ability of VEGF-C or VEGF-D agent to bind to VEGFR-3 and VEGFR-2, may be determined using techniques known in the art. The ability of a VEGFR-3 activating agent to induce phosphorylation of VEGFR-3 and downstream phosphorylation of serine/threonine kinases, such as, e.g., AKT, ERK1/2 and Stat3 may be determined using techniques known in the art, such as Western blotting or protein arrays. The ability of a VEGFR-3 activating agent to modulate proliferation of cells may be determined using techniques known in the art, such as growth assays or clonogenic survival assays. The ability of a VEGFR-3 activating agent to modulate migration of cells may be determined using techniques known in the art, such as transwell migration assays and scratch assays. The ability of a VEGFR-3 activating agent to modulate tube formation of lymphatic endothelial cells may be determined using techniques known in the art. See, e.g., Nowak-Sliwinska et al., 2018, Angiogenesis 21: 425-532; Oliver et al., Oliver G., Kahn M. (eds) Lymphangiogenesis. Methods in Molecular Biology, 2018, vol 1846. Humana Press, New York, N.Y.; and Gibot et al., 2016, Biomaterials 78:129-39 for examples of assays. 
     5.8.1 In Vitro Assays 
     Viral assays include those that indirectly measure viral replication (as determined, e.g., by plaque formation) or the production of viral proteins (as determined, e.g., by western blot analysis) or viral RNAs (as determined, e.g., by RT-PCR or northern blot analysis) in cultured cells in vitro using methods which are well known in the art. 
     Growth of an oncolytic virus described herein, such as an APMV described herein, can be assessed by any method known in the art or described herein (e.g., in cell culture (e.g., cultures of chicken embryonic kidney cells or cultures of chicken embryonic fibroblasts (CEF)) (see, e.g., Section 6). Viral titer may be determined by inoculating serial dilutions of a recombinant APMV described herein into cell cultures (e.g., CEF, MDCK, EFK-2 cells, Vero cells, primary human umbilical vein endothelial cells (HUVEC), H292 human epithelial cell line or HeLa cells), chick embryos, or live animals (e.g., avians). After incubation of the virus for a specified time, the virus is isolated using standard methods. Physical quantitation of the virus titer can be performed using PCR applied to viral supernatants (Quinn &amp; Trevor, 1997; Morgan et al., 1990), hemagglutination assays, tissue culture infectious doses (TCID50) or egg infectious doses (EID50). An exemplary method of assessing viral titer is described in Section 6, below. 
     Incorporation of nucleotide sequences encoding a heterologous peptide or protein (e.g., a transgene into the genome of an oncolytic virus described herein, such as an APMV described herein, can be assessed by any method known in the art or described herein (e.g., in cell culture, an animal model or viral culture in embryonated eggs)). For example, viral particles from cell culture of the allantoic fluid of embryonated eggs can be purified by centrifugation through a sucrose cushion and subsequently analyzed for protein expression by Western blotting using methods well known in the art. 
     Immunofluorescence-based approaches may also be used to detect virus and assess viral growth. Such approaches are well known to those of skill in the art, e.g., fluorescence microscopy and flow cytometry (see, eg., Section 6, infra). Methods for flow cytometry, including fluorescence activated cell sorting (FACS), are available (see, e.g., Owens, et al. (1994)  Flow Cytometry Principles for Clinical Laboratory Practice , John Wiley and Sons, Hoboken, N.J.; Givan (2001)  Flow Cytometry,  2 nd    ed .; Wiley-Liss, Hoboken, N.J.; Shapiro (2003)  Practical Flow Cytometry , John Wiley and Sons, Hoboken, N.J.). Fluorescent reagents suitable for modifying nucleic acids, including nucleic acid primers and probes, polypeptides, and antibodies, for use, e.g., as diagnostic reagents, are available (Molecular Probesy (2003) Catalogue, Molecular Probes, Inc., Eugene, Oreg.; Sigma-Aldrich (2003)  Catalogue , St. Louis, Mo.). See, e.g., the assays described in Section 6, infra. 
     Standard methods of histology of the immune system are described (see, e.g., Muller-Harmelink (ed.) (1986)  Human Thymus: Histopathology and Pathology , Springer Verlag, New York, N.Y.; Hiatt, et al. (2000)  Color Atlas of Histology , Lippincott, Williams, and Wilkins, Phila, Pa.; Louis, et al. (2002)  Basic Histology: Text and Atlas , McGraw-Hill, New York, N.Y.). See also Section 6, infra, for histology and immunohistochemistry assays that may be used. 
     5.8.2 Interferon Assays 
     IFN induction by an oncolytic virus described herein, such as an APMV described herein, may be determined using techniques known to one of skill in the art. For example, the amount of IFN induced in cells following infection with an oncolytic virus described herein, such as an APMV described herein, may be determined using an immunoassay (e.g., an ELISA or Western blot assay) to measure IFN expression or to measure the expression of a protein whose expression is induced by IFN. Alternatively, the amount of IFN induced may be measured at the RNA level by assays, such as Northern blots and quantitative RT-PCR, known to one of skill in the art. In specific embodiments, the amount of IFN released may be measured using an ELISPOT assay. Further, the induction and release of cytokines and/or interferon-stimulated genes may be determined by, e.g., an immunoassay or ELISPOT assay at the protein level and/or quantitative RT-PCR or northern blots at the RNA level. 
     5.8.3 Activation Marker Assays and Immune Cell Infiltration Assay 
     The expression of a T cell marker, B cell marker, activation marker, co-stimulatory molecule, ligand, or inhibitory molecule by immune cells induced by an oncolytic virus described herein, such as an APMV described herein, may be assessed. Techniques for assessing the expression of T cell marker, B cell marker, activation marker, co-stimulatory molecule, ligand, or inhibitory molecule by immune cells are known to one of skill in the art. For example, the expression of T cell marker, B cell marker, an activation marker, co-stimulatory molecule, ligand, or inhibitory molecule by an immune cell can be assessed by flow cytometry. In a specific embodiment, a method described in Section 6, infra, is used to assess immune cell infiltration, activation or both. 
     5.8.4 Toxicity Studies 
     In some embodiments, an oncolytic virus described herein, such as an APMV described herein, or composition thereof, or a combination therapy described herein are tested for cytotoxicity in mammalian, preferably human, cell lines. In certain embodiments, cytotoxicity is assessed in one or more of the following non-limiting examples of cell lines: U937, a human monocyte cell line; primary peripheral blood mononuclear cells (PBMC); Huh7, a human hepatoblastoma cell line; HL60 cells, HT1080, HEK 293T and 293H, MLPC cells, human embryonic kidney cell lines; human melanoma cell lines, such as SkMe12, SkMe1-119 and SkMe1-197; THP-1, monocytic cells; a HeLa cell line; and neuroblastoma cells lines, such as MC-IXC, SK-N-MC, SK-N-MC, SK-N-DZ, SH-SY5Y, and BE(2)-C. In some embodiments, the ToxLite assay is used to assess cytotoxicity. 
     Many assays well-known in the art can be used to assess viability of cells or cell lines following infection with an oncolytic virus described herein, such as an APMV described herein, or composition thereof, and, thus, determine the cytotoxicity of the APMV or composition thereof. For example, cell proliferation can be assayed by measuring Bromodeoxyuridine (BrdU) incorporation, ( 3 H) thymidine incorporation, by direct cell count, or by detecting changes in transcription, translation or activity of known genes such as proto-oncogenes (e.g., fos, myc) or cell cycle markers (Rb, cdc2, cyclin A, D1, D2, D3, E, etc.). The levels of such protein and mRNA and activity can be determined by any method well known in the art. For example, protein can be quantitated by known immunodiagnostic methods such as ELISA, Western blotting or immunoprecipitation using antibodies, including commercially available antibodies. mRNA can be quantitated using methods that are well known and routine in the art, for example, using northern analysis, RNase protection, or polymerase chain reaction in connection with reverse transcription. Cell viability can be assessed by using trypan-blue staining or other cell death or viability markers known in the art. In a specific embodiment, the level of cellular ATP is measured to determined cell viability. In preferred embodiments, an APMV described herein or composition thereof does not kill healthy (i.e., non-cancerous) cells. 
     In specific embodiments, cell viability may be measured in three-day and seven-day periods using an assay standard in the art, such as the CellTiter-Glo Assay Kit (Promega) which measures levels of intracellular ATP. A reduction in cellular ATP is indicative of a cytotoxic effect. In another specific embodiment, cell viability can be measured in the neutral red uptake assay. In other embodiments, visual observation for morphological changes may include enlargement, granularity, cells with ragged edges, a filmy appearance, rounding, detachment from the surface of the well, or other changes. 
     The oncolytic viruses described herein, such as an APMVs described herein, or compositions thereof, or combination therapies can be tested for in vivo toxicity in animal models. For example, animal models, known in the art to test the effects of compounds on cancer can also be used to determine the in vivo toxicity of an oncolytic virus described herein, such as an APMV described herein, or a composition thereof, or combination therapies. For example, animals are administered a range of pfu of an oncolytic virus described herein, such as an APMV described herein, and subsequently, the animals are monitored over time for various parameters, such as one, two or more of the following: lethality, weight loss or failure to gain weight, and levels of serum markers that may be indicative of tissue damage (e.g., creatine phosphokinase level as an indicator of general tissue damage, level of glutamic oxalic acid transaminase or pyruvic acid transaminase as indicators for possible liver damage). These in vivo assays may also be adapted to test the toxicity of various administration mode and regimen in addition to dosages. 
     The toxicity, efficacy or both of an oncolytic virus described herein, such as an APMV described herein, or a composition thereof, or a combination therapy described herein can be determined by standard pharmaceutical procedures in cell cultures or experimental animals. In a specific embodiment, the cytotoxicity of an oncolytic virus described herein, such as an APMV described herein, is determined by methods set forth in Section 6, infra. 
     The data obtained from the cell culture assays and animal studies can be used in formulating a range of dosage of the therapies for use in subjects. 
     5.8.5 Biological Activity Assays 
     An oncolytic virus described herein, such as an APMV described herein, or a composition thereof, or a combination therapy described herein can be tested for biological activity using animal models for treating cancer. (see, e.g., Section 6). For example, an oncolytic virus described herein, such as an APMV described herein, or a composition thereof, and a VEGFR-3-activating agent described herein can be tested for biological activity using animal models for treating cancer. In another example, an oncolytic virus described herein, such as an APMV described herein, or a composition thereof, and a VEGF-C agent or a VEGF-D agent described herein can be tested for biological activity using animal models for treating cancer. Such animal model systems include, but are not limited to, rats, mice, hamsters, cotton rats, chicken, cows, monkeys (e.g., African green monkey), pigs, dogs, rabbits, etc. In a specific embodiment, an animal model such as described in Section 6, infra, is used to test the utility of an oncolytic virus described herein, such as an APMV described herein, or composition thereof to treat cancer. 
     5.8.6 Expression of Transgene 
     The expression of a protein in cells infected with a recombinant oncolytic virus, such as a recombinant APMV described herein, wherein the recombinant oncolytic virus comprises a packaged genome comprising a transgene encoding a heterologous protein, may be conducted using any assay known in the art, such as, e.g., western blot, immunofluorescence, flow cytometry, and ELISA, or any assay described herein (see, e.g., Section 6). In a specific embodiment, an assay described in Section 6, infra, is used to assess transgene expression. 
     In a specific aspect, an ELISA is utilized to detect expression of a heterologous protein encoded by a transgene in cells infected with a recombinant oncolytic virus, such as a recombinant APMV described herein, comprising a packaged genome comprising the transgene. 
     The expression of a transgene may also be measured at the RNA level by assays, such as Northern blots and quantitative RT-PCR, known to one of skill in the art. 
     In addition to expression of a transgene, the function of the protein encoded by the transgene may be assessed by techniques known to one of skill in the art. For example, one or more functions of a protein described herein or known to one of skill in the art may be assessed using techniques known to one of skill in the art. 
     5.9 Kits 
     In one aspect, provided herein is a pharmaceutical pack or kit comprising one or more containers filled with one or more of the ingredients of a composition (e.g., a pharmaceutical compositions) described herein. In a specific embodiment, provided herein is a pharmaceutical pack or kit comprising a container, wherein the container comprises an oncolytic virus described herein, such as an APMV (e.g., AMPV-1 or APMV-4), or a pharmaceutical composition comprising an oncolytic virus described herein, such as an APMV (e.g., AMPV-1 or APMV-4). In a particular embodiment, provided herein is a pharmaceutical pack or kit comprising a container, wherein the container comprises an APMV-1 described herein, or a pharmaceutical composition comprising an APMV-1 described herein. In another particular embodiment, provided herein is a pharmaceutical pack or kit comprising a container, wherein the container comprises an APMV-4 described herein, or a pharmaceutical composition comprising an APMV-4 described herein. In some embodiments, the pharmaceutical pack or kit comprises a second container, wherein the second container comprises a VEGFR-3-activating agent. In certain embodiments, the pharmaceutical pack or kit comprises a second container, wherein the second container comprises a VEGF-C agent. In some embodiments, the pharmaceutical pack or kit comprises a second container, wherein the second container comprises a VEGF-D agent. In certain embodiments, the pharmaceutical pack or kit comprises a second container, wherein the second container comprises a VEGF-C agent and a VEGF-D agent. In some embodiments, the pharmaceutical pack or kit comprises an additional container, wherein the second container comprises an additional prophylactic or therapeutic agent, such as, e.g., described in Section 5.7.2. Optionally associated with such container(s) can be a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals or biological products, which notice reflects approval by the agency of manufacture, use or sale for human administration. In a specific embodiment, the pharmaceutical pack or kit includes instructions for use of the oncolytic virus (e.g., APMV) or composition thereof and/or VEGFR-3-activating agent or composition thereof, VEGF-C agent or composition thereof or VEGF-D agent or composition thereof for the treatment of cancer. For example, the instructions may describe the methods for treating cancer described herein. 
     5.10 Sequences 
       
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Primer Sequences. 
               
            
           
           
               
               
               
            
               
                 Primer 
                   
                 SEQ 
               
               
                 name 
                 Sequence (5′-3′) 
                 ID NO. 
               
               
                   
               
               
                 mVEGFC-fwd 
                 ACCGAGTTCCCCCCCccgcgg TTAGAAAAAA T 
                 65 
               
               
                   
                 ACGGGTAGAA CCGCCACC ATG CAT CTG CTG TGT TTC 
                   
               
               
                   
                 CTG TC 
                   
               
               
                   
               
               
                 mVEGFC-rev 
                 TTGGACCTTGGGTCCgcggg CTA ATT CAG ATG AGG TCG 
                 66 
               
               
                   
                 CTT CCA GTA T 
                   
               
               
                   
               
               
                 APMV4- 
                 CCAAGCTTGCATGCC ACG AAA AAG AAG AAT AAA AGG 
                 67 
               
               
                 PCR1-1-F 
                 CA 
                   
               
               
                   
               
               
                 APMV4- 
                 GGG CGC GCC ACT GAG TCT T 
                 68 
               
               
                 PCR1-1-R 
                   
                   
               
               
                   
               
               
                 APMV4- 
                 CTC AGT GGC GCG CCC CA 
                 69 
               
               
                 PCR1-2-F 
                   
                   
               
               
                   
               
               
                 APMV4- 
                 GAT GTC GAC GGA CGG TGT G 
                 70 
               
               
                 PCR1-2-R 
                   
                   
               
               
                   
               
               
                 APMV4- 
                 CCG TCC GTC GAC ATC CCT 
                 71 
               
               
                 PCR1-3-F 
                   
                   
               
               
                   
               
               
                 APMV4- 
                 CGG TAC CCG GGG ATC CAT CAC CTG CAG GAT TAC AT 
                 72 
               
               
                 PCR1-3-R 
                   
                   
               
               
                   
               
               
                 APMV4- 
                 CCAAGCTTGCATGCC taatcctgcaggtgatgaatctg 
                 73 
               
               
                 PCR2-1-F 
                   
                   
               
               
                   
               
               
                 APMV4- 
                 GTT CGA TCG TTT TTA ATT AAA AAG G 
                 74 
               
               
                 PCR2-1-R 
                   
                   
               
               
                   
               
               
                 APMV4- 
                 TAA AAA CGA TCG AAC TGA GG 
                 75 
               
               
                 PCR2-2-F 
                   
                   
               
               
                   
               
               
                 APMV4- 
                 CGG TAC CCG GGG ATC ATT TTA CGG CCG CTC AGG G 
                 76 
               
               
                 PCR2-2-R 
                   
                   
               
               
                   
               
               
                 APMV4- 
                 CCAAGCTTGCATGCC GAG CGG CCG TAA AAT TAA CAC 
                 53 
               
               
                 PCR3-F 
                   
                   
               
               
                   
               
               
                 APMV4-125-R 
                 GAT TAT CTA GAT TGT CAG AAC CCA TAA AGA ATT TGG 
                 54 
               
               
                   
               
               
                 APMV4-125-F 
                 ACA ATC TAG ATA ATC TTG ATA TCT ACC AGC AGC 
                 55 
               
               
                   
               
               
                 APMV4- 
                 CGG TAC CCG GGG ATC AAG AAA TAA AAG ACA TAT TTT 
                 56 
               
               
                 PCR3-R 
                 TTA TTA AAT ATT AAT ACG 
                   
               
               
                   
               
               
                 InF-N- 
                 CACGATAATACCATGGCTGGTGTCTTCTCCCAGTATG 
                 57 
               
               
                 APMV4-F 
                   
                   
               
               
                   
               
               
                 InF-N- 
                 TTAGGCCTCTCGAGCCTGCAGCTACAGTTCAAAGTCGGGTT 
                 58 
               
               
                 APMV4-R 
                 GATAGTC 
                   
               
               
                   
               
               
                 InF-P- 
                 CACGATAATACCATGGATTTTACTGACATTGATGCTGTCAA 
                 59 
               
               
                 APMV4-F 
                 CTC 
                   
               
               
                   
               
               
                 InF-P- 
                 TTAGGCCTCTCGAGCCTGCAGCTAGAGCCCAAGGGCTTGT 
                 60 
               
               
                 APMV4-R 
                 C 
                   
               
               
                   
               
               
                 InF-L- 
                 CACGATAATACCATGTCCAATCAGGCAGCTGAGATTATAC 
                 61 
               
               
                 APMV4-F 
                   
                   
               
               
                   
               
               
                 InF-L- 
                 TTAGGCCTCTCGAGCCTGCAGCTAAAGTGAGAGGTAGCCC 
                 62 
               
               
                 APMV4-R 
                 CAACC 
                   
               
               
                   
               
               
                 APMV- 
                 cacaccgtccgtcga C ATT TTT AAT TAA AAT AGG GTG GGG 
                 63 
               
               
                 mVEGFC-fwd 
                   
                   
               
               
                   
               
               
                 APMV- 
                 GGC AAG GGA TGT CGA CCC GGT CAG TTC AG 
                 64 
               
               
                 mVEGFC-rev 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 APMV SEQUENCES 
               
            
           
           
               
               
               
            
               
                   
                   
                 SEQ 
               
               
                   
                   
                 ID 
               
               
                 Description 
                 Sequence 
                 NO. 
               
               
                   
               
               
                 Avian 
                 GCGAAAAAGAAGAATAAAAGGCAGAAGCCTTTTAAAAGGAACCCTGGG 
                 77 
               
               
                 paramyxovirus 
                 CTGTCGTAGGTGTGGGAAGGTTGTATTCCGAGTGCGCCTCCGAGGCATC 
                   
               
               
                 4 strain 
                 TACTCTACACCTATCACAATGGCTGGTGTCTTCTCCCAGTATGAGAGGTT 
                   
               
               
                 APMV4/mall 
                 TGTGGACAATCAATCCCAAGTATCAAGGAAGGATCATCGGTCCCTGGCA 
                   
               
               
                 ard/Belgium/ 
                 GGGGGATGCCTTAAAGTCAACATCCCTATGCTTGTCACTGCATCTGAAG 
                   
               
               
                 15129/07 
                 ATCCCACCACTCGTTGGCAACTAGCATGTTTATCTCTAAGGCTCTTGATC 
                   
               
               
                 complete 
                 TCCAACTCATCAACCAGTGCTATCCGACAGGGGGCAATACTGACTCTCA 
                   
               
               
                 genome 
                 TGTCACTACCGTCACAAAATATGAGAGCAACGGCAGCTATTGCTGGTTC 
                   
               
               
                 Genbank: 
                 CACAAATGCAGCTGTTATCAACACTATGGAAGTCTTGAGTGTCAATGAC 
                   
               
               
                 JN571485.1 
                 TGGACCCCATCCTTCGACCCTAGGAGCGGTCTCTCTGAAGAGGATGCTC 
                   
               
               
                   
                 AGGTTTTCAGAGACATGGCAAGGGACCTGCCCCCTCAGTTCACCTCCGG 
                   
               
               
                   
                 ATCACCCTTTACATCAGCATTGGCGGAGGGGTTTACCCCAGAAGACACC 
                   
               
               
                   
                 CACGACCTAATGGAGGCCTTGACCAGTGTGCTGATACAGATCTGGATCC 
                   
               
               
                   
                 TGGTGGCTAAGGCCATGACCAACATTGATGGCTCTGGGGAGGCCAATG 
                   
               
               
                   
                 AGAGACGTCTTGCAAAGTACATCCAAAAGGGACAGCTTAATCGCCAGTT 
                   
               
               
                   
                 TGCAATTGGTAATCCTGCTCGTCTGATAATCCAACAGACGATCAAAAGC 
                   
               
               
                   
                 TCCTTAACTGTCCGCAGGTTCTTGGTCTCTGAGCTTCGTGCATCACGAGG 
                   
               
               
                   
                 TGCAGTGAAAGAAGGATCCCCTTACTATGCAGCTGTTGGGGATATCCAC 
                   
               
               
                   
                 GCTTACATCTTTAACGCAGGACTGACACCATTCTTGACTACCTTAAGAT 
                   
               
               
                   
                 ATGGGATAGGCACCAAGTATGCTGCTGTTGCACTCAGTGTGTTCGCTGC 
                   
               
               
                   
                 AGACATTGCAAAATTAAAGAGCCTACTTACCCTGTACCAAGACAAGGGT 
                   
               
               
                   
                 GTGGAGGCCGGATACATGGCACTCCTTGAAGATCCAGATTCCATGCACT 
                   
               
               
                   
                 TTGCACCCGGAAATTTCCCACACATGTACTCCTATGCGATGGGGGTGGC 
                   
               
               
                   
                 TTCTTACCATGACCCCAGCATGCGCCAATACCAATATGCCAGGAGGTTC 
                   
               
               
                   
                 CTCAGCCGTCCCTTCTACTTGCTAGGGAGGGACATGGCCGCCAAGAACA 
                   
               
               
                   
                 CAGGCACGCTGGATGAGCAACTGGCAAAGGAACTGCAAGTGTCAGAAA 
                   
               
               
                   
                 GAGACCGCGCCGCATTGTCCGCTGCGATTCAATCAGCAATGGAGGGGG 
                   
               
               
                   
                 GAGAATCTGACGACTTCCCACTGTCGGGATCCATGCCGGCTCTCTCCGA 
                   
               
               
                   
                 CACTGCGCAACCAGTTACCCCAAGAACCCAACAGTCCCAGCTTTCCCCT 
                   
               
               
                   
                 CCACAATCATCAAGCATGTCTCAATCAGCGCCCAGGACCCCGGACTACC 
                   
               
               
                   
                 AGCCTGATTTTGAACTGTAGGCTGCATCCACGCACCAACAACAGGCAAA 
                   
               
               
                   
                 AGAAATCACCCTCCTCCCCACACATCCCACCCACTCACCCGCCGAGATC 
                   
               
               
                   
                 CAATCCAACACCCCAGCATCCCCATCATTTAATTAAAAACTGACCAATA 
                   
               
               
                   
                 GGGTGGGGAAGGAGAGTTATTGGCTGTTGCCAAGTTTGTGCAGCAATGG 
                   
               
               
                   
                 ATTTCACCGACATTGATGCTGTCAACTCATTAATTGAATCATCATCAGCA 
                   
               
               
                   
                 ATCATAGATTCCATACAGCATGGAGGGCTGCAACCATCGGGCACTGTCG 
                   
               
               
                   
                 GCCTATCGCAAATCCCAAAGGGGATAACCAGCGCTTTAACTAAGGCCTG 
                   
               
               
                   
                 GGAGGCTGAGGCAGCAACTGCTGGCAATGGGGACACCCAACACAAACC 
                   
               
               
                   
                 TGACAGTCCGGAGGATCATCAGGCCAACGACACAGACTCCCCCGAAGA 
                   
               
               
                   
                 CACAGGCACCAACCAGACCATCCAGGAAGCCAATATCGTTGAAACACC 
                   
               
               
                   
                 CCACCCCGAAGTGCTATCGGCAGCCAAAGCCAGACTCAAGAGGCCCAA 
                   
               
               
                   
                 GGCAGGGAGGGACACCCACGACAATCCCTCTGCGCAACCTGATCATTTT 
                   
               
               
                   
                 TTAAAGGGGGGCCCCCTGAGCCCACAACCAGCGGCACCATGGGTGCAA 
                   
               
               
                   
                 AGTCCACCCATTCATGGAGGTCCCGGCACCGTCGATCCCCGCCCATCAC 
                   
               
               
                   
                 AAACTCAGGATCATTCCCTCACCGGAGAGAAATGGCAATCGTCACCGAC 
                   
               
               
                   
                 AAAGCAACCGGAGACATTGAACTGGTGGAATGGTGCAACCCGGGGTGC 
                   
               
               
                   
                 ACCGCAATCCGAACTGAACCAACCAGACTCGACTGTGTATGCGGACACT 
                   
               
               
                   
                 GCCCCACCATCTGCAGCCTCTGCATGTATGACGACTGATCAGGTACAAC 
                   
               
               
                   
                 TATTAATGAAGGAGGTTGCCGATATGAAATCACTCCTTCAGGCATTAGT 
                   
               
               
                   
                 AAAGAACCTAGCTGTCCTGCCTCAACTAAGGAACGAGGTTGCAGCAATC 
                   
               
               
                   
                 AGGACATCACAGGCCATGATAGAGGGGACACTCAATTCAATCAAGATT 
                   
               
               
                   
                 CTCGATCCTGGGAATTATCAAGAATCATCACTAAACAGCTGGTTCAAAC 
                   
               
               
                   
                 CACGCCAAGATCACGCGGTTGTTGTGTCCGGACCAGGGAATCCATTGAC 
                   
               
               
                   
                 CATGCCAACCCCAATCCAAGACAACACCATATTCCTGGATGAACTGGCA 
                   
               
               
                   
                 AGACCTCATCCTAGTTTGGTCAATCCGTCCCCGCCCACTACCAACACTA 
                   
               
               
                   
                 ATGTTGATCTTGGCCCACAGAAGCAGGCTGCGATAGCTTATATCTCAGC 
                   
               
               
                   
                 AAAATGCAAGGATCCAGGGAAACGAGATCAGCTCTCAAAGCTCATCGA 
                   
               
               
                   
                 GCGAGCAACCACCTTGAGCGAGATCAACAAAGTCAAAAGACAGGCCCT 
                   
               
               
                   
                 CGGCCTCTAGATCACTCGACCACCCCCAGTAATGAATACAACAATAATC 
                   
               
               
                   
                 AGAACCCCCCTAAAACACATGGTCAACCCAACACACCACCCGCACCAC 
                   
               
               
                   
                 CCGCTACTATCCTTTGCCAGAAACTCCGCCGCAGCCGATTTATTCAAAA 
                   
               
               
                   
                 GAAGCCATTTGATATGACTTAGCAACCGCAAGATAGGGTGGGGAAGGT 
                   
               
               
                   
                 GCTTTGCCTGCAAGAGGGCTCCCTCATCTTCAGACACGTACCCGCCAAC 
                   
               
               
                   
                 CCACCAGTGACGCAATGGCAGACATGGACACCGTATATATCAATCTGAT 
                   
               
               
                   
                 GGCAGATGATCCAACCCACCAAAAAGAACTGCTGTCCTTTCCCCTCGTT 
                   
               
               
                   
                 CCCGTGACTGGTCCTGACGGGAAAAAGGAACTCCAACACCAGGTCCGG 
                   
               
               
                   
                 ACTCAATCCTTGCTCGCCTCAGACAAGCAAACTGAGAGGTTCATCTTCC 
                   
               
               
                   
                 TCAACACTTACGGGTTTATCTATGACACTACACCGGACAAGACAACTTT 
                   
               
               
                   
                 TTCCACCCCAGAGCACATCAATCAGCCCAAGAGAACGATGGTGAGTGCT 
                   
               
               
                   
                 GCGATGATGACCATTGGCCTGGTCCCCGCCAATATACCCTTGAACGAAT 
                   
               
               
                   
                 TAACAGCTACTGTGTTCGGCCTGAAAGTAAGAGTGAGGAAGAGTGCGA 
                   
               
               
                   
                 GATATCGAGAGGTGGTCTGGTATCAGTGCAATCCTGTACCAGCCCTGCT 
                   
               
               
                   
                 TGCAGCCACCAGGTTCGGTCGCCAAGGAGGTCTCGAATCAAGCACTGG 
                   
               
               
                   
                 AGTCAGCGTAAAGGCCCCCGAGAAGATAGATTGCGAGAAGGATTATAC 
                   
               
               
                   
                 TTACTACCCTTATTTCCTATCTGTGTGCTACATCGCCACTTCCAACCTGTT 
                   
               
               
                   
                 CAAGGTACCAAAAATGGTTGCTAATGCGACCAACAGTCAATTATACCAC 
                   
               
               
                   
                 CTGACTATGCAGGTCACATTTGCCTTTCCAAAAAACATCCCCCCAGCTA 
                   
               
               
                   
                 ACCAGAAACTTCTGACACAAGTGGATGAAGGATTCGAGGGCACTGTGG 
                   
               
               
                   
                 ACTGCCATTTTGGGAACATGCTGAAAAAGGATCGGAAAGGGAATATGA 
                   
               
               
                   
                 GGACATTGTCGCAGGCGGCAGACAAGGTCAGACGGATGAATATCCTTG 
                   
               
               
                   
                 TTGGTATCTTTGACTTGCATGGGCCGACACTCTTCCTGGAGTATACTGGG 
                   
               
               
                   
                 AAACTAACAAAAGCTCTGTTAGGGTTCATGTCTACTAGCCGAACAGCAA 
                   
               
               
                   
                 TCATCCCCATATCTCAGCTCAATCCTATGCTGGGTCAACTTATGTGGAGC 
                   
               
               
                   
                 AGTGATGCCCAGATAGTAAAATTAAGAGTGGTCATAACTACATCCAAAC 
                   
               
               
                   
                 GCGGCCCATGCGGGGGTGAGCAGGAGTATGTGCTGGATCCCAAATTCA 
                   
               
               
                   
                 CAGTTAAAAAAGAGAAAGCCCGACTCAACCCTTTCAAGAAGGCAGCCC 
                   
               
               
                   
                 AATGATCAAATCTGCAGGATCTCAAGAATCAGACCACTCTATACTATTC 
                   
               
               
                   
                 ACCGATCAATAGACATGTAACTATACAGTTGATGGACCTATGAAGAATC 
                   
               
               
                   
                 AATTAGCAAACCGAATCCTTACTAGGGTGGGGAAGGAGTTGATTGGGT 
                   
               
               
                   
                 GTCTAAACAAAAGCATTCCTTTACACCTCCTCGCTACGAAACAACCATA 
                   
               
               
                   
                 ATGAGGTTATCACGCACAATCCTGACTTTGATTCTCAGCACACTTACCG 
                   
               
               
                   
                 GCTATTTAATGAATGCCCACTCCACCAATGTGAATGAGAAACCAAAGTC 
                   
               
               
                   
                 TGAGGGGATTAGGGGGGATCTTATACCAGGCGCAGGTATTTTTGTAACT 
                   
               
               
                   
                 CAAGTCCGACAACTACAGATCTACCAACAGTCTGGGTATCATGACCTTG 
                   
               
               
                   
                 TCATCAGGTTATTACCTCTTCTACCGGCAGAACTTAATGATTGTCAAAG 
                   
               
               
                   
                 GGAAGTTGTCACAGAGTACAACAACACGGTATCACAGCTGTTGCAGCCT 
                   
               
               
                   
                 ATCAAAACCAACCTGGATACCTTATTGGCTGATGGTAGCACAAGGGATG 
                   
               
               
                   
                 CCGATATACAGCCACGGTTCATTGGGGCAATAATAGCCACAGGTGCCCT 
                   
               
               
                   
                 GGCGGTGGCTACGGTAGCTGAGGTGACTGCAGCCCAAGCACTATCTCAG 
                   
               
               
                   
                 TCGAAAACAAACGCTCAAAATATTCTCAAGTTGAGAGATAGTATTCAGG 
                   
               
               
                   
                 CTACCAACCAAGCAGTTTTCGAAATTTCACAAGGACTCGAGGCAACTGC 
                   
               
               
                   
                 AACTGTGCTATCAAAACTGCAAACTGAGCTCAATGAGAACATTATCCCA 
                   
               
               
                   
                 AGCCTGAACAACTTGTCCTGTGCTGCCATGGGGAATCGCCTTGGTGTAT 
                   
               
               
                   
                 CACTATCACTCTACTTGACCTTAATGACCACTCTATTTGGGGACCAGATC 
                   
               
               
                   
                 ACAAACCCAGTGCTGACACCAATCTCCTATAGCACTCTATCGGCAATGG 
                   
               
               
                   
                 CAGGCGGTCACATTGGCCCGGTGATGAGTAAAATATTAGCTGGATCTGT 
                   
               
               
                   
                 CACAAGTCAGTTGGGGGCAGAACAGTTGATTGCTAGCGGCTTAATACAG 
                   
               
               
                   
                 TCACAGGTAGTAGGTTATGATTCCCAATATCAATTATTGGTTATCAGGG 
                   
               
               
                   
                 TCAACCTTGTACGGATTCAAGAGGTCCAGAATACGAGGGTCGTATCACT 
                   
               
               
                   
                 AAGAACACTAGCGGTCAATAGGGATGGTGGACTTTATAGAGCCCAGGT 
                   
               
               
                   
                 GCCTCCCGAGGTAGTTGAACGGTCTGGCATTGCAGAGCGATTTTATGCA 
                   
               
               
                   
                 GATGATTGTGTTCTTACTACAACTGATTACATTTGCTCATCGATCCGATC 
                   
               
               
                   
                 TTCTCGGCTTAATCCAGAGTTAGTCAAGTGTCTCAGTGGTGCACTTGATT 
                   
               
               
                   
                 CATGCACATTTGAGAGGGAAAGTGCATTATTGTCGACCCCTTTCTTTGTA 
                   
               
               
                   
                 TACAACAAGGCAGTCGTCGCAAATTGTAAAGCAGCAACATGTAGATGT 
                   
               
               
                   
                 AATAAACCGCCATCTATTATTGCCCAATACTCTGCATCAGCTCTAGTCAC 
                   
               
               
                   
                 CATCACCACCGACACCTGTGCCGACCTTGAAATTGAGGGTTATCGCTTC 
                   
               
               
                   
                 AACATACAGACTGAATCCAACTCATGGGTTGCACCAAACTTCACGGTCT 
                   
               
               
                   
                 CGACTTCACAGATTGTATCAGTTGATCCAATAGACATCTCCTCTGACATT 
                   
               
               
                   
                 GCCAAAATCAACAGTTCCATCGAGGCTGCGAGAGAGCAGCTGGAACTG 
                   
               
               
                   
                 AGCAACCAGATCCTTTCCCGGATCAACCCACGAATTGTGAATGATGAAT 
                   
               
               
                   
                 CACTGATAGCTATTATCGTGACAATTGTTGTGCTTAGTCTCCTTGTAATC 
                   
               
               
                   
                 GGTCTGATTGTTGTTCTCGGTGTGATGTATAAGAATCTTAAGAAAGTCC 
                   
               
               
                   
                 AACGAGCTCAAGCTGCCATGATGATGCAGCAAATGAGCTCATCACAGC 
                   
               
               
                   
                 CTGTGACCACTAAATTAGGGACGCCTTTCTAGGAGAATAATCATATCAC 
                   
               
               
                   
                 TCTACTCAATGATGAGCAAAACGTACCAATCGTCAATGATTGTGTCACG 
                   
               
               
                   
                 AGGCCGGTTGGGAATGCATCGAATCTCTCCCCTTTCTTTTTAATTAAAAA 
                   
               
               
                   
                 CATTTGAAGTGAGGGTGAGAGGGGGGGAGTGTATGGTAGGGTGGGGAA 
                   
               
               
                   
                 GGTAGCCAATTCCTGCCTATTGGGCCGACCGTATCAAAAGAACTCAACA 
                   
               
               
                   
                 GAAGTCTAGATACAGGGTGACATGGAGGGCAGCCGTGATAATCTTACA 
                   
               
               
                   
                 GTGGATGATGAATTAAAGACAACATGGAGGTTAGCTTATAGAGTTGTGT 
                   
               
               
                   
                 CCCTTCTATTGATGGTGAGCGCTTTGATAATCTCTATAGTAATCCTGACA 
                   
               
               
                   
                 AGAGATAACAGCCAAAGCATAATCACAGCGATCAACCAGTCATCCGAC 
                   
               
               
                   
                 GCAGACTCAAAGTGGCAAACGGGAATAGAAGGGAAAATCACCTCCATT 
                   
               
               
                   
                 ATGACTGATACGCTCGATACCAGGAATGCAGCCCTTCTCCACATTCCAC 
                   
               
               
                   
                 TCCAGCTCAACACGCTTGAGGCGAACCTTTTGTCCGCCCTTGGGGGCAA 
                   
               
               
                   
                 CACAGGAATTGGTCCCGGGGATCTAGATCACTGCCGTTACCCTGTTCAT 
                   
               
               
                   
                 GACTCCGCTTACCTGCATGGAGTTAATCGATTACTCATCAACCAGACAG 
                   
               
               
                   
                 CTGATTACACAGCAGAAGGCCCCCTAGATCATGTGAACTTTATTCCAGC 
                   
               
               
                   
                 CCCGGTTACGACCACTGGATGCACAAGGATACCATCCTTTTCCGTGTCA 
                   
               
               
                   
                 TCGTCCATTTGGTGCTATACACACAACGTGATCGAAACCGGTTGCAATG 
                   
               
               
                   
                 ACCACTCAGGTAGTAACCAATATATCAGCATGGGAGTCATTAAGAGAG 
                   
               
               
                   
                 CGGGCAACGGCCTACCTTACTTCTCGACAGTTGTAAGTAAATATCTGAC 
                   
               
               
                   
                 TGATGGGTTGAATAGGAAAAGCTGTTCTGTAGCCGCCGGATCCGGGCAT 
                   
               
               
                   
                 TGCTACCTCCTTTGCAGCTTAGTGTCGGAACCCGAACCTGATGACTATGT 
                   
               
               
                   
                 GTCACCTGATCCCACACCGATGAGGTTAGGGGTGCTAACGTGGGATGGG 
                   
               
               
                   
                 TCTTACACTGAACAGGTGGTACCCGAAAGAATATTCAAGAACATATGGA 
                   
               
               
                   
                 GTGCAAACTACCCAGGAGTAGGGTCAGGTGCTATAGTAGGGAATAAGG 
                   
               
               
                   
                 TGTTATTCCCATTTTACGGCGGAGTGAGAAATGGATCGACCCCGGAGGT 
                   
               
               
                   
                 GATGAATAGGGGAAGATACTACTACATCCAGGATCCAAATGACTATTGT 
                   
               
               
                   
                 CCTGACCCGCTACAAGATCAGATCTTAAGGGCGGAACAATCGTATTACC 
                   
               
               
                   
                 CAACTCGATTTGGTAGGAGGATGGTAATGCAAGGGGTCCTAGCATGTCC 
                   
               
               
                   
                 AGTATCCAACAATTCAACAATAGCAAGCCAATGTCAATCTTACTATTTT 
                   
               
               
                   
                 AATAACTCATTAGGATTCATTGGGGCAGAATCTAGAATCTATTACCTCA 
                   
               
               
                   
                 ATGGTAACATTTACCTTTATCAGAGAAGCTCGAGCTGGTGGCCTCATCC 
                   
               
               
                   
                 CCAGATTTACCTGCTTGATTCCAGGATTGCAAGTCCGGGTACTCAGAAC 
                   
               
               
                   
                 ATTGACTCAGGTGTTAATCTCAAGATGTTAAATGTTACTGTGATTACAC 
                   
               
               
                   
                 GACCATCATCTGGTTTTTGTAATAGTCAGTCACGATGCCCTAATGACTGC 
                   
               
               
                   
                 TTATTCGGGGTCTACTCGGATATCTGGCCTCTTAGCCTTACCTCAGATAG 
                   
               
               
                   
                 CATATTCGCGTTCACAATGTATTTACAGGGGAAGACAACACGTATTGAC 
                   
               
               
                   
                 CCGGCTTGGGCACTATTCTCCAATCATGCGATTGGGCATGAGGCTCGTC 
                   
               
               
                   
                 TGTTCAATAAGRAGGTTAGTGCTGCTTATTCTACCACCACTTGTTTTTCG 
                   
               
               
                   
                 GACACTATCCAAAATCAGGTGTATTGCCTGAGTATACTTGAGGTCAGGA 
                   
               
               
                   
                 GTGAGCTCTTGGGAGCATTCAAAATAGTACCATTCCTCTATCGCGTCTTG 
                   
               
               
                   
                 TAGGCATCCATTCAGCCAAAAAACTTGAGTGACCATGAGGTTAACACCT 
                   
               
               
                   
                 GATCCCCTTCAAAAACATCTATCTTAATTACCGTTCTAGATCCATGATTA 
                   
               
               
                   
                 GGTACCTTTCCAATCAATCATTTGGTTTTTAATTAAAAACGAAAGAATG 
                   
               
               
                   
                 GGCCTAGTTCCAAGAAAGGGCTGGAACCCATTAGGGTGGGGAAGGATT 
                   
               
               
                   
                 GCTTTGCTCCTTGACTCACACCTGCGTACACTCGATCTCACTTCTATAAA 
                   
               
               
                   
                 GAAGGAATCCTTCTCAAATTCGCCCCACAATGTCCAATCAGGCAGCTGA 
                   
               
               
                   
                 GATTATACTACCCACCTTCCATCTAGAATCACCCTTAATCGAGAATAAG 
                   
               
               
                   
                 TGCTTCTATTATATGCAATTACTTGGTCTCGTGTTGCCACATGATCACTG 
                   
               
               
                   
                 GAGATGGAGGGCATTCGTTAACTTTACAGTGGATCAGGTGCACCTTAAA 
                   
               
               
                   
                 AATCGTAATCCCCGCTTAATGGCCCACATCGACCACACTAAAGATAGAT 
                   
               
               
                   
                 TAAGGACTCATGGTGTCTTAGGTTTCCACCAGACTCAGACAAGTATGAG 
                   
               
               
                   
                 CCGTTACCGTGTTTTGCTTCATCCTGAAACCTTACCTTGGCTATCAGCCA 
                   
               
               
                   
                 TGGGAGGATGCATCAATCAGGTTCCTAAAGCATGGCGGAACACTCTGA 
                   
               
               
                   
                 AATCGATCGAGCACAGTGTAAAGCAGGAGGCACCTCAACTAAAGTTAC 
                   
               
               
                   
                 TCATGGAGAGAACCTCATTAAAATTAACTGGAGTACCTTACTTGTTCTCT 
                   
               
               
                   
                 AATTGCAATCCCGGGAAAACCACAGCAGGAACTATGCCTGTCCTAAGTG 
                   
               
               
                   
                 AGATGGCATCGGAACTCTTATCAAATCCTATCTCCCAATTCCAATCAAC 
                   
               
               
                   
                 ATGGGGGTGTGCTGCTTCGGGGTGGCACCATGTAGTCAGTATCATGAGG 
                   
               
               
                   
                 CTCCAACAATATCAAAGAAGGACAGGTAAGGAAGAGAAAGCAATCACT 
                   
               
               
                   
                 GAAGTTCAGTATGGCACGGACACCTGTCTCATTAACGCAGACTACACCG 
                   
               
               
                   
                 TTGTTTTTTCCACACAGAACCGTGTTATAACGGTCTTGCCTTTCGATGTT 
                   
               
               
                   
                 GTCCTCATGATGCAAGACCTGCTAGAATCCCGACGGAATGTCCTGTTCT 
                   
               
               
                   
                 GTGCCCGCTTTATGTATCCCAGAAGCCAACTTCATGAGAGGATAAGTAC 
                   
               
               
                   
                 AATATTAGCCCTTGGAGACCAACTGGGGAGAAAAGCACCCCAAGTCCT 
                   
               
               
                   
                 GTATGATTTTGTAGCAACCCTTGAGTCATTTGCATACGCAGCTGTTCAAC 
                   
               
               
                   
                 TTCATGACAACAATCCTACCTACGGTGGGGCCTTCTTTGAATTCAATATC 
                   
               
               
                   
                 CAAGAGTTAGAATCTATTCTGTCCCCTGCACTTAGTAAGGATCAGGTCA 
                   
               
               
                   
                 ACTTCTACATAGGTCAAGTTTGCTCAGCGTACAGTAACCTTCCTCCATCT 
                   
               
               
                   
                 GAATCGGCAGAATTGCTGTGCCTGCTACGCCTGTGGGGTCATCCCTTGC 
                   
               
               
                   
                 TAAACAGCCTTGATGCAGCAAAGAAAGTCAGGGAATCTATGTGTGCCG 
                   
               
               
                   
                 GGAAGGTTCTCGATTACAACGCCATTCGACTCGTCTTGTCTTTTTATCAT 
                   
               
               
                   
                 ACGTTACTAATCAATGGGTATCGGAAGAAGCACAAGGGTCGCTGGCCA 
                   
               
               
                   
                 AATGTGAATCAACATTCACTCCTCAACCCGATAGTGAGGCAGCTTTATT 
                   
               
               
                   
                 TTGATCAGGAGGAGATCCCACACTCTGTTGCCCTTGAGCACTATTTGGA 
                   
               
               
                   
                 TGTCTCAATGATAGAATTTGAGAAAACTTTTGAAGTGGAACTATCTGAC 
                   
               
               
                   
                 AGCCTAAGCATCTTCCTGAAGGATAAGTCGATAGCTTTGGACAAGCAAG 
                   
               
               
                   
                 AATGGTACAGTGGTTTTGTCTCAGAAGTGACTCCGAAGCACCTGCGAAT 
                   
               
               
                   
                 GTCCCGTCATGATCGCAAGTCTACCAATAGGCTCCTGTTAGCCTTCATTA 
                   
               
               
                   
                 ACTCCCCTGAATTCGATGTTAAGGAAGAGCTTAAATACTTGACTACGGG 
                   
               
               
                   
                 TGAGTACGCTACTGACCCAAATTTCAATGTCTCTTACTCACTCAAAGAG 
                   
               
               
                   
                 AAGGAAGTAAAGAAAGAAGGGCGCATTTTCGCAAAAATGTCACAAAAG 
                   
               
               
                   
                 ATGAGAGCATGCCAGGTTATTTGTGAAGAATTGCTAGCACATCATGTGG 
                   
               
               
                   
                 CTCCTTTGTTTAAAGAGAATGGTGTTACTCAATCGGAGCTATCCCTGAC 
                   
               
               
                   
                 AAAAAATTTGTTGGCTATTAGCCAACTGAGTTACAACTCGATGGCCGCT 
                   
               
               
                   
                 AAGGTGCGATTGCTGAGGCCAGGGGACAAGTTCACTGCTGCACACTATA 
                   
               
               
                   
                 TGACCACAGACCTAAAGAAGTACTGTCTCAATTGGCGGCACCAGTCAGT 
                   
               
               
                   
                 CAAACTGTTCGCCAGAAGCCTGGATCGACTGTTTGGGCTAGACCATGCT 
                   
               
               
                   
                 TTTTCTTGGATACATGTCCGTCTCACCAACAGCACTATGTACGTTGCTGA 
                   
               
               
                   
                 CCCCTTCAATCCACCAGACTCAGATGCATGCACAAACTTAGACGACAAT 
                   
               
               
                   
                 AAGAACACCGGGATTTTTATTATAAGTGCACGAGGTGGTATAGAAGGCC 
                   
               
               
                   
                 TCCAACAAAAACTATGGACTGGCATATCAATCGCAATTGCCCAAGCAGC 
                   
               
               
                   
                 AGCAGCCCTCGAAGGCTTACGAATTGCTGCTACTCTGCAGGGGGATAAC 
                   
               
               
                   
                 CAAGTTTTGGCGATTACAAAGGAGTTCATGACCCCAGTCCCGGAGGATG 
                   
               
               
                   
                 TAATCCATGAGCAGCTATCTGAGGCGATGTCCCGATACAAAAGGACTTT 
                   
               
               
                   
                 CACATACCTCAATTATTTAATGGGGCATCAGTTGAAGGATAAGGAAACC 
                   
               
               
                   
                 ATCCAATCCAGTGATTTCTTTGTGTACTCCAAAAGAATCTTCTTCAATGG 
                   
               
               
                   
                 ATCAATCTTAAGTCAATGCCTCAAGAACTTCAGTAAACTCACTACTAAT 
                   
               
               
                   
                 GCCACTACCCTTGCTGAGAACACTGTGGCCGGCTGCAGTGACATCTCTT 
                   
               
               
                   
                 CATGCATTGCCCGTTGTGTGGAAAACGGGTTGCCTAAGGATGCCGCATA 
                   
               
               
                   
                 TATTCAGAATATAATCATGACTCGGCTTCAACTATTGCTAGATCATTACT 
                   
               
               
                   
                 ATTCAATGCATGGCGGCATAAACTCAGAATTAGAGCAGCCAACTTTAAG 
                   
               
               
                   
                 TATCTCTGTTCGAAACGCGACCTACTTACCATCTCAACTAGGCGGTTAC 
                   
               
               
                   
                 AATCATTTGAATATGACCCGACTATTCTGCCGCAATATCGGCGACCCGC 
                   
               
               
                   
                 TTACCAGTTCTTGGGCGGAGTCAAAAAGACTAATGGATGTTGGCCTTCT 
                   
               
               
                   
                 CAGTCGTAAGTTCTTAGAGGGGATATTATGGAGACCCCCGGGAAGTGG 
                   
               
               
                   
                 GACATTTTCAACACTCATGCTTGATCCGTTCGCACTTAACATTGATTACC 
                   
               
               
                   
                 TGAGGCCGCCAGAGACAATTATCCGAAAACACACCCAAAAAGTCTTGTT 
                   
               
               
                   
                 GCAAGATTGCCCAAATCCCCTATTAGCAGGTGTCGTTGACCCGAACTAC 
                   
               
               
                   
                 AACCAAGAATTAGAGCTATTAGCTCAGTTCTTGCTTGATCGGGAAACCG 
                   
               
               
                   
                 TTATCCCCAGGGCTGCCCATGCCATCTTTGAATTGTCTGTCTTGGGAAGG 
                   
               
               
                   
                 AAAAAACATATACAAGGATTGGTAGATACTACAAAAACAATTATTCAG 
                   
               
               
                   
                 TGCTCATTGGAAAGACAGCCATTGTCCTGGAGGAAAGTTGAGAACATTG 
                   
               
               
                   
                 TTACCTACAACGCGCAGTATTTCCTCGGGGCCACCCAACAGGCTGATAC 
                   
               
               
                   
                 TAATGTCTCAGAAGGGCAGTGGGTGATGCCAGGTAACTTCAAGAAGCTT 
                   
               
               
                   
                 GTGTCCCTTGACGATTGCTCAGTCACGTTGTCCACTGTATCGCGGCGCAT 
                   
               
               
                   
                 ATCGTGGGCCAATCTACTGAACTGGAGAGCTATAGATGGTTTAGAAACC 
                   
               
               
                   
                 CCGGATGTGATAGAGAGTATTGATGGCCGCCTTGTACAATCATCCAATC 
                   
               
               
                   
                 AATGTGGCCTATGTAATCAAGGGTTGGGATCCTACTCCTGGTTCTTCTTG 
                   
               
               
                   
                 CCCTCTGGGTGTGTGTTCGACCGTCCACAAGATTCTCGGGTAGTTCCAA 
                   
               
               
                   
                 AGATGCCATACGTGGGGTCCAAAACAGATGAGAGACAGACTGCATCAG 
                   
               
               
                   
                 TGCAAGCTATACAGGGATCCACTTGTCACCTCAGAGCAGCATTGAGGCT 
                   
               
               
                   
                 TGTATCACTCTATCTATGGGCCTATGGAGATTCTGACATATCATGGCTAG 
                   
               
               
                   
                 AAGCTGCGACACTGGCTCAAACACGGTGCAATGTTTCTCTTGATGACTT 
                   
               
               
                   
                 GCGAATCTTGAGCCCTCTCCCTTCTTCGGCGAATTTACACCACAGATTAA 
                   
               
               
                   
                 ATGACGGGGTAACACAGGTTAAATTCATGCCCGCCACATCGAGCCGAGT 
                   
               
               
                   
                 GTCAAAGTTCGTCCAAATTTGCAATGACAACCAGAATCTTATCCGTGAT 
                   
               
               
                   
                 GATGGGAGTGTTGATTCCAATATGATTTATCAACAAGTTATGATATTGG 
                   
               
               
                   
                 GGCTTGGAGAGATTGAATGCTTGCTAGCTGACCCAATCGATACAAACCC 
                   
               
               
                   
                 AGAACAATTGATTCTTCATCTACACTCTGATAATTCTTGCTGTCTCCGGG 
                   
               
               
                   
                 AGATGCCAACGACCGGCTTTGTACCTGCTCTAGGACTAACCCCATGTTT 
                   
               
               
                   
                 AACTGTCCCAAAGCACAATCCTTACATTTATGATGATAGCCCAATACCC 
                   
               
               
                   
                 GGTGATTTGGACCAGAGGCTCATCCAGACCAAATTTTTCATGGGTTCTG 
                   
               
               
                   
                 ACAATTTGGATAATCTTGATATCTACCAACAGCGGGCTTTATTGAGTAG 
                   
               
               
                   
                 GTGTGTGGCTTATGATGTTATCCAATCGATATTTGCTTGTGATGCACCAG 
                   
               
               
                   
                 TCTCTCAGAAGAATGACGCAATCCTTCACACTGACTATCATGAGAATTG 
                   
               
               
                   
                 GATCTCAGAGTTCCGATGGGGTGACCCTCGTATTATCCAAGTAACGGCA 
                   
               
               
                   
                 GGCTACGAGTTAATTCTGTTCCTTGCATACCAGCTTTATTATCTCAGAGT 
                   
               
               
                   
                 GAGGGGTGACCGTGCAATCCTATGTTATATTGACAGGATACTCAACAGG 
                   
               
               
                   
                 ATGGTATCTTCCAATCTAGGCAGTCTCATCCAGACACTCTCTCATCCAGA 
                   
               
               
                   
                 GATTAGGAGGAGATTCTCATTGAGTGATCAAGGGTTCCTTGTTGAAAGG 
                   
               
               
                   
                 GAGCTAGAGCCAGGTAAGCCCTTGGTTAAACAAGCGGTTATGTTCTTGA 
                   
               
               
                   
                 GGGACTCGGTCCGCTGCGCTTTAGCAACTATCAAGGCAGGAATTGAGCC 
                   
               
               
                   
                 TGAGATCTCCCGAGGTGGCTGTACTCAGGATGAGCTGAGCTTTACTCTT 
                   
               
               
                   
                 AAGCACTTACTGTGTCGGCGTCTCTGTGTAATCGCTCTCATGCATTCAGA 
                   
               
               
                   
                 AGCAAAGAACTTGGTTAAAGTTAGAAACCTTCCTGTAGAAGAGAAAAC 
                   
               
               
                   
                 CGCCTTACTGTACCAGATGTTGGTCACTGAGGCCAATGCTAGGAAATCA 
                   
               
               
                   
                 GGATCTGCTAGCATCATCATAAATCTAGTCTCGGCACCCCAGTGGGACA 
                   
               
               
                   
                 TTCATACACCAGCATTGTATTTTGTATCAAAGAAAATGCTAGGGATGCT 
                   
               
               
                   
                 TAAAAGGTCAACCACACCCTTGGATATAAGTGACCTCTCCGAGAGCCAG 
                   
               
               
                   
                 AATCCCGCACTTGCAGAGCTGAATGATGTTCCCGGTCACATGGCAGAAG 
                   
               
               
                   
                 AATTTCCCTGTTTGTTTAGTAGTTATAACGCCACATATGAAGACACAATT 
                   
               
               
                   
                 ACTTACAATCCAATGACTGAAAAACTCGCCTTACACTTGGACAACAGTT 
                   
               
               
                   
                 CCACCCCATCCAGAGCACTTGGTCGTCACTACATCCTGCGGCCTCTTGG 
                   
               
               
                   
                 GCTCTACTCATCCGCATGGTACCGGTCTGCAGCACTACTAGCGTCAGGG 
                   
               
               
                   
                 GCCCTAAATGGGTTGCCTGAGGGGTCGAGCCTGTACCTAGGAGAAGGG 
                   
               
               
                   
                 TACGGGACCACCATGACTCTGCTTGAGCCCGTTGTCAAGTCTTCAACTG 
                   
               
               
                   
                 TTTACTACCATACATTGTTTGACCCAACCCGGAATCCTTCACAGCGGAA 
                   
               
               
                   
                 CTATAAACCAGAACCACGGGTATTCACGGATTCTATTTGGTACAAGGAT 
                   
               
               
                   
                 GATTTCACACGGCCACCTGGTGGTATTATCAATCTGTGGGGTGAAGATA 
                   
               
               
                   
                 TACGTCAGAGTGATATCACACAGAAAGACACGGTCAACTTCATACTATC 
                   
               
               
                   
                 TCAGATCCCGCCAAAATCACTTAAGTTGATACACGTTGATATTGAGTTC 
                   
               
               
                   
                 TCACCAGACTCCGATGTACGGACACTACTATCTGGCTATTCTCATTGTGC 
                   
               
               
                   
                 ACTATTGGCCTACTGGCTATTGCAACCTGGAGGGCGATTTGCAGTTAGA 
                   
               
               
                   
                 GTTTTCTTAAGTGACCATATCATAGTAAACTTGGTCACTGCAATCCTGTC 
                   
               
               
                   
                 TGCTTTTGACTCTAATCTGGTGTGCATTGCATCAGGATTGACACACAAG 
                   
               
               
                   
                 GATGATGGGGCAGGTTATATTTGCGCAAAAAAGCTTGCAAATGTTGAGG 
                   
               
               
                   
                 CTTCAAGGATCGAGTACTACTTGAGGATGGTCCATGGTTGTGTTGACTC 
                   
               
               
                   
                 ATTAAAGATCCCTCATCAATTAGGAATCATTAAATGGGCCGAGGGCGAG 
                   
               
               
                   
                 GTGTCCCAACTTACCAGAAAGGCGGATGATGAAATAAATTGGCGGTTA 
                   
               
               
                   
                 GGTGATCCAGTTACCAGATCATTTGATCCAGTTTCTGAGCTAATAATTGC 
                   
               
               
                   
                 ACGAACAGGGGGGTCTGTATTAATGGAATACGGGGCTTTTACTAACCTC 
                   
               
               
                   
                 AGGTGTGCGAACTTGGCAGATACATACAAACTTCTGGCTTCAATTGTAG 
                   
               
               
                   
                 AGACCACCCTAATGGAAATAAGGGTTGAGCAAGATCAATTAGAAGATA 
                   
               
               
                   
                 ATTCGAGGAGACAAATCCAAGTAGTTCCCGCTTTCAACACTAGATCTGG 
                   
               
               
                   
                 GGGAAGGATCCGTACGCTGATTGAGTGTGCTCAGCTGCAGATTATAGAT 
                   
               
               
                   
                 GTTATTTGTGTAAACATAGATCACCTCTTTCCTAAACACCGACATGTTCT 
                   
               
               
                   
                 TGTCACACAACTTACCTACCAGTCAGTGTGCCTTGGGGACTTGATTGAA 
                   
               
               
                   
                 GGCCCCCAAATTAAGACGTATCTAAGGGCCAGGAAGTGGATCCAACGT 
                   
               
               
                   
                 CAGGGACTCAATGAGACAGTTAACCATATCATCACTGGACAAGTGTCGC 
                   
               
               
                   
                 GGAATAAAGCAAGGGATTTTTTCAAGAGGCGTCTGAAGTTGGTTGGCTT 
                   
               
               
                   
                 TTCACTCTGCGGTGGTTGGAGCTACCTCTCACTTTAGCTGTTCAGGTTGT 
                   
               
               
                   
                 TGATTATTATGAATAATCGGAGTCGGAATCGTAAATAGGAAGTCACAAA 
                   
               
               
                   
                 GTTGTGAATAAACAATGATTGCATTAGTATTTAATAAAAAATATGTCTT 
                   
               
               
                   
                 TTATTTCGT 
                   
               
               
                 Avian 
                 ACGAAAAAGAAGAATAAAAGGCAGAAGCCTTTTAAAAGGAACCCTGGG 
                 78 
               
               
                 paramyxovirus 
                 CTGTCGTAGGTGTGGGAAGGTTGTATTCCGAGTGCGCCTCCGAGGCATC 
                   
               
               
                 4 APMV- 
                 TACTCTACACCTATCACAATGGCTGGTGTCTTCTCCCAGTATGAGAGGTT 
                   
               
               
                 4/duck/Hong 
                 TGTGGACAATCAATCCCAAGTGTCAAGGAAGGATCATCGGTCCTTAGCA 
                   
               
               
                 kong/D3/75, 
                 GGAGGATGCCTTAAAGTTAACATCCCTATGCTTGTCACTGCATCTGAAG 
                   
               
               
                 complete 
                 ACCCCACCACTCGTTGGCAACTAGCATGCTTATCTCTAAGGCTCCTGATC 
                   
               
               
                 genome 
                 TCCAACTCATCAACCAGTGCTATCCGTCAGGGGGCAATACTGACTCTCA 
                   
               
               
                 Genbank: 
                 TGTCATTACCATCACAAAACATGAGAGCAACAGCAGCTATTGCTGGTTC 
                   
               
               
                 FJ177514.1 
                 CACAAATGCAGCTGTTATCAACACCATGGAAGTCTTAAGTGTCAACGAC 
                   
               
               
                   
                 TGGACCCCATCCTTCGACCCTAGGAGCGGTCTTTCTGAGGAAGATGCTC 
                   
               
               
                   
                 AAGTTTTCAGAGACATGGCAAGAGATCTGCCCCCTCAGTTCACCTCTGG 
                   
               
               
                   
                 ATCACCCTTCACATCAGCATTGGCGGAGGGGTTCACTCCTGAAGATACT 
                   
               
               
                   
                 CATGACCTGATGGAGGCCTTGACCAGTGTGCTGATACAGATCTGGATCC 
                   
               
               
                   
                 TGGTGGCTAAGGCCATGACCAACATTGACGGCTCTGGGGAGGCCAATG 
                   
               
               
                   
                 AAAGACGTCTTGCAAAGTACATCCAAAAAGGACAGCTTAATCGTCAGTT 
                   
               
               
                   
                 TGCAATTGGTAATCCTGCCCGTCTGATAATCCAACAGACAATCAAAAGC 
                   
               
               
                   
                 TCCTTAACTGTCCGTAGGTTCTTGGTCTCTGAGCTTCGTGCGTCACGAGG 
                   
               
               
                   
                 TGCAGTAAAAGAAGGATCCCCTTACTATGCAGCTGTTGGGGATATCCAC 
                   
               
               
                   
                 GCTTACATCTTTAATGCGGGATTGACACCATTCTTGACCACCTTAAGATA 
                   
               
               
                   
                 CGGGATAGGCACCAAGTACGCCGCTGTTGCACTCAGTGTGTTCGCTGCA 
                   
               
               
                   
                 GATATTGCAAAGTTGAAGAGCCTACTTACCCTGTACCAGGACAAGGGTG 
                   
               
               
                   
                 TAGAAGCTGGATACATGGCACTCCTTGAGGATCCAGACTCCATGCACTT 
                   
               
               
                   
                 TGCACCTGGAAACTTCCCACACATGTACTCCTATGCAATGGGGGTAGCT 
                   
               
               
                   
                 TCTTACCATGATCCTAGCATGCGCCAATACCAATACGCCAGGAGGTTCC 
                   
               
               
                   
                 TCAGCCGTCCTTTCTACTTACTAGGAAGGGACATGGCCGCCAAGAACAC 
                   
               
               
                   
                 AGGCACGCTGGATGAGCAACTGGCGAAGGAACTGCAAGTATCAGAGAG 
                   
               
               
                   
                 AGATCGCGCCGCATTATCCGCTGCGATTCAATCAGCGATGGAGGGGGG 
                   
               
               
                   
                 AGAGTCCGACGACTTCCCACTGTCGGGATCCATGCCGGCTCTCTCTGAG 
                   
               
               
                   
                 AATGCGCAACCAGTTACCCCCAGACCTCAACAGTCCCAGCTCTCTCCCC 
                   
               
               
                   
                 CCCAATCATCAAACATGCCCCAATCAGCACCCAGGACCCCAGACTATCA 
                   
               
               
                   
                 ACCCGACTTTGAACTGTAGGCTTCATCACCGCACCAACAACAGCCCAAG 
                   
               
               
                   
                 AAGACCACCCCTCCCCCCACACATCTCACCCAGCCACCCATAAAGACTC 
                   
               
               
                   
                 AGTCCCACGCCCCAGCATCTCCTTCATTTAATTAAAAACCGACCAACAG 
                   
               
               
                   
                 GGTGGGGAAGGAGAGTCATTGGCTACTGCCAATTGTGTGCAGCAATGG 
                   
               
               
                   
                 ATTTTACTGACATTGATGCTGTCAACTCATTGATCGAATCATCATCGGCA 
                   
               
               
                   
                 ATCATAGACTCCATACAGCATGGAGGGCTGCAACCAGCGGGCACCGTC 
                   
               
               
                   
                 GGCCTATCGCAGATCCCAAAAGGGATAACCAGCGCATTAACCAAGGCC 
                   
               
               
                   
                 TGGGAGGCTGAGGCGGCAACTGCCGGTAATGGGGACACCCAACACAAA 
                   
               
               
                   
                 TCTGACAGTCCGGAGGATCATCAGGCCAACGACACAGATTCCCCTGAAG 
                   
               
               
                   
                 ACACAGGTACTGACCAGACCACCCAGGAGGCCAACATCGTTGAGACAC 
                   
               
               
                   
                 CCCACCCCGAGGTGCTGTCAGCAGCCAAAGCCAGACTCAAGAGGCCCA 
                   
               
               
                   
                 AAGCAGGGAGGGACACCCGCGACAACTCCCCTGCGCAACCCGATCATC 
                   
               
               
                   
                 TTTTAAAGGGGGGCCTCCTGAGCCCACAACCAGCAGCATCATGGGTGCA 
                   
               
               
                   
                 AAATCCACCCAGTCATGGAGGTCCCGGCACCGCCGATCCCCGCCCATCA 
                   
               
               
                   
                 CAAACTCAGGATCATTCCCCCACCGGAGAGAAATGGCGATTGTCACCGA 
                   
               
               
                   
                 CAAAGCAACCGGAGACATTGAACTGGTGGAGTGGTGCAACCCGGGGTG 
                   
               
               
                   
                 CACAGCAGTCCGAATTGAACCCACCAGACTCGACTGTGTATGCGGACAC 
                   
               
               
                   
                 TGCCCCACCATCTGTAGCCTCTGCATGTATGACGACTGATCAGGTACAA 
                   
               
               
                   
                 CTACTAATGAAGGAGGTTGCTGACATAAAATCACTCCTTCAGGCGTTAG 
                   
               
               
                   
                 TGAGGAACCTCGCTGTCTTGCCCCAATTGAGGAATGAGGTTGCAGCAAT 
                   
               
               
                   
                 CAGAACATCACAGGCCATGATAGAGGGGACACTCAATTCGATCAAGAT 
                   
               
               
                   
                 TCTTGACCCTGGGAATTATCAGGAATCATCACTAAACAGTTGGTTCAAA 
                   
               
               
                   
                 CCTCGCCAAGATCACACTGTTGTTGTGTCTGGACCAGGGAATCCATTGG 
                   
               
               
                   
                 CCATGCCAACCCCAGTCCAAGACAACACCATATTCCTGGACGAGCTAGC 
                   
               
               
                   
                 CAGACCTCATCCTAGTGTGGTCAATCCTTCCCCACCCATCACCAACACC 
                   
               
               
                   
                 AATGTTGACCTTGGCCCACAGAAGCAGGCTGCAATAGCCTATATCTCCG 
                   
               
               
                   
                 CTAAATGCAAGGATCCGGGGAAACGAGATCAGCTATCAAGGCTCATTG 
                   
               
               
                   
                 AGCGAGCAACCACCCCAAGTGAGATCAACAAAGTTAAAAGACAAGCCC 
                   
               
               
                   
                 TTGGGCTCTAGATCACTCGATCACCCCTCATGGTGATCACAACAATAAT 
                   
               
               
                   
                 CAGAACCCTTCCGAACCACATGACCAACCCAGCCCACCGCCCACACCGT 
                   
               
               
                   
                 CCATCGACATCCCTTGCCAAACATCCTGCCGTAGCTGATTTATTCAAAA 
                   
               
               
                   
                 GAGCTCATTTGATATGACCTGGTAATCATAAAATAGGGTGGGGAAGGTG 
                   
               
               
                   
                 CTTTGCCTGTAAGGGGGCTCCCTCATCTTCAGACACGTGCCCGCCATCTC 
                   
               
               
                   
                 ACCAACAGTGCAATGGCAGACATGGACACGGTGTATATCAATCTGATG 
                   
               
               
                   
                 GCAGATGACCCAACCCACCAAAAAGAACTGCTGTCCTTTCCTCTCATCC 
                   
               
               
                   
                 CTGTGACCGGTCCTGACGGGAAGAAGGAACTCCAACACCAGATCCGGA 
                   
               
               
                   
                 CCCAATCCTTGCTCGCCTCAGACAAACAAACTGAACGGTTCATCTTCCT 
                   
               
               
                   
                 CAACACTTACGGATTCATCTATGACACCACACCGGACAAGACAACTTTT 
                   
               
               
                   
                 TCCACCCCAGAGCATATTAATCAGCCTAAGAGGACGACGGTGAGTGCC 
                   
               
               
                   
                 GCGATGATGACCATTGGCCTGGTTCCCGCCAATATACCCCTGAACGAAC 
                   
               
               
                   
                 TAACGGCTACTGTGTTCAGCCTTAAAGTAAGAGTGAGGAAAAGTGCGA 
                   
               
               
                   
                 GGTATCGGGAAGTGGTCTGGTATCAATGCAATCCAGTACCGGCCCTGCT 
                   
               
               
                   
                 TGCAGCCACCAGGTTTGGTCGCCAAGGAGGTCTCGAGTCGAGCACTGGA 
                   
               
               
                   
                 GTCAGTGTAAAGGCTCCCGAGAAGATAGATTGTGAGAAGGATTATACCT 
                   
               
               
                   
                 ACTACCCTTATTTCTTATCTGTGTGCTACATCGCCACCTCCAACCTGTTC 
                   
               
               
                   
                 AAGGTACCGAGGATGGTTGCTAATGCAACCAACAGTCAATTATACCACC 
                   
               
               
                   
                 TTACCATGCAGGTCACATTTGCCTTTCCAAAAAACATCCCTCCAGCCAA 
                   
               
               
                   
                 CCAGAAACTCCTGACACAGGTGGATGAGGGATTCGAGGGCACTGTGGA 
                   
               
               
                   
                 TTGCCATTTTGGGAACATGCTGAAAAAGGATCGGAAAGGGAACATGAG 
                   
               
               
                   
                 GACACTGTCCCAGGCGGCAGATAAGGTCAGACGAATGAATATTCTTGTT 
                   
               
               
                   
                 GGTATCTTTGACTTGCATGGGCCAACGCTCTTCCTGGAGTATACCGGGA 
                   
               
               
                   
                 AACTGACAAAGGCTCTGCTAGGGTTCATGTCCACCAGCCGAACAGCAAT 
                   
               
               
                   
                 CATCCCCATATCTCAGCTCAATCCCATGCTGAGTCAACTCATGTGGAGC 
                   
               
               
                   
                 AGTGATGCCCAGATAGTAAAGTTAAGGGTTGTCATAACTACATCCAAAC 
                   
               
               
                   
                 GCGGCCCGTGCGGGGGTGAGCAGGAGTATGTGCTGGATCCCAAATTCA 
                   
               
               
                   
                 CAGTTAAGAAAGAAAAGGCTCGACTCAACCCTTTCGAGAAGGCAGCCT 
                   
               
               
                   
                 AATGATTTAATCCGCAAGATCCCAGAAATCAGACCACTCTATACTATCC 
                   
               
               
                   
                 ACTGATCACTGGAAATGTAATTGTACAGTTGATGAATCTGTGAAGAATC 
                   
               
               
                   
                 AATTAAAAAACCGGATCCTTATTAGGGTGGGGAAGTAGTTGATTGGGTG 
                   
               
               
                   
                 TCTAAACAAAAGCATTTCTTCACACCTCCCCGCCACGAAACAACCACAA 
                   
               
               
                   
                 TGAGGCTATCAAACACAATCTTGACCTTGATTCTCATCATACTTACCGGC 
                   
               
               
                   
                 TATTTGATAGGTGTCCACTCCACCGATGTGAATGAGAAACCAAAGTCCG 
                   
               
               
                   
                 AAGGGATTAGGGGTGATCTTACACCAGGTGCGGGTATTTTCGTAACTCA 
                   
               
               
                   
                 AGTCCGACAGCTCCAGATCTACCAACAGTCTGGGTACCATGATCTTGTC 
                   
               
               
                   
                 ATCAGATTGTTACCTCTTCTACCAACAGAGCTTAATGATTGTCAAAGGG 
                   
               
               
                   
                 AAGTTGTCACAGAGTACAATAACACTGTATCACAGCTGTTGCAGCCTAT 
                   
               
               
                   
                 CAAAACCAACCTGGATACTTTGTTGGCAGATGGTAGCACAAGGGATGTT 
                   
               
               
                   
                 GATATACAGCCGCGATTCATTGGGGCAATAATAGCCACAGGTGCCCTGG 
                   
               
               
                   
                 CTGTAGCAACGGTAGCTGAGGTAACTGCAGCTCAAGCACTATCTCAGTC 
                   
               
               
                   
                 AAAAACGAATGCTCAAAATATTCTCAAGTTGAGAGATAGTATTCAGGCC 
                   
               
               
                   
                 ACCAACCAAGCAGTTTTTGAAATTTCACAGGGACTCGAAGCAACTGCAA 
                   
               
               
                   
                 CCGTGCTATCAAAACTGCAAACTGAGCTCAATGAGAATATCATCCCAAG 
                   
               
               
                   
                 TCTGAACAACTTGTCCTGTGCTGCCATGGGGAATCGCCTTGGTGTATCA 
                   
               
               
                   
                 CTCTCACTCTATTTGACCTTAATGACCACTCTATTTGGGGACCAGATCAC 
                   
               
               
                   
                 AAACCCAGTGCTGACGCCAATCTCTTACAGCACCCTATCGGCAATGGCG 
                   
               
               
                   
                 GGTGGTCACATTGGTCCAGTGATGAGTAAGATATTAGCCGGATCTGTCA 
                   
               
               
                   
                 CAAGTCAGTTGGGGGCAGAACAACTGATTGCTAGTGGCTTAATACAGTC 
                   
               
               
                   
                 ACAGGTAGTAGGTTATGATTCCCAGTATCAGCTGTTGGTTATCAGGGTC 
                   
               
               
                   
                 AACCTTGTACGGATTCAGGAAGTCCAGAATACTAGGGTTGTATCACTAA 
                   
               
               
                   
                 GAACACTAGCAGTCAATAGGGATGGTGGACTTTACAGAGCCCAGGTGC 
                   
               
               
                   
                 CACCCGAGGTAGTTGAGCGATCTGGCATTGCAGAGCGGTTTTATGCAGA 
                   
               
               
                   
                 TGATTGTGTTCTAACTACAACTGATTACATCTGCTCATCGATCCGATCTT 
                   
               
               
                   
                 CTCGGCTTAATCCAGAGTTAGTCAAGTGTCTCAGTGGGGCACTTGATTC 
                   
               
               
                   
                 ATGCACATTTGAGAGGGAAAGTGCATTACTGTCAACTCCCTTCTTTGTAT 
                   
               
               
                   
                 ACAACAAGGCAGTCGTCGCAAATTGTAAAGCAGCGACATGTAGATGTA 
                   
               
               
                   
                 ATAAACCGCCATCTATCATTGCCCAATACTCTGCATCAGCTCTAGTAAC 
                   
               
               
                   
                 CATCACCACCGACACTTGTGCTGACCTTGAAATTGAGGGTTATCGTTTC 
                   
               
               
                   
                 AACATACAGACTGAATCCAACTCATGGGTTGCACCAAACTTCACGGTCT 
                   
               
               
                   
                 CAACCTCACAAATAGTATCGGTTGATCCAATAGACATATCCTCTGACAT 
                   
               
               
                   
                 TGCCAAAATTAACAATTCTATCGAGGCTGCGCGAGAGCAGCTGGAACTG 
                   
               
               
                   
                 AGCAACCAGATCCTTTCCCGAATCAACCCACGGATTGTGAACGACGAAT 
                   
               
               
                   
                 CACTAATAGCTATTATCGTGACAATTGTTGTGCTTAGTCTCCTTGTAATT 
                   
               
               
                   
                 GGTCTTATTATTGTTCTCGGTGTGATGTACAAGAATCTTAAGAAAGTCC 
                   
               
               
                   
                 AACGAGCTCAAGCTGCTATGATGATGCAGCAAATGAGCTCATCACAGCC 
                   
               
               
                   
                 TGTGACCACCAAATTGGGGACACCCTTCTAGGTGAATAATCATATCAAT 
                   
               
               
                   
                 CCATTCAATAATGAGCGGGACATACCAATCACCAACGACTGTGTCACAA 
                   
               
               
                   
                 GGCCGGTTAGGAATGCACCGGATCTCTCTCCTTCCTTTTTAATTAAAAAC 
                   
               
               
                   
                 GGTTGAACTGAGGGTGAGGGGGGGGGTGTGCATGGTAGGGTGGGGAAG 
                   
               
               
                   
                 GTAGCCAATTCCTGCCCATTGGGCCGACCGTACCAAGAGAAGTCAACAG 
                   
               
               
                   
                 AAGTATAGATGCAGGGCGACATGGAGGGTAGCCGTGATAACCTCACAG 
                   
               
               
                   
                 TAGATGATGAATTAAAGACAACATGGAGGTTAGCTTATAGAGTTGTATC 
                   
               
               
                   
                 CCTCCTATTGATGGTGAGTGCCTTGATAATCTCTATAGTAATCCTGACGA 
                   
               
               
                   
                 GAGATAACAGCCAAAGCATAATCACGGCGATCAACCAGTCGTATGACG 
                   
               
               
                   
                 CAGACTCAAAGTGGCAAACAGGGATAGAAGGGAAAATCACCTCAATCA 
                   
               
               
                   
                 TGACTGATACGCTCGATACCAGGAATGCAGCTCTTCTCCACATTCCACT 
                   
               
               
                   
                 CCAGCTCAATACACTTGAGGCAAACCTGTTGTCCGCCCTCGGAGGTTAC 
                   
               
               
                   
                 ACGGGAATTGGCCCCGGAGATCTAGAGCACTGTCGTTATCCGGTTCATG 
                   
               
               
                   
                 ACTCCGCTTACCTGCATGGAGTCAATCGATTACTCATCAATCAAACAGC 
                   
               
               
                   
                 TGACTACACAGCAGAAGGCCCCCTGGATCATGTGAACTTCATTCCGGCA 
                   
               
               
                   
                 CCAGTTACGACTACTGGATGCACAAGGATCCCATCCTTTTCTGTATCATC 
                   
               
               
                   
                 ATCCATTTGGTGCTATACACACAATGTGATTGAAACAGGTTGCAATGAC 
                   
               
               
                   
                 CACTCAGGTAGTAATCAATATATCAGTATGGGGGTGATTAAGAGGGCTG 
                   
               
               
                   
                 GCAACGGCTTACCTTACTTCTCAACAGTCGTGAGTAAGTATCTGACCGA 
                   
               
               
                   
                 TGGGTTGAATAGAAAAAGCTGTTCCGTAGCTGCGGGATCCGGGCATTGT 
                   
               
               
                   
                 TACCTCCTTTGTAGCCTAGTGTCAGAGCCCGAACCTGATGACTATGTGTC 
                   
               
               
                   
                 ACCAGATCCCACACCGATGAGGTTAGGGGTGCTAACAAGGGATGGGTC 
                   
               
               
                   
                 TTACACTGAACAGGTGGTACCCGAAAGAATATTTAAGAACATATGGAG 
                   
               
               
                   
                 CGCAAACTACCCTGGGGTAGGGTCAGGTGCTATAGCAGGAAATAAGGT 
                   
               
               
                   
                 GTTATTCCCATTTTACGGCGGAGTGAAGAATGGATCAACCCCTGAGGTG 
                   
               
               
                   
                 ATGAATAGGGGAAGATATTACTACATCCAGGATCCAAATGACTATTGCC 
                   
               
               
                   
                 CTGACCCGCTGCAAGATCAGATCTTAAGGGCAGAACAATCGTATTATCC 
                   
               
               
                   
                 TACTCGATTTGGTAGGAGGATGGTAATGCAGGGAGTCCTAACATGTCCA 
                   
               
               
                   
                 GTATCCAACAATTCAACAATAGCCAGCCAATGCCAATCTTACTATTTCA 
                   
               
               
                   
                 ACAACTCATTAGGATTCATCGGGGCGGAATCTAGGATCTATTACCTCAA 
                   
               
               
                   
                 TGGTAACATTTACCTTTATCAAAGAAGCTCGAGCTGGTGGCCTCACCCC 
                   
               
               
                   
                 CAAATTTACCTACTTGATTCCAGGATTGCAAGTCCGGGTACGCAGAACA 
                   
               
               
                   
                 TTGACTCAGGCGTTAACCTCAAGATGTTAAATGTTACTGTCATTACACG 
                   
               
               
                   
                 ACCATCATCTGGCTTTTGTAATAGTCAGTCAAGATGCCCTAATGACTGCT 
                   
               
               
                   
                 TATTCGGGGTTTATTCAGATGTCTGGCCTCTTAGCCTTACCTCAGACAGC 
                   
               
               
                   
                 ATATTTGCATTTACAATGTACTTACAAGGGAAGACGACACGTATTGACC 
                   
               
               
                   
                 CAGCTTGGGCGCTATTCTCCAATCATGTAATTGGGCATGAGGCTCGTTT 
                   
               
               
                   
                 GTTCAACAAGGAGGTTAGTGCTGCTTATTCTACCACCACTTGTTTTTCGG 
                   
               
               
                   
                 ACACCATCCAAAACCAGGTGTATTGTCTGAGTATACTTGAAGTCAGAAG 
                   
               
               
                   
                 TGAGCTCTTGGGGGCATTCAAGATAGTGCCATTCCTCTATCGTGTCTTAT 
                   
               
               
                   
                 AGGCACCTGCTTGGTCAAGAACCCTGAGCAGCCATAAAATTAACACTTG 
                   
               
               
                   
                 ATCTTCCTTAAAAACACCTATCTAAATTACTGTCTGAGATCCCTGATTAG 
                   
               
               
                   
                 TTACCCTTTCAATCAATCAATTAATTTTTAATTAAAAACGGAAAAATGG 
                   
               
               
                   
                 GCCTAGTTCCAAGGAAAGGATGGGACCCATTAGGGTGGGGAAGGATTA 
                   
               
               
                   
                 CTTTGTTCCTTGACTCGCACCCACGTACACCCAATCCCATTCCTGTCAAG 
                   
               
               
                   
                 AAGGAACCCTTCCCAAACTCACCTTGCAATGTCCAATCAGGCAGCTGAG 
                   
               
               
                   
                 ATTATACTACCCACCTTCCATCTTTTATCACCCTTGATCGAGAATAAGTG 
                   
               
               
                   
                 CTTCTACTACATGCAATTACTTGGTCTCGTGTTACCACATGATCACTGGA 
                   
               
               
                   
                 GATGGAGGGCATTCGTCAATTTTACAGTGGATCAAGCACACCTTAAAAA 
                   
               
               
                   
                 TCGTAATCCCCGCTTAATGGCCCACATCGATCACACTAAGGATAGACTA 
                   
               
               
                   
                 AGGGCTCATGGTGTCTTGGGTTTCCACCAGACTCAGACAAGTGAGAGCC 
                   
               
               
                   
                 GTTTCCGTGTCTTGCTCCATCCTGAAACTTTACCTTGGCTATCAGCAATG 
                   
               
               
                   
                 GGAGGATGCATCAACCAGGTTCCCAAGGCATGGCGGAACACTCTGAAA 
                   
               
               
                   
                 TCTATCGAGCACAGTGTGAAGCAGGAGGCGACTCAACTGAAGTTACTCA 
                   
               
               
                   
                 TGGAAAAAACCTCACTAAAGCTAACAGGAGTATCTTACTTATTCTCCAA 
                   
               
               
                   
                 TTGCAATCCCGGGAAAACTGCAGCGGGAACTATGCCCGTACTAAGTGA 
                   
               
               
                   
                 GATGGCATCAGAACTCTTGTCAAATCCCATCTCCCAATTCCAATCAACA 
                   
               
               
                   
                 TGGGGGTGTGCTGCTTCAGGGTGGCACCATGTAGTCAGCATCATGAGGC 
                   
               
               
                   
                 TCCAACAGTATCAAAGAAGGACAGGTAAGGAAGAGAAAGCAATCACTG 
                   
               
               
                   
                 AAGTTCAGTATGGCTCGGACACCTGTCTCATTAATGCAGACTACACCGT 
                   
               
               
                   
                 CGTTTTTTCCGCACAGGACCGTGTCATAGCAGTCTTGCCTTTCGATGTTG 
                   
               
               
                   
                 TCCTCATGATGCAAGACCTGCTTGAATCCCGACGGAATGTCTTGTTCTGT 
                   
               
               
                   
                 GCCCGCTTTATGTATCCCAGAAGCCAACTACATGAGAGGATAAGTACAA 
                   
               
               
                   
                 TACTGGCCCTTGGAGACCAACTCGGGAGAAAAGCACCCCAAGTCCTGTA 
                   
               
               
                   
                 TGATTTCGTAGCTACCCTCGAATCATTTGCATACGCTGCTGTCCAACTTC 
                   
               
               
                   
                 ATGACAACAACCCTATCTACGGTGGGGCTTTCTTTGAGTTCAATATCCA 
                   
               
               
                   
                 AGAACTGGAAGCTATTTTGTCCCCTGCACTTAATAAGGATCAAGTCAAC 
                   
               
               
                   
                 TTCTACATAAGTCAAGTTGTCTCAGCATACAGTAACCTTCCCCCATCTGA 
                   
               
               
                   
                 ATCAGCAGAATTGCTATGCTTACTACGCCTGTGGGGTCATCCCTTGCTA 
                   
               
               
                   
                 AACAGTCTTGATGCAGCAAAGAAAGTCAGAGAATCTATGTGTGCTGGG 
                   
               
               
                   
                 AAGGTTCTTGATTATAATGCTATTCGACTAGTTTTGTCTTTTTATCATAC 
                   
               
               
                   
                 GTTATTAATCAATGGGTATCGGAAGAAACATAAGGGTCGCTGGCCAAAT 
                   
               
               
                   
                 GTGAATCAACATTCACTACTCAACCCGATAGTGAAGCAGCTTTACTTTG 
                   
               
               
                   
                 ATCAGGAGGAGATCCCACACTCTGTTGCCCTTGAGCACTATTTAGATAT 
                   
               
               
                   
                 CTCGATGATAGAATTTGAGAAGACTTTTGAAGTGGAACTATCTGATAGT 
                   
               
               
                   
                 CTAAGCATCTTTCTGAAGGATAAGTCGATAGCTTTGGATAAACAAGAAT 
                   
               
               
                   
                 GGCACAGTGGTTTTGTCTCAGAAGTGACTCCAAAGCACCTACGAATGTC 
                   
               
               
                   
                 TCGTCATGATCGCAAGTCTACCAATAGGCTATTGTTAGCCTTTATTAACT 
                   
               
               
                   
                 CCCCTGAATTCGATGTTAAGGAAGAGCTTAAATATTTGACTACAGGTGA 
                   
               
               
                   
                 GTATGCCACTGACCCAAATTTCAATGTCTCTTACTCACTGAAAGAGAAG 
                   
               
               
                   
                 GAAGTTAAGAAAGAAGGGCGCATTTTCGCAAAGATGTCACAGAAAATG 
                   
               
               
                   
                 AGAGCATGCCAGGTTATTTGTGAAGAGTTACTAGCACATCATGTGGCTC 
                   
               
               
                   
                 CTTTGTTTAAAGAGAATGGTGTTACACAATCGGAGCTATCCCTGACAAA 
                   
               
               
                   
                 GAATTTGTTGGCTATTAGCCAACTGAGTTACAACTCGATGGCCGCTAAG 
                   
               
               
                   
                 GTGCGATTGCTGAGGCCAGGGGACAAGTTCACCGCTGCACACTATATGA 
                   
               
               
                   
                 CCACAGACCTAAAAAAGTACTGCCTTAACTGGCGGCACCAGTCAGTCAA 
                   
               
               
                   
                 ATTGTTCGCCAGAAGCCTGGATCGACTATTTGGGTTAGACCATGCTTTTT 
                   
               
               
                   
                 CTTGGATACACGTCCGTCTCACCAATAGCACTATGTACGTTGCTGACCC 
                   
               
               
                   
                 ATTCAATCCACCAGACTCAGATGCATGCACAAATTTAGACGACAATAAG 
                   
               
               
                   
                 AACACTGGGATTTTTATTATAAGTGCTCGAGGTGGTATAGAAGGCCTTC 
                   
               
               
                   
                 AACAGAAACTATGGACTGGCATATCAATTGCAATCGCCCAGGCGGCAG 
                   
               
               
                   
                 CAGCCCTCGAGGGCTTACGAATTGCTGCCACTTTGCAGGGGGATAACCA 
                   
               
               
                   
                 GGTTTTAGCGATTACGAAAGAATTCATGACCCCAGTCTCGGAGGATGTA 
                   
               
               
                   
                 ATCCACGAGCAGCTATCTGAAGCGATGTCGCGATACAAGAGGACTTTCA 
                   
               
               
                   
                 CATACCTTAATTATTTAATGGGGCACCAATTGAAGGATAAAGAAACCAT 
                   
               
               
                   
                 CCAATCCAGTGACTTCTTCGTTTACTCCAAAAGGATCTTCTTCAATGGGT 
                   
               
               
                   
                 CAATCCTAAGTCAATGCCTCAAGAACTTCAGTAAACTCACTACCAATGC 
                   
               
               
                   
                 CACTACCCTTGCTGAGAACACTGTAGCCGGCTGCAGTGACATCTCCTCA 
                   
               
               
                   
                 TGCATAGCCCGTTGTGTGGAAAACGGGTTGCCTAAGGATGCTGCATATG 
                   
               
               
                   
                 TTCAGAATATAATCATGACTCGGCTTCAACTGTTGCTAGATCACTACTAT 
                   
               
               
                   
                 TCTATGCATGGTGGCATAAACTCAGAGTTAGAGCAGCCAACTCTAAGTA 
                   
               
               
                   
                 TCCCTGTCCGAAACGCAACCTATTTACCATCTCAATTAGGCGGTTACAA 
                   
               
               
                   
                 TCATTTGAATATGACCCGACTATTCTGTCGCAATATCGGTGACCCGCTTA 
                   
               
               
                   
                 CTAGTTCTTGGGCAGAGTCAAAAAGACTAATGGATGTTGGCCTTCTCAG 
                   
               
               
                   
                 TCGTAAGTTCTTAGAGGGGATATTATGGAGACCCCCGGGAAGTGGGAC 
                   
               
               
                   
                 ATTTTCAACACTCATGCTTGATCCGTTCGCACTTAACATTGATTACTTAA 
                   
               
               
                   
                 GGCCACCAGAGACAATAATCCGAAAACACACCCAAAAAGTCTTGTTGC 
                   
               
               
                   
                 AGGATTGTCCTAATCCTCTATTAGCAGGTGTAGTTGACCCGAACTACAA 
                   
               
               
                   
                 CCAGGAATTAGAATTATTAGCTCAGTTCCTGCTTGATCGGGAAACCGTT 
                   
               
               
                   
                 ATTCCCAGGGCTGCCCATGCCATCTTTGAACTGTCTGTCTTGGGAAGGA 
                   
               
               
                   
                 AAAAACATATACAAGGATTGGTTGATACTACAAAAACAATTATTCAGTG 
                   
               
               
                   
                 CTCATTAGAAAGACAGCCACTGTCCTGGAGGAAAGTTGAGAACATTGTA 
                   
               
               
                   
                 ACCTACAATGCGCAGTATTTCCTCGGGGCCACCCAGCAGGTTGACACCA 
                   
               
               
                   
                 ATATCTCAGAAAGGCAGTGGGTGATGCCAGGTAATTTCAAGAAGCTTGT 
                   
               
               
                   
                 ATCTCTTGACGATTGCTCAGTCACGTTGTCCACTGTGTCACGGCGCATTT 
                   
               
               
                   
                 CTTGGGCCAATCTACTTAACTGGAGGGCTATAGATGGTTTGGAAACTCC 
                   
               
               
                   
                 AGATGTGATAGAGAGTATTGATGGCCGCCTTGTGCAATCATCCAATCAA 
                   
               
               
                   
                 TGCGGCCTATGTAATCAAGGATTGGGCTCCTACTCCTGGTTCTTCTTGCC 
                   
               
               
                   
                 CTCCGGGTGTGTGTTCGACCGTCCACAAGATTCTCGAGTGGTTCCAAAG 
                   
               
               
                   
                 ATGCCATACGTGGGATCCAAAACGGATGAGAGACAGACTGCGTCAGTG 
                   
               
               
                   
                 CAGGCTATACAGGGATCCACATGTCACCTTAGAGCAGCATTGAGACTTG 
                   
               
               
                   
                 TATCACTCTACCTTTGGGCCTATGGAGATTCTGACATATCATGGCTAGA 
                   
               
               
                   
                 AGCCGCGACATTGGCTCAAACACGGTGCAATATTTCTCTTGATGACCTG 
                   
               
               
                   
                 CGGATCCTGAGCCCTCTTCCTTCCTCGGCAAATTTACACCACAGATTGA 
                   
               
               
                   
                 ATGACGGGGTAACACAAGTGAAATTCATGCCCGCCACATCGAGCCGGG 
                   
               
               
                   
                 TGTCAAAGTTCGTCCAAATTTGCAATGACAACCAGAATCTTATCCGTGA 
                   
               
               
                   
                 TGATGGGAGTGTTGATTCCAATATGATTTATCAGCAGGTTATGATATTA 
                   
               
               
                   
                 GGGCTTGGAGAGATTGAATGTTTGTTAGCTGACCCAATCGATACAAACC 
                   
               
               
                   
                 CAGAACAACTGATTCTTCACCTACACTCTGATAATTCTTGCTGTCTCCGG 
                   
               
               
                   
                 GAGATGCCAACGACCGGTTTTGTACCTGCTTTAGGATTGACCCCATGCT 
                   
               
               
                   
                 TAACTGTCCCAAAGCACAATCCGTATATTTATGATGATAGCCCAATACC 
                   
               
               
                   
                 CGGTGATTTGGATCAGAGGCTCATTCAAACCAAATTCTTTATGGGTTCT 
                   
               
               
                   
                 GACAATCTAGATAATCTTGATATCTACCAGCAGCGAGCTTTACTGAGTC 
                   
               
               
                   
                 GGTGTGTGGCTTATGACATTATCCAATCAGTATTCGCTTGCGATGCACC 
                   
               
               
                   
                 AGTATCTCAGAAGAATGATGCAATCCTTCACACTGACTACCATGAAAAT 
                   
               
               
                   
                 TGGATCTCAGAGTTCCGATGGGGTGACCCTCGCATAATCCAAGTAACAG 
                   
               
               
                   
                 CAGGTTACGAGTTAATTCTGTTCCTTGCATACCAGCTTTATTATCTCAGA 
                   
               
               
                   
                 GTGAGGGGTGACCGTGCAATCCTGTGTTATATTGATAGGATACTCAACA 
                   
               
               
                   
                 GGATGGTATCTTCCAATCTAGGCAGTCTCATCCAGACGCTCTCTCATCCG 
                   
               
               
                   
                 GAGATTAGGAGGAGATTTTCATTGAGTGATCAAGGGTTCCTTGTCGAAA 
                   
               
               
                   
                 GGGAGCTAGAGCCAGGTAAGCCACTGGTAAAACAAGCGGTTATGTTCC 
                   
               
               
                   
                 TAAGGGACTCAGTCCGCTGCGCTTTAGCAACTATCAAGGCAGGAATTGA 
                   
               
               
                   
                 GCCTGAGATCTCCCGAGGTGGCTGTACCCAGGATGAGCTGAGCTTTACC 
                   
               
               
                   
                 CTTAAGCACTTACTATGTCGGCGTCTCTGTATAATTGCTCTCATGCATTC 
                   
               
               
                   
                 GGAAGCAAAGAACTTGGTCAAAGTTAGAAACCTTCCAGTAGAGGAAAA 
                   
               
               
                   
                 AACCGCCTTACTATACCAGATGTTGATCACTGAGGCCAATGCCAGGAGA 
                   
               
               
                   
                 TCAGGGTCTGCTAGTATCATCATAAGCTTAGTTTCAGCACCCCAGTGGG 
                   
               
               
                   
                 ACATTCATACACCAGCGTTGTATTTTGTATCAAAGAAAATGCTGGGGAT 
                   
               
               
                   
                 GCTCAAAAGGTCAACCACACCCTTGGATATAAGTGACCTTTCTGAGAGC 
                   
               
               
                   
                 CAGAACCTCACACCAACAGAATTGAATGATGTTCCTGGTCACATGGCAG 
                   
               
               
                   
                 AGGAATTTCCCTGTTTGTTTAGCAGTTATAACGCTACATATGAAGACAC 
                   
               
               
                   
                 AATTACTTACAATCCAATGACTGAAAAACTCGCAGTGCACTTGGACAAT 
                   
               
               
                   
                 GGTTCCACCCCTTCCAGAGCGCTTGGTCGTCACTACATCCTGCGACCCCT 
                   
               
               
                   
                 TGGGCTTTACTCGTCTGCATGGTACCGGTCTGCAGCACTATTAGCGTCA 
                   
               
               
                   
                 GGGGCCCTCAGTGGGTTGCCTGAGGGGTCAAGCCTGTACTTGGGAGAG 
                   
               
               
                   
                 GGGTATGGGACCACCATGACTCTACTTGAGCCCGTTGTCAAGTCCTCAA 
                   
               
               
                   
                 CTGTTTACTACCATACATTGTTTGACCCAACCCGGAATCCTTCACAGCGG 
                   
               
               
                   
                 AACTACAAACCAGAACCGCGGGTATTCACTGATTCCATTTGGTACAAGG 
                   
               
               
                   
                 ATGATTTCACACGACCACCTGGTGGCATTGTAAATCTATGGGGTGAAGA 
                   
               
               
                   
                 CGTACGTCAGAGTGATATTACACAGAAAGACACGGTTAATTTCATATTA 
                   
               
               
                   
                 TCTCGGGTCCCGCCAAAATCACTCAAATTGATACACGTTGATATTGAGT 
                   
               
               
                   
                 TCTCCCCAGACTCTGATGTACGGACGCTACTATCTGGCTATTCCCATTGT 
                   
               
               
                   
                 GCACTATTGGCCTACTGGCTACTGCAACCTGGAGGGCGATTTGCGGTTA 
                   
               
               
                   
                 GAGTTTTCTTAAGTGACCATATCATAGTCAACTTGGTCACTGCCATTCTG 
                   
               
               
                   
                 TCCGCTTTTGACTCTAATCTGGTGTGCATTGCGTCAGGATTGACACACAA 
                   
               
               
                   
                 GGATGATGGGGCAGGTTATATTTGTGCAAAGAAGCTTGCAAATGTTGAG 
                   
               
               
                   
                 GCTTCAAGAATTGAGTATTACTTGAGGATGGTCCACGGCTGTGTTGACT 
                   
               
               
                   
                 CATTAAAAATTCCTCATCAATTAGGAATCATTAAATGGGCTGAGGGTGA 
                   
               
               
                   
                 AGTGTCCCGACTTACCAAAAAGGCGGATGATGAAATAAACTGGCGGTT 
                   
               
               
                   
                 AGGTGATCCAGTTACCAGATCATTTGATCCGGTTTCTGAGCTAATAATT 
                   
               
               
                   
                 GCGCGAACAGGGGGATCAGTATTAATGGAATACGGGACTTTTACTAACC 
                   
               
               
                   
                 TCAGGTGTGCGAACTTGGCAGATACATATAAACTTTTGGCTTCAATTGT 
                   
               
               
                   
                 AGAGACCACCTTAATGGAAATAAGGGTTGAGCAAGATCAGTTGGAAGA 
                   
               
               
                   
                 TGATTCGAGGAGACAAATCCAGGTAGTCCCTGCTTTTAATACAAGATCC 
                   
               
               
                   
                 GGGGGAAGGATCCGTACATTGATTGAGTGTGCTCAGCTGCAGGTCATAG 
                   
               
               
                   
                 ATGTTATCTGTGTGAACATAGATCACCTCTTTCCCAAACACCGACATGCT 
                   
               
               
                   
                 CTTGTCACACAACTTACTTACCAGTCAGTGTGCCTTGGGGACTTGATTGA 
                   
               
               
                   
                 AGGCCCCCAAATTAAGACATATCTAAGGGCCAGGAAGTGGATCCAACG 
                   
               
               
                   
                 TAGGGGACTCAATGAGACAATTAACCATATCATCACTGGACAAGTGTCG 
                   
               
               
                   
                 CGGAATAAGGCAAGGGATTTTTTCAAGAGGCGCCTGAAGTTGGTTGGCT 
                   
               
               
                   
                 TTTCGCTCTGTGGCGGTTGGGGCTACCTCTCACTTTAGCTGCTTAGATTG 
                   
               
               
                   
                 TTGATTATTATGAATAATCGGAGTCGAAATCGTAAATAGAAAGACATAA 
                   
               
               
                   
                 AATTGCAAATAAGCAATGATCGTATTAATATTTAATAAAAAATATGTCT 
                   
               
               
                   
                 TTTATTTCGT 
                   
               
               
                 Avian 
                 ACGAAAAAGAAGAATAAAAGGCAGAAGCCTTTTAAAAGGAACCCTGGG 
                 79 
               
               
                 paramyxovirus 
                 CTGTCGTAGGTGTGGGAAGGTTGTATTCCGAGTGCGCCTCCGAGGCATC 
                   
               
               
                 4 isolate 
                 TACTCTACACCTATCACAATGGCTGGTGTCTTCTCCCAGTATGAGAGGTT 
                   
               
               
                 Uria_aalge/ 
                 TGTGGATAACCAATCCCAAGTGTCAAGGAAGGATCATCGGTCCCTGGCA 
                   
               
               
                 Russia/Tyule- 
                 GGGGGATGCCTCAAAGTCAACATCCCTATGCTTGTCACTGCATCTGAAG 
                   
               
               
                 niy_Island/l 
                 ATCCCACCACTCGTTGGCAACTAGCATGTTTATCTTTAAGGCTCTTGATC 
                   
               
               
                 15/2015, 
                 TCCAACTCATCAACCAGCGCTATCCGCCAGGGGGCAATACTGACTCTCA 
                   
               
               
                 genome 
                 TGTCACTACCATCACAAAATATGAGAGCAACGGCAGCTATTGCTGGTTC 
                   
               
               
                 Genbank: 
                 CACAAATGCAGCTGTTATCAACACTATGGAAGTCCTAAGTGTCAACGAC 
                   
               
               
                 KU601399.1 
                 TGGACCCCATCCTTCGACCCTAGGAGCGGTCTCTCTGAAGAGGATGCTC 
                   
               
               
                   
                 AGGTTTTTAGAGACATGGCAAGGGATCTGCCCCCTCAGTTCACCTCCGG 
                   
               
               
                   
                 ATCACCCTTTACATCAGCTTTGGCGGAGGGGTTTACCCCAGAAGACACC 
                   
               
               
                   
                 CACGACCTAATGGAGGCCTTGACCAGTGTGCTGATACAGATCTGGATCC 
                   
               
               
                   
                 TGGTGGCTAAGGCCATGACCAACATTGATGGTTCTGGGGAGGCCAATGA 
                   
               
               
                   
                 GAGACGTCTTGCAAAGTATATCCAGAAGGGACAGCTCAATCGCCAGTTT 
                   
               
               
                   
                 GCAATTGGTAATCCTGCTCGTCTAATAATCCAACAGACGATCAAAAGCT 
                   
               
               
                   
                 CCTTAACTGTCCGCAGGTTCTTGGTCTCTGAGCTTCGTGCATCACGAGGT 
                   
               
               
                   
                 GCGGTGAAAGAAGGATCCCCTTATTATGCAGCTGTTGGGGATATCCACG 
                   
               
               
                   
                 CATACATCTTTAACGCAGGACTGACACCATTCTTGACTACTTTAAGATAT 
                   
               
               
                   
                 GGGATCGGCACCAAGTATGCTGCTGTTGCACTCAGTGTGTTCGCTGCAG 
                   
               
               
                   
                 ACATTGCAAAATTAAAGAGTCTACTTACCTTATACCAAGATAAGGGTGT 
                   
               
               
                   
                 GGAGGCCGGATACATGGCACTCCTTGAAGATCCAGACTCCATGCACTTT 
                   
               
               
                   
                 GCACCTGGAAACTTCCCACACATGTACTCCTACGCGATGGGGGTGGCTT 
                   
               
               
                   
                 CTTACCATGACCCCAGCATGCGCCAGTACCAATATGCCAGGAGGTTCCT 
                   
               
               
                   
                 CAGCCGACCCTTCTACTTGCTAGGAAGGGACATGGCCGCCAAGAATACA 
                   
               
               
                   
                 GGCACGCTGGATGAGCAACTGGCAAAGGAACTGCAAGTGTCAGAGAGA 
                   
               
               
                   
                 GACCGCGCCGCACTGTCCGCTGCGATTCAATCAGCAATGGAAGGGGGA 
                   
               
               
                   
                 GAATCCGACGACTTCCCACTGTCGGGATCCATGCCGGCTCTCTCCGACA 
                   
               
               
                   
                 ATGCACAACCAGTTACCCCAAGAACCCAACAGTCCCAGCTCTCCCCTCC 
                   
               
               
                   
                 CCAATCATCAAGCATGTCTCAATCAGCGCCCAGGACCCCGGACTACCAG 
                   
               
               
                   
                 CCTGATTTTGAACTGTAGGCTGCATCCATGCACCAGCAGCAGGCCAAAG 
                   
               
               
                   
                 AAACCACCCTCCTCTCCACACATCCCACCCAATCACCCGCTGAGACTCA 
                   
               
               
                   
                 ATCCAACACCCTAGCATCCCCCTCATTTAATTAAAAACTGACCAATAGG 
                   
               
               
                   
                 GTGGGGAAGGAGAGTTATTGGCTATTGCCAAGTTCGTGCAGCAATGGAT 
                   
               
               
                   
                 TTTACCGATATTGATGCTGTCAACTCATTAATCGAATCATCATCAGCAAT 
                   
               
               
                   
                 CATAGATTCCATACAGCATGGAGGGCTGCAACCATCAGGCACTGTCGGC 
                   
               
               
                   
                 CTATCGCAAATCCCAAAGGGGATAACCAGCGCTTTAACCAAAGCCTGG 
                   
               
               
                   
                 GAGGCTGAGGCAGCAAATGCTGGCAATGGGGACACCCAACAAAAGTCT 
                   
               
               
                   
                 GACAGTCTGGAGGATCATCAGGCCAACGACACAGACTCCCCCGAAGAC 
                   
               
               
                   
                 ACAGGCACTAACCAGACCATCCAGGAAACCAATATCGTTGAAACACCC 
                   
               
               
                   
                 CACCCCGAAGTGCTATCGGCAGCCAAAGCCAGACTCAAGAGGCCCAAG 
                   
               
               
                   
                 GCAGGGAAGGACACCCACGACAATCCCTCTGCGCAACCTGATCATCTTT 
                   
               
               
                   
                 TAAAGGGGGGCCCCTTGAGCCCACAACCAGTGGCACCGTGGGTGCAAA 
                   
               
               
                   
                 ATCCGCCCATTCATGGAGGTCCCGGCACCGCCGATCCCCGCCCATCACA 
                   
               
               
                   
                 AACTCAGGATCATTCCCTCACCGGAGAGAGATGGCAATCGTCACCGACA 
                   
               
               
                   
                 AAGCAACCGGAGCCATCGAACTGGTGGAATGGTGCAACCCGGGGTGCA 
                   
               
               
                   
                 CAGCAATCCGAATTGAACCTACCAGACTCGACTGTGTATGCGGACACTG 
                   
               
               
                   
                 CCCCACCATCTGCAGCCTCTGCATGTATGACGACTGATCAGGTACAACT 
                   
               
               
                   
                 ATTAATGAAGGAGGTTGCCGATATGAAATCACTCCTTCAGGCACTAGTG 
                   
               
               
                   
                 AGGAACCTAGCTGTCCTGCCTCAACTAAGGAACGAGGTTGCAGCAATCA 
                   
               
               
                   
                 GGACATCACAGGCTATGATAGAGGGGACACTTAATTCAATCAAGATTCT 
                   
               
               
                   
                 CGACCCTGGGAATTATCAGGAATCATCACTAAACAGTTGGTTCAAACCA 
                   
               
               
                   
                 CGACAAGATCACGCGGTTGTTGTGTCCGGACCAGGGAATCCATTGACCA 
                   
               
               
                   
                 TGCCAACCCCAATCCAGGACAATACCATATTCCTGGATGAATTGGCAAG 
                   
               
               
                   
                 ACCTCATCCTAGTTTGGTCAATCCGTCCCCGCCCACTACCAACACTAATG 
                   
               
               
                   
                 TTGATCTTGGCCCACAGAAGCAGGCTGCGATAGCTTATATCTCAGCAAA 
                   
               
               
                   
                 ATGCAAGGATCAAGGGAAACGAGATCAGCTCTCAAAGCTCATCGAGCG 
                   
               
               
                   
                 AGCAACCACCTTGAGTGAGATCAACAAAGTTAAAAGACAGGCTCTTGG 
                   
               
               
                   
                 CCTCTAGATCACCCAATCACCCCCAGTAATGAGTACAACAATAATCAGA 
                   
               
               
                   
                 ACCTCCCTAAACCACATGGCCAACCAAGCACACCATCCACACCACCCCT 
                   
               
               
                   
                 TACTATCCTTTGCCAGAAACTCCGCCGCAGCTGATTTATTCAAAAGAAG 
                   
               
               
                   
                 CCACTTGGTATAACCTAGCAACCGCAAGATAGGGTGGGGAAGGTGCTTT 
                   
               
               
                   
                 GCCTGCAAGAGGGCTCCCTCATCTTCAGACACTTACCCGCCAACCCACC 
                   
               
               
                   
                 AGTGACACAATGGCAGACATGGACACTGTATATATCAATCTGATGGCAG 
                   
               
               
                   
                 ATGATCCAACCCACCAAAAAGAACTGCTGTCCTTTCCCCTCATTCCAGT 
                   
               
               
                   
                 GACTGGTCCCGACGGGAAAAAGGAACTCCAACACCAGGTTCGGACTCA 
                   
               
               
                   
                 ATCCTTGCTCGCCTCAGACAAGCAAACTGAGAGGTTCATCTTCCTCAAC 
                   
               
               
                   
                 ACTTACGGGTTTATCTATGACACTACACCGGACAAGACAACTTTTTCCA 
                   
               
               
                   
                 CCCCAGAGCATATCAATCAGCCCAAGAGAACGATGGTGAGTGCTGCAA 
                   
               
               
                   
                 TGATGACCATCGGCCTGGTCCCCGCCAATATACCCTTGAACGAACTAAC 
                   
               
               
                   
                 AGCTACTGTGTTTGGCCTGAAGGTGAGAGTGAGGAAGAGTGCGAGATA 
                   
               
               
                   
                 TCGAGAGGTGGTCTGGTATCAGTGCAACCCTGTACCAGCCCTGCTGGCA 
                   
               
               
                   
                 GCCACCAGGTTCGGTCGCCAAGGGGGTCTCGAATCGAGCACTGGAGTC 
                   
               
               
                   
                 AGTGTGAAGGCCCCTGAGAAGATAGATTGTGAGAAGGATTATACTTACT 
                   
               
               
                   
                 ACCCTTATTTCCTATCTGTGTGCTACATCGCTACTTCCAACCTGTTCAAG 
                   
               
               
                   
                 GTACCAAAAATGGTTGCTAATGCGACCAACAGTCAATTATACCATCTGA 
                   
               
               
                   
                 CCATGCAGGTCACATTTGCCTTTCCAAAAAACATCCCCCCAGCTAACCA 
                   
               
               
                   
                 GAAACTCCTGACACAAGTGGATGAAGGATTCGAGGGCACTGTGGACTG 
                   
               
               
                   
                 CCATTTTGGGAACATGCTGAAAAAGGATCGGAAAGGGAATATGAGGAC 
                   
               
               
                   
                 ATTGTCGCAGGCGGCAGATAAGGTCAGACGGATGAACATCCTTGTTGGT 
                   
               
               
                   
                 ATCTTTGACTTGCATGGGCCGACACTCTTCCTGGAGTATACCGGGAAAC 
                   
               
               
                   
                 TAACAAAAGCTCTGCTAGGGTTCATGTCTACCAGCCGAACAGCAATCAT 
                   
               
               
                   
                 CCCCATATCTCAGCTCAATCCTATGCTGAGTCAACTCATGTGGAGTAGT 
                   
               
               
                   
                 GATGCCCAGATAGTAAAATTAAGAGTGGTCATAACTACATCCAAACGC 
                   
               
               
                   
                 GGCCCATGCGGGGGTGAGCAGGAGTATGTGCTGGATCCCAAATTCACA 
                   
               
               
                   
                 GTTAAAAAAGAAAAAGCCCGACTCAATCCTTTCAAGAAGGCAGCCCAA 
                   
               
               
                   
                 TGATCAAATCTGCAGGATCTCAGAAATCAGACCACTCTATACTATCCAC 
                   
               
               
                   
                 TGATTAATAGACACGTAGCTATACAGTTGATGAACCTATGAAGAATCAA 
                   
               
               
                   
                 TTAGCAAACCGAATCCTTGCTAGGGTGGGGAAGGAGTTGATTGGGTGTC 
                   
               
               
                   
                 TAAACAAAAGCACTCCTTTGCACCTCCTCGCCACGAAACAACCATAATG 
                   
               
               
                   
                 AGGTTATCACGCACAATCCTGGCCCTGATTCTAGGCACACTTACCGGCT 
                   
               
               
                   
                 ATTTAATGGATGCCCACTCCACCACTGTGAACGAGAGACCAAAGTCTGA 
                   
               
               
                   
                 AGGGATTAGGGGTGATCTTATACCAGGCGCAGGTATCTTTGTAACTCAA 
                   
               
               
                   
                 GTCCGACAACTACAGATCTACCAACAGTCTGGGTATCATGACCTTGTCA 
                   
               
               
                   
                 TCAGGTTATTACCTCTTCTACCGGCAGAACTCAATGATTGTCAAAGGGA 
                   
               
               
                   
                 AGTTGTCACAGAGTACAACAATACGGTATCACAGCTGTTGCAGCCTATC 
                   
               
               
                   
                 AAAACCAACCTGGATACCTTATTGGCTGATGGTGGTACAAGGGATGCCG 
                   
               
               
                   
                 ATATACAGCCGCGGTTCATTGGGGCGATAATAGCCACAGGTGCCCTGGC 
                   
               
               
                   
                 GGTGGCTACGGTAGCTGAGGTGACTGCAGCCCAAGCACTATCGCAGTCG 
                   
               
               
                   
                 AAAACGAACGCTCAAAATATTCTCAAGTTGAGAGATAGTATTCAGGCCA 
                   
               
               
                   
                 CCAACCAGGCAGTTTTTGAAATTTCACAAGGACTTGAGGCAACTGCAAC 
                   
               
               
                   
                 TGTGCTATCAAAACTGCAAACTGAGCTCAATGAGAACATTATCCCAAGC 
                   
               
               
                   
                 CTGAACAACTTGTCCTGTGCTGCTATGGGGAATCGCCTTGGTGTATCACT 
                   
               
               
                   
                 ATCACTCTACTTGACCTTAATGACCACCCTATTTGGGGACCAGATCACA 
                   
               
               
                   
                 AACCCAGTGCTGACACCAATCTCCTATAGCACTCTATCGGCAATGGCAG 
                   
               
               
                   
                 GTGGTCACATTGGCCCGGTGATGAGTAAGATATTAGCCGGATCTGTCAC 
                   
               
               
                   
                 AAGTCAGTTGGGGGCAGAACAGTTGATTGCTAGCGGCTTAATACAGTCA 
                   
               
               
                   
                 CAAGTAGTGGGTTATGATTCCCAATATCAATTATTGGTTATCAGGGTCA 
                   
               
               
                   
                 ATCTTGTACGGATTCAAGAGGTCCAGAATACGAGGGTCGTATCACTAAG 
                   
               
               
                   
                 AACACTAGCGGTCAATAGGGATGGTGGACTTTATAGAGCCCAGGTGCCT 
                   
               
               
                   
                 CCTGAGGTAGTTGAACGGTCTGGCATTGCAGAGCGATTTTACGCAGATG 
                   
               
               
                   
                 ATTGCGTTCTTACTACAACTGATTACATTTGCTCATCGATCCGATCTTCT 
                   
               
               
                   
                 CGGCTTAATCCAGAGTTAGTCAAGTGTCTCAGTGGGGCACTTGATTCAT 
                   
               
               
                   
                 GCACATTTGAGAGGGAAAGTGCATTATTGTCAACCCCTTTCTTTGTATAC 
                   
               
               
                   
                 AACAAGGCAGTTGTCGCAAATTGTAAAGCAGCAACATGTAGATGTAAT 
                   
               
               
                   
                 AAACCGCCGTCTATTATTGCCCAATACTCTGCATCGGCTCTGGTCACCAT 
                   
               
               
                   
                 CACCACTGACACCTGCGCCGACCTTGAAATTGAGGGTTATCGCTTCAAC 
                   
               
               
                   
                 ATACAGACTGAATCCAACTCATGGGTTGCACCAAACTTCACTGTCTCGA 
                   
               
               
                   
                 CTTCACAGATTGTATCAGTTGATCCAATAGACATCTCCTCTGACATTGCC 
                   
               
               
                   
                 AAAATCAACAGTTCCATCGAGGCTGCAAGAGAGCAGCTGGAACTAAGC 
                   
               
               
                   
                 AACCAGATCCTCTCCCGGATTAACCCACGAATCGTGAATGATGAATCAC 
                   
               
               
                   
                 TGATAGCTATTATCGTGACAATTGTTGTGCTTAGTCTCCTCGTAATCGGT 
                   
               
               
                   
                 CTGATTGTTGTTCTCGGTGTGATGTATAAGAATCTTAAGAAAGTCCAAC 
                   
               
               
                   
                 GAGCTCAAGCTGCCATGATGATGAAGCAAATGAGCTCATCACAGCCTGT 
                   
               
               
                   
                 GACCACTAAATTAGGGACGCCTTTCTAGGAGGATAATCATATTACTCTA 
                   
               
               
                   
                 CTCAATGATGAGCAAGACGTACCAATTATCAATGATTGTGTCACAAGGC 
                   
               
               
                   
                 CGGTTGGGAATGCACCGAATCTCTCCCCTTTCTTTTTAATTAAAAACATT 
                   
               
               
                   
                 TGAAGTGAGGATAAGAGGGGGGAAGAGTATGGTAGGGTGGGGAAGGT 
                   
               
               
                   
                 AGCCAATCCCTGCCTATTAGGCTGATCGTATCAAAAGAACCCAACAGAA 
                   
               
               
                   
                 GTCTAGATACAGGGCAACATGGAGGGCAGCCGTGATAATCTAACAGTG 
                   
               
               
                   
                 GATGATGAATTAAAGACAACATGGAGGTTAGCTTATAGAGTTGTGTCCC 
                   
               
               
                   
                 TCCTATTGATGGTGAGCGCTTTGATAATCTCTATAGTAATCCTGACAAG 
                   
               
               
                   
                 AGATAACAGCCAAAGCATAATCACGGCGATCAACCAGTCATCTGACGC 
                   
               
               
                   
                 AGACTCTAAGTGGCAAACGGGAATAGAAGGGAAAATCACCTCCATTAT 
                   
               
               
                   
                 GACTGATACGCTCGATACCAGAAATGCAGCCCTTCTCCACATTCCACTC 
                   
               
               
                   
                 CAGCTCAACACGCTTGCGGCGAACCTATTGTCCGCCCTTGGAGGCAACA 
                   
               
               
                   
                 CAGGAATTGGCCCCGGAGATCTGGAACACTGCCGTTACCCTGTTCATGA 
                   
               
               
                   
                 CACCGCTTACCTGCATGGAGTTAATCGATTACTCATCAACCAGACAGCT 
                   
               
               
                   
                 GATTATACAGCAGAAGGCCCCCTAGATCATGTGAACTTCATACCAGCCC 
                   
               
               
                   
                 CGGTTACGACCACTGGATGCACAAGGATACCATCCTTTTCTGTGTCATC 
                   
               
               
                   
                 GTCCATTTGGTGCTATACACACAACGTGATTGAAACCGGTTGCAATGAC 
                   
               
               
                   
                 CACTCAGGTAGTAACCAATATATCAGCATGGGAGTCATTAAGAGAGCA 
                   
               
               
                   
                 GGCAACGGCTTACCTTACTTCTCAACAGTTGTAAGTAAGTATCTGACTG 
                   
               
               
                   
                 ATGGGTTGAATAGGAAGAGCTGTTCTGTAGCTGCCGGATCTGGGCATTG 
                   
               
               
                   
                 CTACCTCCTTTGCAGCTTAGTGTCGGAGCCTGAACCTGATGACTATGTAT 
                   
               
               
                   
                 CACCTGATCCCACACCGATGAGGTTAGGGGTGCTAACGTGGGATGGGTC 
                   
               
               
                   
                 TTACACTGAACAGGTGGTACCCGAAAGAATATTCAAGAACATATGGAG 
                   
               
               
                   
                 TGCAAACTACCCGGGAGTAGGGTCAGGTGCTATAGTAGGAAATAAAGT 
                   
               
               
                   
                 GTTATTCCCATTTTACGGCGGAGTGAGGAATGGATCGACCCCGGAGGTG 
                   
               
               
                   
                 ATGAATAGGGGAAGATACTACTACATCCAGGATCCAAATGACTATTGCC 
                   
               
               
                   
                 CTGACCCGCTGCAAGATCAGATCTTAAGAGCGGAACAATCGTATTACCC 
                   
               
               
                   
                 AACTCGATTCGGTAGGAGGATGGTAATGCAAGGGGTCCTAGCATGTCCA 
                   
               
               
                   
                 GTATCCAACAATTCAACAATAGCAAGCCAATGTCAATCTTACTATTTTA 
                   
               
               
                   
                 ATAACTCATTAGGGTTCATCGGGGCAGAATCTAGAATCTATTATCTCAA 
                   
               
               
                   
                 TGGTAACATTTATCTTTATCAGAGAAGCTCGAGTTGGTGGCCTCACCCC 
                   
               
               
                   
                 CAAATCTACCTGCTTGATTCTAGAATTGCAAGTCCGGGTACTCAGACCA 
                   
               
               
                   
                 TTGACTCAGGTGTCAATCTCAAAATGTTAAATGTCACTGTGATTACACG 
                   
               
               
                   
                 ACCATCATCTGGTTTTTGTAATAGTCAGTCACGATGCCCTAATGATTGCT 
                   
               
               
                   
                 TATTCGGGGTCTATTCGGATATCTGGCCTCTTAGCCTTACCTCAGATAGC 
                   
               
               
                   
                 ATATTCGCATTCACAATGTATTTACAGGGGAAGACAACACGTATTGACC 
                   
               
               
                   
                 CGGCTTGGGCGCTATTCTCCAATCATGCAATTGGGCATGAGGCTCGTCT 
                   
               
               
                   
                 GTTTAATAAGGAAGTTAGTGCTGCTTATTCTACCACCACTTGTTTTTCGG 
                   
               
               
                   
                 ACACCATCCAAAATCAGGTGTATTGCCTGAGTATACTTGAGGTCAGAAG 
                   
               
               
                   
                 TGAGCTCTTGGGAGCATTCAAAATAGTACCATTCCTCTACCGCGTCTTGT 
                   
               
               
                   
                 AGGCATCCATTCAGCCAAAAAACTTGAGTGACCATGAGATTGACACCTG 
                   
               
               
                   
                 ATCCCCCTCAAAGACACCTATCTAAATTACTGTTCTAGACCCATGATTA 
                   
               
               
                   
                 GGTACCTTCTTAATCAATCATTTGGTTTTTAATTAAAAATGGAAAAATG 
                   
               
               
                   
                 GACCTAGTTCCAAGAGAGGGCTGGAACCCATTAGGGTGGGGAAGGATT 
                   
               
               
                   
                 GCTTTGCTCCTTGACTCACACTCACGTACACTCGATCAGACTTCTGTTAA 
                   
               
               
                   
                 AAAGGAAACCTTCTCAAACTCGCCCCACGATGTCCAATCAGGCAGCTGA 
                   
               
               
                   
                 GATTATACTACCTAGCTTCCATCTAGAATCACCCTTAATCGAGAATAAG 
                   
               
               
                   
                 TGCTTCTATTATATGCAATTACTTGGTCTCGTGTTGCCACATGATCACTG 
                   
               
               
                   
                 GAGATGGAGGGCATTCGTTAACTTTACAGTGGATCAGGTGCACCTTAAA 
                   
               
               
                   
                 AATCGTAATCCCCGCTTAATGGCCCACATCGACTACACTAAAGATAGAT 
                   
               
               
                   
                 TGAGGACTCATGGTGTCTTAGGTTTCCACCAGACTCAGACAAGTTTGAG 
                   
               
               
                   
                 CCGTTATCGTGTTTTGCTCCATCCTGAAACCTTACCTTGGCTGTCAGCCA 
                   
               
               
                   
                 TGGGAGGATGCATCAATCAGGTGCCTAAAGCATGGCGGAACACCCTGA 
                   
               
               
                   
                 AATCGATCGAGCACAGTGTAAAGCAGGAGGCACCTCAACTAAAGCTAC 
                   
               
               
                   
                 TCATGGAGAGAACCTCATTAAAATTAACTGGGGTACCTTACTTGTTCTCT 
                   
               
               
                   
                 AATTGCAATCCCGGGAAAACCAAAGCAGGAACTATACCTGTCCTAAGT 
                   
               
               
                   
                 GAGATGGCATCGGAACTCTTGTCAAATCCTATCTCCCAATTCCAATCAA 
                   
               
               
                   
                 CATGGGGATGTGCTGCTTCGGGGTGGCACCATGTAGTCAGTATCATGAG 
                   
               
               
                   
                 GCTTCAGCAATATCAAAGAAGGACAGGTAAGGAGGAAAAAGCAATCAC 
                   
               
               
                   
                 TGAAGTTCAGTATGGCACAGACACCTGTCTCATTAACGCAGACTACACC 
                   
               
               
                   
                 GTTGTTTTTTCCACACAGAACCGTATCATAACGGTCTTGCCTTTCGATGT 
                   
               
               
                   
                 TGTCCTCATGATGCAAGACCTGCTCGAATCCCGACGGAATGTCCTGTTC 
                   
               
               
                   
                 TGTGCCCGCTTTATGTATCCCAGAAGCCAACTTCATGAGAGGATAAGTA 
                   
               
               
                   
                 CAATATTAGCCCTTGGAGACCAATTGGGGAGGAAAGCACCCCAAGTCCT 
                   
               
               
                   
                 GTATGATTTTGTAGCAACCCTTGAGTCATTTGCATACGCAGCGGTTCAA 
                   
               
               
                   
                 CTTCATGACAACAATCCTACCTACGGTGGGGCCTTCTTTGAATTCAACAT 
                   
               
               
                   
                 CCAAGAGTTAGAATCGATTCTGTCCCCTGCACTTAGTAAGGATCAGGTC 
                   
               
               
                   
                 AACTTCTACATAAGTCAAGTTGTCTCAGCGTACAGTAACCTTCCTCCATC 
                   
               
               
                   
                 CGAATCGGCAGAGCTGCTGTGCCTGTTACGCCTGTGGGGTCATCCCTTG 
                   
               
               
                   
                 CTAAACAGCCTTGATGCAGCAAAGAAAGTCAGGGAGTCTATGTGCGCC 
                   
               
               
                   
                 GGGAAGGTTCTCGATTACAACGCCATTCGACTTGTCTTGTCTTTTTATCA 
                   
               
               
                   
                 TACGTTGCTAATCAATGGGTACCGGAAGAAACACAAGGGTCGCTGGCC 
                   
               
               
                   
                 AAATGTGAATCAACATTCACTTCTCAACCCGATAGTGAGGCAGCTTTAT 
                   
               
               
                   
                 TTTGATCAGGAGGAGATCCCACACTCTGTTGCCCTTGAGCACTATTTGG 
                   
               
               
                   
                 ATGTTTCAATGATAGAATTTGAAAAAACTTTTGAAGTGGAACTATCTGA 
                   
               
               
                   
                 CAGCCTAAGCATCTTCCTGAAGGATAAGTCGATAGCTTTGGATAAGCAA 
                   
               
               
                   
                 GAATGGTATAGTGGTTTTGTCTCAGAAGTGACTCCGAAGCACCTGCGAA 
                   
               
               
                   
                 TGTCCCGTCATGATCGCAAGTCTACCAATAGGCTCCTGTTAGCCTTCATT 
                   
               
               
                   
                 AACTCCCCTGAATTCGATGTTAAGGAAGAGCTTAAATACTTGACTACGG 
                   
               
               
                   
                 GTGAGTACGCCACTGACCCAAATTTCAATGTCTCATACTCACTTAAAGA 
                   
               
               
                   
                 GAAGGAGGTAAAGAAAGAAGGGCGCATTTTCGCAAAAATGTCACAAAA 
                   
               
               
                   
                 GATGAGAGCGTGCCAGGTTATTTGTGAAGAATTGCTAGCACATCATGTG 
                   
               
               
                   
                 GCTCCTTTGTTTAAAGAGAATGGTGTTACTCAATCAGAGCTATCCCTGA 
                   
               
               
                   
                 CAAAAAATTTGTTGGCTATTAGCCAACTGAGTTACAACTCGATGGCCGC 
                   
               
               
                   
                 TAAGGTTCGATTGCTGCGGCCAGGGGACAAGTTCACTGCTGCACACTAT 
                   
               
               
                   
                 ATGACCACAGACCTAAAAAAGTACTGTCTTAATTGGCGGCACCAGTCAG 
                   
               
               
                   
                 TCAAACTGTTCGCCAGAAGCCTGGATCGACTGTTTGGGTTAGACCATGC 
                   
               
               
                   
                 TTTTTCTTGGATACATGTCCGTCTCACCAACAGCACTATGTACGTTGCTG 
                   
               
               
                   
                 ACCCCTTTAATCCACCAGACTCAGATGCATGCACAAATTTAGACGACAA 
                   
               
               
                   
                 TAAGAATACCGGGATCTTTATTATAAGTGCACGAGGTGGTATAGAAGGC 
                   
               
               
                   
                 CTCCAACAAAAGCTATGGACTGGCATATCAATTGCAATTGCCCAAGCGG 
                   
               
               
                   
                 CAGCGGCCCTCGAAGGCTTACGAATTGCTGCTACTCTGCAGGGGGATAA 
                   
               
               
                   
                 CCAAGTTTTGGCGATTACAAAGGAATTCATGACCCCAGTCCCAGAAGAT 
                   
               
               
                   
                 GTAATCCATGAGCAGCTATCTGAGGCGATGTCTCGATACAAAAGGACTT 
                   
               
               
                   
                 TCACATACCTCAATTATTTAATGGGACATCAGTTGAAGGATAAGGAAAC 
                   
               
               
                   
                 CATCCAATCTAGTGATTTCTTTGTTTACTCCAAAAGAATCTTCTTCAATG 
                   
               
               
                   
                 GATCAATCTTAAGTCAATGCCTCAAGAACTTCAGTAAACTCACTACTAA 
                   
               
               
                   
                 TGCCACTACCCTTGCTGAGAATACTGTGGCCGGCTGCAGTGACATCTCT 
                   
               
               
                   
                 TCATGCATTGCCCGTTGTGTGGAAAACGGGTTGCCAAAGGATGCCGCAT 
                   
               
               
                   
                 ACATCCAGAATATAATCATGACTCGGCTTCAACTATTGCTAGATCATTA 
                   
               
               
                   
                 CTATTCAATGCATGGCGGCATAAACTCAGAGTTAGAGCAGCCAACGTTA 
                   
               
               
                   
                 AGTATCTCTGTTCGAAACGCAACCTACTTACCATCTCAACTAGGCGGTT 
                   
               
               
                   
                 ACAATCATTTAAATATGACTCGACTATTCTGCCGCAATATCGGCGACCC 
                   
               
               
                   
                 GCTTACCAGTTCTTGGGCAGAGTCAAAAAGACTAATGGATGTTGGTCTC 
                   
               
               
                   
                 CTCAGTCGTAAGTTCTTGGAGGGGATATTATGGAGACCCCCGGGAAGTG 
                   
               
               
                   
                 GGACGTTTTCAACACTCATGCTTGATCCGTTCGCACTTAACATTGATTAC 
                   
               
               
                   
                 CTGAGGCCGCCAGAGACAATTATCCGAAAACACACCCAAAAAGTCTTA 
                   
               
               
                   
                 TTGCAAGATTGTCCAAACCCCCTATTAGCAGGTGTCGTTGACCCAAACT 
                   
               
               
                   
                 ACAACCAAGAATTAGAGCTGTTAGCTCAGTTCTTGCTTGATCGGGAAAC 
                   
               
               
                   
                 CGTTATTCCCAGGGCTGCCCATGCCATCTTTGAGTTGTCTGTCTTGGGGA 
                   
               
               
                   
                 GGAAAAAACATATACAAGGATTGGTAGATACTACAAAAACAATTATTC 
                   
               
               
                   
                 AGTGCTCATTGGAAAGACAGCCATTGTCCTGGAGGAAAGTTGAGAACA 
                   
               
               
                   
                 TTGTTACCTACAACGCGCAGTATTTCCTCGGGGCCACCCAACAGGCTGA 
                   
               
               
                   
                 CACTAATGTCTCAGAAGGGCAGTGGGTGATGCCAGGTAACTTCAAGAA 
                   
               
               
                   
                 GCTTGTGTCCCTTGACGATTGCTCGGTCACGTTGTCTACCGTATCACGGC 
                   
               
               
                   
                 GCATATCGTGGGCCAATCTACTGAACTGGAGAGCTATAGACGGTTTGGA 
                   
               
               
                   
                 AACCCCGGATGTGATAGAGAGTATCGATGGCCGCCTTGTACAATCATCC 
                   
               
               
                   
                 AATCAATGTGGCCTATGTAATCAAGGGTTGGGGTCCTACTCCTGGTTCTT 
                   
               
               
                   
                 CTTGCCCTCTGGGTGTGTGTTCGACCGTCCACAAGATTCCCGGGTGGTTC 
                   
               
               
                   
                 CAAAGATGCCATATGTGGGGTCCAAAACAGATGAGAGACAGACTGCAT 
                   
               
               
                   
                 CAGTGCAAGCTATACAAGGATCCACTTGTCACCTCAGGGCGGCATTGAG 
                   
               
               
                   
                 GCTTGTATCACTCTACCTATGGGCCTATGGGGATTCTGACATATCATGGC 
                   
               
               
                   
                 TAGAAGCTGCGACACTGGCTCAAACACGGTGCAACGTTTCTCTTGATGA 
                   
               
               
                   
                 CTTGCGAATCTTGAGCCCTCTCCCTTCTTCGGCGAATTTACACCACAGAT 
                   
               
               
                   
                 TAAATGACGGGGTAACACAGGTTAAATTCATGCCCGCCACATCGAGCCG 
                   
               
               
                   
                 AGTGTCAAAGTTCGTCCAAATTTGCAATGACAACCAGAATCTTATCCGT 
                   
               
               
                   
                 GACGATGGAAGTGTTGATTCCAATATGATTTATCAACAGGTTATGATAT 
                   
               
               
                   
                 TAGGGCTTGGGGAGATTGAATGCTTGTTAGCTGACCCAATTGATACAAA 
                   
               
               
                   
                 CCCAGAACAATTGATTCTTCATCTACACTCTGATAATTCTTGCTGTCTCC 
                   
               
               
                   
                 GGGAGATGCCAACGACCGGCTTTGTACCAGCTCTAGGACTGACCCCATG 
                   
               
               
                   
                 TTTAACTGTCCCAAAGCACAATCCTTACATATATGATGATAGCCCAATA 
                   
               
               
                   
                 CCTGGTGATTTGGATCAGAGGCTCATTCAGACCAAATTTTTCATGGGTTC 
                   
               
               
                   
                 TGACAATTTGGATAATCTTGATATCTACCAACAGCGAGCTTTACTGAGT 
                   
               
               
                   
                 AGGTGTGTGGCTTATGATGTTATCCAATCGATCTTTGCTTGTGATGCACC 
                   
               
               
                   
                 AGTCTCTCAGAAGAATGACGCAATCCTTCACACTGACTATCATGAGAAT 
                   
               
               
                   
                 TGGATCTCAGAGTTCCGATGGGGTGACCCTCGTATTATCCAAGTAACGG 
                   
               
               
                   
                 CAGGCTACGAGTTAATTCTGTTCCTTGCATACCAGCTTTATTATCTCAGA 
                   
               
               
                   
                 GTGAGAGGTGATCGTGCAATCCTGTGTTATGTTGACAGGATACTCAATA 
                   
               
               
                   
                 GGATGGTATCTTCCAATCTAGGCAGTCTCATCCAGACACTCTCTCATCCA 
                   
               
               
                   
                 GAGATTAGGAGGAGATTCTCGTTGAGTGATCAAGGGTTCCTTGTTGAGA 
                   
               
               
                   
                 GGGAACTAGAGCCAAGTAAGCCCTTGGTTAAACAAGCGGTTATGTTCTT 
                   
               
               
                   
                 GAGGGACTCAGTCCGCTGCGCTCTAGCTACTATCAAGGCAGGAATTGAG 
                   
               
               
                   
                 CCTGAGATCTCCCGAGGTGGCTGTACTCAGGATGAGCTAAGCTTTACTC 
                   
               
               
                   
                 TTAAGCACTTACTGTGTCGGCGTCTCTGTGTAATCGCTCTCATGCATTCA 
                   
               
               
                   
                 GAGGCAAAGAACTTGGTTAAGGTTAGAAACCTTCCTGTAGAAGAGAAA 
                   
               
               
                   
                 ACCGCCTTACTGTATCAGATGTTGGTCACTGAGGCCAATGCTAGGAAAT 
                   
               
               
                   
                 CAGGATCTGCTAGCATTATCATAAACCTAGTATCGGCACCCCAGTGGGA 
                   
               
               
                   
                 TATTCATACACCAGCATTGTATTTTGTGTCAAAGAAAATGTTAGGGATG 
                   
               
               
                   
                 CTTAAGAGGTCAACCACACCCTTGGATATAAGTGACCTCTCTGAGAGCC 
                   
               
               
                   
                 AGAATCCCGCACCGGCAGAGCTGAATGATGTTCCTGATCACATGGCAGA 
                   
               
               
                   
                 AGAATTTCCCTGTTTGTTTAGTAGTTATAACGCTACATATGAAGACACA 
                   
               
               
                   
                 ATCACTTACAATCCAATGACTGAAAAACTCGCCTTGCACTTGGACAATA 
                   
               
               
                   
                 GTTCCACCCCATCCAGAGCACTTGGTCGTCACTACATCCTGCGGCCTCTT 
                   
               
               
                   
                 GGGCTTTACTCATCTGCATGGTACCGGTCTGCAGCACTACTAGCATCAG 
                   
               
               
                   
                 GGGCCCTAAATGGGTTGCCTGAGGGGTCAAGCCTGTATCTAGGAGAAG 
                   
               
               
                   
                 GGTACGGGACCACCATGACTCTGCTTGAGCCCGTTGTCAAGTCTTCAAC 
                   
               
               
                   
                 TGTTTACTACCACACATTGTTTGACCCAACCCGGAATCCTTCACAGCGG 
                   
               
               
                   
                 AACTATAAACCAGAACCACGGGTATTCACGGATTCTATTTGGTACAAGG 
                   
               
               
                   
                 ATGATTTCACACGGCCACCTGGTGGTATTATCAACCTGTGGGGTGAAGA 
                   
               
               
                   
                 TATACGTCAGAGTGATATCACACAGAAAGACACGGTCAACTTCATACTA 
                   
               
               
                   
                 TCTCAGATCCCGCCAAAGTCACTTAAGTTGATACACGTTGATATTGAAT 
                   
               
               
                   
                 TCTCACCAGACTCCGATGTACGGACACTACTTTCTGGCTATTCTCATTGT 
                   
               
               
                   
                 GCATTATTGGCCTACTGGCTATTGCAACCTGGAGGGCGATTTGCGGTTA 
                   
               
               
                   
                 GGGTTTTCTTAAGTGACCATGTCATAGTAAACTTGGTCACTGCAATTCTG 
                   
               
               
                   
                 TCTGCTTTTGACTCTAATTTGGTGTGCATTGCATCAGGATTGACACACAA 
                   
               
               
                   
                 GGATGATGGGGCAGGTTATATTTGCGCAAAGAAGCTTGCAAATGTTGAG 
                   
               
               
                   
                 GCTTCAAGGATTGAATACTACCTGAGGATGGTCCATGGTTGTGTTGACT 
                   
               
               
                   
                 CATTAAAGATCCCTCATCAATTAGGAATCATTAAATGGGCCGAGGGTGA 
                   
               
               
                   
                 GGTGTCCCAACTTACCAGAAAGGCAGATGATGAAATAAATTGGCGGTT 
                   
               
               
                   
                 AGGTGATCCGGTTACCAGATCATTTGATCCAGTTTCTGAGCTAATCATTG 
                   
               
               
                   
                 CACGAACAGGGGGGTCTGTATTGATGGAATACGGGGCTTTTACTAACCT 
                   
               
               
                   
                 CAGGTGTGCGAACTTGGCAGATACATACAAACTTCTGGCTTCAATTGTA 
                   
               
               
                   
                 GAGACCACCTTAATGGAAATAAGGGTTGAACAAGACCAGTTGGAAGAT 
                   
               
               
                   
                 AATTCGAGGAGGCAAATCCAAATAGTCCCCGCTTTTAACACGAGATCTG 
                   
               
               
                   
                 GGGGAAGGATCCGTACACTGATTGAGTGTGCTCAGCTGCAGATTATAGA 
                   
               
               
                   
                 TGTTATTTGTGTAAACATAGATCACCTCTTTCCTAGACACCGACATGTTC 
                   
               
               
                   
                 TTGTCACGCAACTTACCTACCAGTCGGTGTGCCTTGGGGACTTGATTGA 
                   
               
               
                   
                 AGGCCCCCAAATTAAGACGTATCTGAGGGCCAGAAAGTGGATCCAACG 
                   
               
               
                   
                 TCGGGGACTCAATGAGACAGTTAACCATATCATCACTGGACAAGTGTCA 
                   
               
               
                   
                 CGGAATAAAGCAAGGGATTTTTTCAAGAGGCGCCTGAAGTTGGTTGGCT 
                   
               
               
                   
                 TTTCACTCTGCGGTGGTTGGAGCTACCTCTCACTTTAACTGTTCAAGTTG 
                   
               
               
                   
                 TTGATTATTATGAATAATCGGAGTCGGAATCGTAAATAGTAAGCCACAA 
                   
               
               
                   
                 AGTCGTGAATAAACAATGATTGCATTAGTATTTAATAAAAAATATGTCT 
                   
               
               
                   
                 TTTATTTCGT 
                   
               
               
                 Avian 
                 ACGAAAAAGAAGAATAAAAGGCAGAAGCCTTTTAAAAGGAACCCTGGG 
                 80 
               
               
                 paramyxovirus 
                 CTGTCGTAGGTGTGGGAAGGTTGTATTCCGAGCGCGCCTCCGAGGCATC 
                   
               
               
                 4 isolate 
                 TACTCTACACCTATCACAATGGCTGGTGTCTTCTCCCAATATGAGAGGTT 
                   
               
               
                 APMV- 
                 TGTGGACAATCAATCCCAAGTGTCAAGGAAGGATCATCGGTCCCTGGCA 
                   
               
               
                 4/Egyptian 
                 GGGGGATGCCTTAAAGTCAACATTCCTATGCTTGTCACTGCATCTGAAG 
                   
               
               
                 goose/South 
                 ATCCCACCACTCGTTGGCAACTAGCGTGTTTATCTTTGAGGCTCTTGATC 
                   
               
               
                 Africa/N146 
                 TCCAACTCATCAACCAGTGCTATCCGCCAGGGGGCAATACTGACTCTCA 
                   
               
               
                 8/2010, 
                 TGTCACTACCATCACAAAATATGAGAGCAACGGCAGCTATTGCTGGTTC 
                   
               
               
                 complete 
                 CACAAATGCAGCTGTTATCAACACTATGGAAGTCTTGAGTGTCAATGAC 
                   
               
               
                 genome 
                 TGGACCCCATCCTTCGACCCTAGGAGCGGTCTCTCTGAAGAGGATGCTC 
                   
               
               
                 Genbank: 
                 AGGTTTTCAGAGACATGGCAAAGGACCTGCCCCCTCAGTTCACCTCCGG 
                   
               
               
                 JX133079.1 
                 ATCACCCTTTACATCAGCATTGGCGGAGGGGTTTACCCCAGAAGACACC 
                   
               
               
                   
                 CACGACCTAATGGAGGCCTTGACTAGTGTGCTGATACAGATCTGGATCC 
                   
               
               
                   
                 TGGTGGCTAAGGCCATGACCAACATTGATGGCTCTGGAGAGGCCAATG 
                   
               
               
                   
                 AGAGACGTCTTGCAAAGTACATCCAGAAGGGACAACTCAATCGCCAGT 
                   
               
               
                   
                 TTGCAATTGGTAATCCTGCTCGTCTGATAATCCAACAGACGATCAAAAG 
                   
               
               
                   
                 CTCCTTAACTGTCCGCAGATTCTTGGTCTCTGAACTTCGTGCATCACGAG 
                   
               
               
                   
                 GTGCGGTGAAAGAAGGATCCCCTTACTATGCAGCTGTTGGGGACATCCA 
                   
               
               
                   
                 CGCTTACATCTTTAACGCAGGACTGACACCATTCTTGACTACCTTAAGAT 
                   
               
               
                   
                 ATGGGATCGGCACCAAGTATGCTGCAGTTGCACTCAGTGTGTTCGCTGC 
                   
               
               
                   
                 AGACATTGCAAAATTAAAGAGCCTACTTACCCTATATCAAGACAAGGGT 
                   
               
               
                   
                 GTGGAGGCTGGATACATGGCACTCCTTGAAGATCCAGACTCCATGCACT 
                   
               
               
                   
                 TTGCACCTGGAAACTTCCCACACATGTACTCCTACGCGATGGGGGTGGC 
                   
               
               
                   
                 TTCTTACCATGACCCCAGCATGCGCCAGTACCAATATGCTAGGAGGTTC 
                   
               
               
                   
                 CTCAGCCGACCTTTCTACTTGCTAGGGAGGGACATGGCCGCCAAGAACA 
                   
               
               
                   
                 CAGGCACGCTGGATGAGCAACTGGCAAAGGAACTGCAAGTGTCAGAAA 
                   
               
               
                   
                 GAGACCGCGCCGCATTGTCCGCTGCGATTCAGTCAGCAATAGAGGGGG 
                   
               
               
                   
                 GAGAATCCGACGACTTCCCACTGTCGGGATCCATGCCGGCTCTCTCCGA 
                   
               
               
                   
                 CAATGCGCAACCAGTTACCCCAAGAACCCAACAGTCCCAGCCCTCCCCT 
                   
               
               
                   
                 CCCCAATCATCAAGCATGTCTCAATCAGCACCCAAGACCCCGGACTACC 
                   
               
               
                   
                 AGCCTGATTTTGAACTGTAGGCTGCATCAGTGCACCAACAGCAGGCCAA 
                   
               
               
                   
                 AGGGACCACCCTCCTCCCCACACATCCCACCCAATCACCCGCTGAGACC 
                   
               
               
                   
                 CAATCCAACACCCCAGCATCCCCCTCATTTAATTAAAAACTGACCAATA 
                   
               
               
                   
                 GGGTGGGGAAGGAGAGCTGTTGGCTATCGCCAAGATCGTGCAGCGATG 
                   
               
               
                   
                 GATTTTACCGATATTGATGCTGTCAACTCATTAATTGAATCATCATCAGC 
                   
               
               
                   
                 AATCATAGATTCCATACAGCATGGAGGGCTGCAACCATCAGGTACTGTT 
                   
               
               
                   
                 GGCCTATCGCAAATCCCCAAGGGGATAACCAGCGCTTTAACCAAGGCCT 
                   
               
               
                   
                 GGGAGGCTGAGACAGCAACTGCTGGCTACGGGGACACCCAACACAAAT 
                   
               
               
                   
                 CTGACAGTCCGGAGGATCATCAGGCCAACGACACAGACTCCCCCGAAG 
                   
               
               
                   
                 ACACAGGCACCAACCAGACCATCCAGGAAGCCAACATCGTCGAAACAC 
                   
               
               
                   
                 CCCACCCCGAAGTTCTATCGGCAGCCAAAGCCAGACTCAAGAGGCCCA 
                   
               
               
                   
                 AGGCAGGGAAGGACACCCACGACAATCCCCCTGCGCAACCCGATCCCC 
                   
               
               
                   
                 TTTTAAAGGGGGGCCCCCTGAGCCCACAACCAGCAGCACCGTGGGTGC 
                   
               
               
                   
                 AAAATTCACCCATTCATGGAGGTCCCGGCACCGCCGATCCCCGCCCATC 
                   
               
               
                   
                 ACAAACTCAGGATCATTCCCTCACCGGAGAGAGATGGCAATCGTCACCG 
                   
               
               
                   
                 ATAAAGCAACCGGAGACATTGAACTGGTGGAATGGTGCAACCCGGGGT 
                   
               
               
                   
                 GCACAGCAATCCGAACTGAACCAACCAGACTCGACTGTGTATGCGGAT 
                   
               
               
                   
                 ACTGCCCCACCATCTGCAGCCTCTGCATGTATGACGACTGATCAGGTAC 
                   
               
               
                   
                 AACTATTAATGAAGGAGGTTGCCGATATGAAATCACTCCTTCAGGCACT 
                   
               
               
                   
                 AGTGAGGAACCTAGCTGTCCTGCCTCAACTAAGGAACGAGGTTGCAGC 
                   
               
               
                   
                 AATCAGGACATCACAGGCTATGATAGAGGGGACACTCAATTCAATCAA 
                   
               
               
                   
                 GATTCTCGACCCTGGGAATTATCAAGAATCATCACTGAACAGTTGGTTC 
                   
               
               
                   
                 AAACCACGCCAAGATCACGCGGTTGCTGTGTCCGGACCAGGGAATCCAT 
                   
               
               
                   
                 TGACCATGCCAACTCCAATCCAAGACAACACCATATTCCTGGATGAACT 
                   
               
               
                   
                 GGCAAGACCTCATCCTAGTTTGGTCAATCCGTCCCCGCCCACTACCAAC 
                   
               
               
                   
                 ACTAATGTTGACCTTGGCCCACAGAAGCAGGCTGCGATAGCTTATATCT 
                   
               
               
                   
                 CAGCAAAATGCAAGGATCAAGGGAGACGAGATCAGCTCTCAAAGCTCA 
                   
               
               
                   
                 TCGAGCGAGCAACCACCTTGAGTGAGATCAACAAAGTCAAAAGACAGG 
                   
               
               
                   
                 CCCTTGGCCTCTAGACCACTCGACCACCCCCAGTAATGAACACAACAAT 
                   
               
               
                   
                 AATCAGAACCTCCCTAAACCACACGGCCAACCCAGCACACCATCCACAC 
                   
               
               
                   
                 CGCCCACCACTATCCCCCGCCAAAAACTCCGCTGCAGCCGATTTATTCA 
                   
               
               
                   
                 AAAGAAGCCACTTGATATGACTTATCAACCGCAAGGTAGGGTGGGGAA 
                   
               
               
                   
                 GGTGCTTTGCCTGCAAGAGGGCTCCCTCATCTTCAGACACGTACCCGCC 
                   
               
               
                   
                 AACCCACCAGTGACGCAATGGCAGACATGGACACTGTATATATCAATCT 
                   
               
               
                   
                 GATGGCAGATGATCCAACCCACCAAAAAGAACTGCTGTCCTTCCCTCTC 
                   
               
               
                   
                 ATTCCAGTGACTGGTCCCGACGGGAAAAAGGAACTCCAACACCAGGTT 
                   
               
               
                   
                 CGGACTCAATCCTTGCTCGCCTCAGACAAGCAAACTGAGAGGTTCATCT 
                   
               
               
                   
                 TCCTCAACACTTACGGGTTTATCTATGACACTACACCGGACAAGACAAC 
                   
               
               
                   
                 TTTTTCCACCCCAGAGCATATCAATCAGCCCAAGAGAACGATGGTGAGT 
                   
               
               
                   
                 GCTGCAATGATGACCATCGGCCTGGTCCCCGCCAATATACCCTTGAACG 
                   
               
               
                   
                 AACTAACAGCTACTGTGTTTGGCCTGAAAGTAAGAGTGAGGAAGAGTG 
                   
               
               
                   
                 CGAGATATCGAGAGGTGGTCTGGTATCAGTGCAACCCTGTACCAGCCCT 
                   
               
               
                   
                 GCTTGCAGCCACCAGGTTTGGTCGCCAAGGAGGTCTCGAATCGAGCACT 
                   
               
               
                   
                 GGAGTCAGTGTGAAGGCCCCCGAGAAGATAGATTGCGAGAAGGATTAT 
                   
               
               
                   
                 ACTTACTACCCTTATTTCCTATCTGTGTGCTACATCGCCACTTCTAACCT 
                   
               
               
                   
                 GTTCAAGGTACCAAAAATGGTTGCTAATGCGACCAACAGTCAATTATAC 
                   
               
               
                   
                 CACCTGACGATGCAGGTCACATTTGCCTTTCCAAAAAACATTCCCCCAG 
                   
               
               
                   
                 CTAACCAGAAACTCCTGACACAAGTGGATGAAGGATTCGAGGGCACTG 
                   
               
               
                   
                 TGGACTGCCATTTTGGGAACATGCTGAAAAAGGATCGGAAAGGGAATA 
                   
               
               
                   
                 TGAGGACATTGTCGCAGGCGGCAGATAAGGTCCGACGGATGAACATCC 
                   
               
               
                   
                 TTGTTGGTATCTTTGACTTGCATGGGCCGACACTCTTCCTGGAGTATACC 
                   
               
               
                   
                 GGGAAACTAACGAAAGCTCTGTTAGGGTTCATGTCTACCAGCCGAACAG 
                   
               
               
                   
                 CAATCATCCCCATATCTCAGCTCAATCCTATGCTGAGTCAACTCATGTGG 
                   
               
               
                   
                 AGCAGTGATGCTCAGATAGTAAAATTAAGAGTGGTCATAACTACATCCA 
                   
               
               
                   
                 AACGCGGCCCATGCGGGGGTGAGCAGGAATATGTGCTGGACCCCAAAT 
                   
               
               
                   
                 TCACAGTTAAAAAAGAAAAAGCCCGACTCAACCCTTTCAAGAAGGCAG 
                   
               
               
                   
                 CTTAATGATCAAATCTGCAGGATCTCAGGAATCAGACCACTCTATACTA 
                   
               
               
                   
                 TCTACTGATCAATAGATATGTAGCTATACAGTTGATGAACCTATGAAGA 
                   
               
               
                   
                 ATCAATTAGCAAACCGAATCCTTGCTAGGGTGGGGAAGGAATTGATTGG 
                   
               
               
                   
                 GTGTCTAAACAAAAGCACTTCTTTGCACCTACTCACCACAAAACAATCA 
                   
               
               
                   
                 TAATGAGGTTATCACGAACAATCCTGGCCCTGATTCTCGGCGCACTTAC 
                   
               
               
                   
                 CGGCTATTTAATGGATGCCCACTCCACCACTGTGAATGAGAGACCAAAG 
                   
               
               
                   
                 TCTGAGGGGATTAGGGGTGACCTTATACCAGGTGCAGGAATCTTTGTAA 
                   
               
               
                   
                 CTCAAATCCGGCAACTACAGATCTACCAACAATCTGGGTATCATGACCT 
                   
               
               
                   
                 TGTCATCAGGTTATTACCTCTTTTACCGGCAGAACTCAATGATTGCCAAA 
                   
               
               
                   
                 GGGAAGTTGTCACAGAGTACAACAATACAGTATCACAGCTGTTGCAGCC 
                   
               
               
                   
                 TATCAAAACTAACCTGGATACCTTATTGGCTGATGGTGGCACAAGGGAT 
                   
               
               
                   
                 GCCGATATACAGCCGCGGTTCATTGGGGCGATAATAGCCACAGGTGCCC 
                   
               
               
                   
                 TGGCAGTGGCTACGGTAGCTGAGGTGACTGCAGCCCAAGCACTATCTCA 
                   
               
               
                   
                 GTCGAAAACGAACGCTCAAAATATTCTCAAGTTGAGAGATAGTATTCAG 
                   
               
               
                   
                 GCCACCAACCAGGCAGTTTTTGAAATTTCACAAGGACTTGAGGCAACTG 
                   
               
               
                   
                 CAACTGTACTATCAAAACTGCAAGCTGAGCTCAATGAGAACATTATCCC 
                   
               
               
                   
                 AAGTCTGAACAACTTGTCCTGTGCTGCCATGGGGAATCGCCTTGGTGTA 
                   
               
               
                   
                 TCACTATCACTCTACTTGACCCTAATGACTACCCTATTTGGGGACCAGAT 
                   
               
               
                   
                 CACAAACCCAGTGCTGACACCAATCTCCTATAGCACTTTATCGGCAATG 
                   
               
               
                   
                 GCAGGTGGTCACATTGGCCCGGTGATGAGTAAAATATTAGCCGGATCTG 
                   
               
               
                   
                 TCACAAGTCAGTTGGGGGCAGAACAGTTGATTGCTAGCGGCTTAATACA 
                   
               
               
                   
                 ATCACAGGTAGTAGGTTATGATTCCCAATATCAATTATTGGTTATCAGG 
                   
               
               
                   
                 GTCAACCTTGTACGGATTCAAGAGGTCCAGAATACGAGGGTCGTATCAC 
                   
               
               
                   
                 TAAGAACACTAGCGGTCAATAGGGATGGTGGACTTTATAGAGCCCAGG 
                   
               
               
                   
                 TGCCTCCCGAGGTAGTCGAACGGTCTGGCATTGCAGAGCGATTTTATGC 
                   
               
               
                   
                 AGATGATTGTGTTCTTACTACAACTGATTACATTTGCTCCTCGATCCGAT 
                   
               
               
                   
                 CTTCTCGGCTTAATCCAGAGTTAGTCAAATGTCTCAGTGGGGCACTTGA 
                   
               
               
                   
                 TTCATGCACATTTGAGAGGGAAAGTGCATTATTGTCAACCCCTTTCTTTG 
                   
               
               
                   
                 TATACAACAAGGCAGTTGTCGCAAATTGTAAAGCGGCAACATGTAGAT 
                   
               
               
                   
                 GCAATAAACCGCCGTCTATTATTGCCCAATACTCTGCATCAGCTCTGGTC 
                   
               
               
                   
                 ACCATCACCACCGACACCTGCGCCGACCTTGAAATTGAGGGCTATCGCT 
                   
               
               
                   
                 TCAATATACAGACTGAATCCAACTCATGGGTTGCACCAAACTTCACTGT 
                   
               
               
                   
                 CTCGACTTCACAGATTGTATCAGTTGATCCAATAGACATCTCCTCTGACA 
                   
               
               
                   
                 TTGCTAAAATCAACAGTTCCATCGAGGCTGCAAGAGAGCAGCTGGAACT 
                   
               
               
                   
                 AAGCAACCAGATCCTTTCCCGAATTAACCCACGAATTGTGAATGATGAA 
                   
               
               
                   
                 TCATTGATAGCTATTATCGTGACAATTGTTGTGCTTAGTCTCCTCGTAAT 
                   
               
               
                   
                 CGGTCTGATTGTTGTTCTCGGTGTGATGTATAAGAATCTTAAAAAAGTC 
                   
               
               
                   
                 CAACGAGCTCAAGCTGCCATGATGATGCAGCAGATGAGCTCATCACAG 
                   
               
               
                   
                 CCCGTGACCACTAAATTAGGGACGCCCTTCTAGGATAATAATCATATCA 
                   
               
               
                   
                 CTCTACTCAATGATGAGCAAGACGTACCAATCATCAATGATTGTGTCAC 
                   
               
               
                   
                 AAGGCCGGTAGGGAATGCACCGAATTTCTCCCCTTTCTTTTTAATTAAA 
                   
               
               
                   
                 AACATTTGTAGTGAGGATGAGAAGGGGAAAATGTTTGGTAGGGTGGGG 
                   
               
               
                   
                 AAGGTAGCCAATTCCTGCCTATTAGGCCGACCGTATCAAAAGAACTCAA 
                   
               
               
                   
                 CAGAAGTCCAGATACAAGGTAACATGGAGGGCAGCCGTGATAATCTTA 
                   
               
               
                   
                 CAGTGGATGATGAATTAAAGACAACGTGGAGGTTAGCTTATAGAGTTGT 
                   
               
               
                   
                 GTCCCTTCTATTGATGGTGAGCGCTTTGATAATCTCTATAGTAATCCTGA 
                   
               
               
                   
                 CGAGAGATAACAGCCAAAGCGTAATCACGGCGATCAACCAGTCATCTG 
                   
               
               
                   
                 AAGCTGACTCCAAGTGGCAAACGGGAATAGAAGGGAAAATCACCTCCA 
                   
               
               
                   
                 TTATGACTGATACGCTCGATACCAGGAATGCAGCCCTTCTCCACATTCC 
                   
               
               
                   
                 ACTCCAGCTCAACTCGCTTGAGGCGAACCTATTGTCCGCCCTTGGGGGC 
                   
               
               
                   
                 AACACAGGAATTGGCCCCGGAGATATAGAGCACTGCCGTTACCCTGTTC 
                   
               
               
                   
                 ATGACACCGCTTACCTGCATGGAGTTAATCGATTACTCATCAACCAGAC 
                   
               
               
                   
                 AGCTGATTATACAGCAGAAGGCCCCCTAGATCATGTGAACTTCATTCCA 
                   
               
               
                   
                 GCCCCGGTTACGACCACTGGATGCACAAGGATACCATCCTTTTCCGTGT 
                   
               
               
                   
                 CATCGTCCATTTGGTGCTATACACACAACGTGATTGAAACCGGTTGCAA 
                   
               
               
                   
                 TGACCACTCAGGTAGTAACCAATATATCAGCATGGGAGTCATTAAGAGA 
                   
               
               
                   
                 GCGGGCAACGGCCTACCTTACTTCTCAACAGTTGTAAGTAAGTATCTGA 
                   
               
               
                   
                 CTGATGGGTTGAATAGGAAAAGCTGTTCTGTAGCTGCCGGATCTGGGCA 
                   
               
               
                   
                 TTGCTACCTCCTTTGCAGCTTGGTGTCGGAGCCCGAATCTGATGACTATG 
                   
               
               
                   
                 TGTCACCTGATCCTACACCGATGAGGTTAGGGGTGCTAACGTGGGATGG 
                   
               
               
                   
                 GTCTTACACTGAGCAGGTGGTACCCGAAAGAATATTCAAGAACATATGG 
                   
               
               
                   
                 AGTGCAAACTACCCAGGAGTAGGGTCAGGTGCTATAGTAGGAAATAAG 
                   
               
               
                   
                 GTGTTATTCCCATTTTACGGCGGAGTGAGTAATGGATCGACCCCGGAGG 
                   
               
               
                   
                 TGATGAATAGGGGAAGATATTACTACATCCAGGATCCAAATGACTATTG 
                   
               
               
                   
                 CCCTGACCCGCTGCAAGATCAGATCTTAAGGGCGGAACAATCGTATTAC 
                   
               
               
                   
                 CCAACTCGATTCGGTAGGAGGATGGTGATGCAAGGGGTCCTAGCATGTC 
                   
               
               
                   
                 CAGTATCCAACAATTCAACAATAGCAAGCCAATGTCAATCTTACTATTT 
                   
               
               
                   
                 TAATAACTCATTAGGGTTCATTGGGGCAGAATCTAGGATCTATTACCTC 
                   
               
               
                   
                 AATGATAACATTTATCTTTACCAGAGAAGCTCGAGCTGGTGGCCTCACC 
                   
               
               
                   
                 CCCAGATTTACCTGCTTGATTCTAGGATTGCAAGTCCGGGTACTCAGAA 
                   
               
               
                   
                 CATTGACTCAGGTGTCAATCTCAAGATGTTAAATGTCACTGTAATTACA 
                   
               
               
                   
                 CGACCATCATCTGGTTTTTGTAATAGTCAGTCACGATGCCCTAATGACTG 
                   
               
               
                   
                 CTTATTCGGGGTCTACTCGGATATCTGGCCTCTTAGCCTTACCTCAGATA 
                   
               
               
                   
                 GCATATTCGCATTCACAATGTATTTACAGGGGAAGACAACACGTATTGA 
                   
               
               
                   
                 CCCGGCTTGGGCGCTATTCTCCAATCATGCGATTGGGCATGAGGCTCGT 
                   
               
               
                   
                 CTGTTTAATAAGAAGGTTAGTGCTGCTTATTCTACCACCACTTGTTTTTC 
                   
               
               
                   
                 GGACACCGTCCAAAATCAGGTGTATTGCCTGAGTATACTTGAGGTCAGG 
                   
               
               
                   
                 AGTGAGCTCTTGGGAGCATTCAAAATAGTACCATTCCTCTATCGCGTCTT 
                   
               
               
                   
                 GTAGGCATCCATTCAGCCAGAAAACTTGAGTGACCATGATATTAACACC 
                   
               
               
                   
                 TGATCCCCCTCAAAGACACCTATCTAAATTACTGTTCTAGACTCATGATT 
                   
               
               
                   
                 AGGTACCTTCTTAATCAATCATTTGGTTTTTAATTAAAAATGAAAAAAT 
                   
               
               
                   
                 AGGCCTAGTTCCAAGAGAGGGCTGGAACCCATTAGGGTGGGGAAGGAT 
                   
               
               
                   
                 TGCTTTGCTCCTTGACTCACACACACGTACACTCGATCAGACTCCTGTTT 
                   
               
               
                   
                 AAAAGGAATCCTTCTCAAACTCGCCCCACGATGTCCAATCAGGCGGCTG 
                   
               
               
                   
                 AGATTATACTACCCACCTTCCATCTAGAATCACCCTTAATCGAAAATAA 
                   
               
               
                   
                 GTGCTTCTATTATATGCAATTACTTGGTCTCGTGTTGCCACATGATCACT 
                   
               
               
                   
                 GGAGATGGAGGGCATTCGTTAACTTTACAGTGGATCAGGTGCACCTTAA 
                   
               
               
                   
                 AAATCGTAATCCCCGCTTGATGGCCCACATCGACTACACTAAGGATAGA 
                   
               
               
                   
                 TTAAGGACTCATGGTGTCTTAGGTTTCCACCAGACTCAGACAAGTTTGA 
                   
               
               
                   
                 GCCGTTATCGTGTTTTGCTCCATCCTGAAACCTTATCTTGGCTATCAGCC 
                   
               
               
                   
                 ATGGGGGGATGCATCAATCAGGTTCCTAAAGCATGGCGGAACACTCTG 
                   
               
               
                   
                 AAATCGATCGAGCACAGTGTAAAGCAGGAGGCACCTCAACTAAAGCTA 
                   
               
               
                   
                 CTCATGGAGAGAACCTCATTAAAATTAACTGGAGTACCTTACTTGTTCT 
                   
               
               
                   
                 CTAATTGCAATCCCGGGAAAACCACAGCAGGTACTATGCCTGTCCTAAG 
                   
               
               
                   
                 TGAGATGGCATCGGAACTCTTGTCGAATCCTATCTCCCAATTCCAATCA 
                   
               
               
                   
                 ACATGGGGGTGTGCTGCTTCGGGGTGGCACCATGTAGTCAGTATCATGA 
                   
               
               
                   
                 GGCTCCAACAATACCAAAGAAGGACAGGTAAAGAAGAGAAAGCGATC 
                   
               
               
                   
                 ACTGAAGTTCAGTATGGCACAGACACCTGTCTCATTAATGCAGACTACA 
                   
               
               
                   
                 CTGTTGTGTTTTCCACACAGAACCGTATCATAACAGTCTTGCCTTTTGAT 
                   
               
               
                   
                 GTTGTCCTCATGATGCAAGACCTGCTCGAATCCCGACGGAATGTCCTGT 
                   
               
               
                   
                 TCTGTGCCCGCTTTATGTATCCCAGAAGCCAACTTCATGAGAGGATAAG 
                   
               
               
                   
                 TACAATATTAGCTCTTGGAGACCAACTGGGGAGAAAAGCACCCCAAGT 
                   
               
               
                   
                 CCTGTATGATTTCGTAGCAACCCTTGAGTCATTTGCATACGCGGCTGTTC 
                   
               
               
                   
                 AACTTCATGACAACAATCCTACCTACGGTGGGGCCTTCTTTGAATTCAA 
                   
               
               
                   
                 TATCCAAGAGTTAGAATCCATTCTGTCCCCTGCACTTAGTAAGGATCAG 
                   
               
               
                   
                 GTCAACTTCTACATAAATCAAGTTGTCTCAGCGTACAGTAACCTTCCCCC 
                   
               
               
                   
                 ATCTGAATCGGCAGAATTGCTGTGCCTGTTACGCCTGTGGGGTCACCCC 
                   
               
               
                   
                 CTGCTAAACAGCCTTGATGCAGCAAAGAAAGTCAGGGAGTCTATGTGC 
                   
               
               
                   
                 GCCGGGAAGGTTCTCGATTACAACGCCATTCGACTTGTCTTGTCTTTTTA 
                   
               
               
                   
                 TCATACGTTGCTAATCAACGGATACCGGAAGAAACACAAGGGTCGCTG 
                   
               
               
                   
                 GCCAAATGTGAATCAACATTCACTCCTCAACCCGATAGTGAGGCAGCTT 
                   
               
               
                   
                 TATTTTGATCAGGAGGAGATCCCACACTCTGTTGCTCTTGAGCACTATTT 
                   
               
               
                   
                 GGACGTCTCAATGGTAGAATTTGAAAAAACTTTTGAAGTGGAATTATCT 
                   
               
               
                   
                 GACAGCCTAAGCATCTTCCTAAAGGATAAGTCGATAGCTTTGGATAAGC 
                   
               
               
                   
                 AAGAGTGGTACAGTGGTTTTGTCTCAGAAGTGACTCCGAAGCACCTGCG 
                   
               
               
                   
                 AATGTCCCGTCATGATCGCAAGTCTACCAATAGGCTCCTGTTAGCCTTC 
                   
               
               
                   
                 ATTAACTCCCCTGAATTCGATGTTAAGGAAGAGCTTAAATACTTGACTA 
                   
               
               
                   
                 CGGGTGAGTACGCCACTGACCCAAATTTCAATGTCTCATACTCACTTAA 
                   
               
               
                   
                 AGAGAAGGAAGTAAAGAAAGAGGGGCGCATTTTCGCAAAAATGTCACA 
                   
               
               
                   
                 AAAGATGAGAGCATGCCAGGTTATTTGTGAAGAATTGCTAGCACATCAT 
                   
               
               
                   
                 GTGGCTCCTTTGTTTAAAGAGAATGGTGTTACTCAATCAGAGCTATCCCT 
                   
               
               
                   
                 GACAAAAAATTTGTTGGCTATTAGCCAACTGAGTTACAACTCGATGGCC 
                   
               
               
                   
                 GCTAAGGTGCGATTGCTGAGACCAGGGGACAAGTTCACTGCTGCACACT 
                   
               
               
                   
                 ATATGACCACAGACCTAAAAAAGTACTGTCTTAATTGGCGGCACCAGTC 
                   
               
               
                   
                 AGTCAAACTGTTCGCCAGAAGCCTGGATCGACTGTTTGGGTTAGACCAT 
                   
               
               
                   
                 GCTTTTTCTTGGATACATGTCCGCCTCACCAACAGCACTATGTACGTTGC 
                   
               
               
                   
                 TGACCCCTTCAATCCACCAGACTCAGATGCATGCATTAATTTAGACGAC 
                   
               
               
                   
                 AATAAGAACACTGGGATTTTTATTATAAGTGCACGAGGTGGTATAGAAG 
                   
               
               
                   
                 GCCTCCAACAAAAACTATGGACTGGCATATCAATTGCAATTGCCCAAGC 
                   
               
               
                   
                 GGCAGCGGCCCTCGAAGGCTTACGAATTGCTGCTACTCTGCAGGGGGAT 
                   
               
               
                   
                 AACCAAGTTTTGGCGATTACAAAGGAATTCATGACCCCAGTCCCAGAGG 
                   
               
               
                   
                 ATGTAATCCATGAGCAGCTATCTGAGGCGATGTCTCGATACAAAAGGAC 
                   
               
               
                   
                 TTTCACATACCTCAATTATTTAATGGGACATCAATTGAAGGATAAGGAA 
                   
               
               
                   
                 ACCATCCAATCCAGTGATTTCTTTGTCTATTCCAAAAGAATCTTCTTCAA 
                   
               
               
                   
                 TGGATCAATCTTAAGTCAATGCCTCAAGAACTTCAGTAAACTCACTACT 
                   
               
               
                   
                 AATGCCACTACCCTTGCTGAGAATACTGTGGCCGGCTGCAGTGACATCT 
                   
               
               
                   
                 CTTCATGCATTGCCCGTTGTGTGGAAAACGGGTTGCCTAAGGATGCCGC 
                   
               
               
                   
                 ATATATCCAGAATATAATCATGACTCGGCTTCAATTATTGCTAGATCATT 
                   
               
               
                   
                 ACTATTCAATGCATGGCGGCATAAACTCAGAATTAGAGCAGCCAACTTT 
                   
               
               
                   
                 AAGTATCTCTGTTCGAAACGCAACCTACTTACCATCTCAACTAGGCGGT 
                   
               
               
                   
                 TACAATCATCTAAATATGACCCGACTATTCTGCCGCAATATCGGCGACC 
                   
               
               
                   
                 CGCTTACCAGTTCTTGGGCGGAGTCAAAAAGACTAATGGATGTTGGTCT 
                   
               
               
                   
                 CCTCAGTCGTAAGTTCTTGGAGGGGATATTATGGAGACCCCCGGGAAGT 
                   
               
               
                   
                 GGGACGTTTTCAACACTCATGCTTGACCCGTTCGCACTTAACATTGATTA 
                   
               
               
                   
                 CCTGAGGCCGCCAGAAACAATTATCCGAAAACACACCCAAAAAGTCTT 
                   
               
               
                   
                 GTTGCAAGATTGCCCAAACCCCCTATTAGCAGGTGTCGTTGACCCAAAC 
                   
               
               
                   
                 TACAACCAAGAATTAGAGCTGTTAGCTCAGTTCTTGCTTGATCGGGAGA 
                   
               
               
                   
                 CCGTTATTCCCAGGGCTGCCCATGCCATCTTTGAGTTGTCTGTCTTGGGG 
                   
               
               
                   
                 AGGAAAAAACATATACAAGGATTGGTGGACACTACAAAAACAATTATT 
                   
               
               
                   
                 CAGTGCTCATTGGAAAGACAGCCATTGTCCTGGAGGAAAGTTGAGAAC 
                   
               
               
                   
                 ATTGTTACCTACAACGCGCAGTATTTCCTCGGGGCCACCCAACAGGCTG 
                   
               
               
                   
                 ATACTAATGTCTCAGAAGGGCAGTGGGTGATGCCAGGTAACTTCAAGA 
                   
               
               
                   
                 AGCTTGTGTCCCTTGACGATTGCTCGGTCACGTTGTCTACTGTATCACGG 
                   
               
               
                   
                 CGCATATCGTGGGCCAATCTACTGAACTGGAGAGCTATAGATGGTTTGG 
                   
               
               
                   
                 AAACCCCGGATGTGATAGAGAGTATTGATGGCCGCCTTGTACAATCATC 
                   
               
               
                   
                 AAATCAATGTGGCCTATGTAATCAAGGGTTGGGGTCCTACTCTTGGTTC 
                   
               
               
                   
                 TTCTTGCCCTCTGGGTGTGTGTTCGACCGTCCACAAGATTCCCGGGTAGT 
                   
               
               
                   
                 TCCAAAGATGCCATACGTGGGGTCCAAAACAGATGAGAGACAGACTGC 
                   
               
               
                   
                 ATCAGTGCAAGCTATACAAGGATCCACTTGTCACCTCAGGGCAGCATTG 
                   
               
               
                   
                 AGGCTTGTATCACTCTACTTATGGGCTTATGGAGATTCTGACATATCATG 
                   
               
               
                   
                 GCTAGAAGCTGCGACACTGGCTCAAACACGGTGCAATGTTTCTCTTGAT 
                   
               
               
                   
                 GACTTGCGAATCTTGAGCCCTCTCCCTTCTTCGGCGAATTTACACCACAG 
                   
               
               
                   
                 ATTAAATGACGGGGTAACACAGGTTAAATTCATGCCCGCCACATCGAGC 
                   
               
               
                   
                 CGAGTGTCAAAGTTCGTCCAAATTTGCAATGACAACCAAAATCTTATCC 
                   
               
               
                   
                 GTGATGATGGGAGTGTTGATTCCAATATGATTTATCAACAGGTTATGAT 
                   
               
               
                   
                 ATTAGGGCTTGGGGAGATTGAATGCTTGTTAGCTGACCCAATTGATACA 
                   
               
               
                   
                 AACCCAGAACAATTGATTCTTCATCTACACTCTGATAATTCTTGCTGTCT 
                   
               
               
                   
                 CCGGGAGATGCCAACGACTGGCTTTGTACCTGCTCTAGGACTGACCCCA 
                   
               
               
                   
                 TGTTTAACTGTCCCAAAGCACAATCCTTACATTTATGATGATAGCCCAAT 
                   
               
               
                   
                 ACCTGGTGATTTGGATCAGAGGCTCATTCAGACCAAATTTTTCATGGGT 
                   
               
               
                   
                 TCTGACAATTTGGATAATCTTGATATCTACCAACAGCGAGCTTTACTGA 
                   
               
               
                   
                 GCAGGTGTGTGGCTTATGATGTTATCCAATCGATCTTTGCCTGTGATGCA 
                   
               
               
                   
                 CCAGTCTCTCAGAAGAATGACGCAATCCTTCACACTGACTATCATGAGA 
                   
               
               
                   
                 ATTGGATCTCAGAGTTCCGATGGGGTGACCCTCGTATTATCCAAGTAAC 
                   
               
               
                   
                 GGCAGGCTACGAGTTAATTCTGTTCCTTGCATACCAGCTTTATTATCTCA 
                   
               
               
                   
                 GAGTGAGGGGTGACCGTGCAATCCTGTGTTATATTGACAGGATACTCAA 
                   
               
               
                   
                 TAGGATGGTATCTTCCAATCTAGGCAGTCTCATCCAGACACTCTCTCATC 
                   
               
               
                   
                 CAGAGATTAGGAGGAGATTCTCATTGAGTGATCAAGGGTTCCTTGTTGA 
                   
               
               
                   
                 AAGGGAATTAGAGCCAGGTAAGCCCTTGGTTAAGCAAGCGGTTATGTTC 
                   
               
               
                   
                 TTGAGGGACTCGGTCCGCTGCGCTTTAGCAACTATCAAGGCAGGAATTG 
                   
               
               
                   
                 AGCCTGAGATCTCCCGAGGTGGCTGTACTCAGGATGAGCTGAGCTTTAC 
                   
               
               
                   
                 TCTTAAGCACTTACTATGCCGGCGTCTCTGTGTAATCGCTCTCATGCATT 
                   
               
               
                   
                 CAGAAGCAAAGAACTTGGTTAAAGTCAGAAACCTTCCTGTAGAGGAGA 
                   
               
               
                   
                 AAACCGCCTTACTGTACCAAATGTTGGTCACTGAGGCCAATGCTAGGAA 
                   
               
               
                   
                 GTCAGGATCTGCTAGCATTATCATAAACCTAGTCTCGGCACCCCAGTGG 
                   
               
               
                   
                 GACATTCATACACCAGCACTGTATTTTGTGTCAAAGAAAATGCTAGGGA 
                   
               
               
                   
                 TGCTTAAGAGGTCAACCACACCCTTGGATATAAGTGACCTCTCCGAGAG 
                   
               
               
                   
                 CCAGAATTCCGCACCTGCAGAGCTGACTGATGTTCCTGGTCACATGGCA 
                   
               
               
                   
                 GAAGAGTTTCCCTGTTTGTTTAGTAGTTATAACGCCACATATGAAGACA 
                   
               
               
                   
                 CAATTACTTACAATCCAACGACTGAAAAACTCGCCTTGCACTTGGACAA 
                   
               
               
                   
                 CAGTTCCACCCCATCCAGAGCACTTGGCCGTCACTACATCCTGCGGCCT 
                   
               
               
                   
                 CTTGGGCTTTATTCATCCGCATGGTACCGGTCTGCAGCACTACTAGCGTC 
                   
               
               
                   
                 AGGGGCCTTGAATGGGTTGCCTGAGGGGTCAAGCCTGTATCTAGGAGA 
                   
               
               
                   
                 AGGGTACGGGACCACCATGACTCTGCTTGAGCCCGTTGTCAAGTCTTCA 
                   
               
               
                   
                 ACTGTTTACTACCATACATTGTTTGACCCAACCCGGAATCCTTCTCAGCG 
                   
               
               
                   
                 GAACTATAAGCCAGAACCACGGGTATTCACGGATTCTATTTGGTACAAG 
                   
               
               
                   
                 GATGATTTCACACGGCCACCTGGTGGTATTATCAACCTGTGGGGTGAAG 
                   
               
               
                   
                 ATATACGGCAGAGTGATATCACACAGAAAGACACGGTCAACTTCATACT 
                   
               
               
                   
                 ATCTCAGATCCCGCCAAAATCACTTAAGTTGATACACGTTGATATTGAA 
                   
               
               
                   
                 TTCTCACCAGACTCCGATGTACGGACACTACTATCTGGCTATTCTCATTG 
                   
               
               
                   
                 TGCACTATTAGCCTACTGGCTATTGCAACCTGGAGGGCGATTTGCAGTT 
                   
               
               
                   
                 AGGGTTTTCTTAAGTGACCATATCATAGTAAACTTAGTCACTGCAATTCT 
                   
               
               
                   
                 GTCTGCTTTTGACTCTAATTTGGTGTGCATTGCATCAGGATTGACACACA 
                   
               
               
                   
                 AGGATGATGGGGCAGGTTATATTTGCGCAAAGAAGCTTGCAAATGTTGA 
                   
               
               
                   
                 GGCTTCAAGGATTGAGCACTACTTGAGGATGGTCCATGGTTGCGTTGAC 
                   
               
               
                   
                 TCATTAAAGATCCCTCATCAATTAGGAATCATTAAATGGGCCGAGGGTG 
                   
               
               
                   
                 AGGTGTCCCAACTTACCAGAAAGGCGGATGATGAAATAAATTGGCGGT 
                   
               
               
                   
                 TAGGCGATCCTGTTACCAGATCATTTGATCCAGTTTCTGAGCTAATCATT 
                   
               
               
                   
                 GCACGAACAGGGGGGTCTGTATTAATGGAATACGGGGCTTTTACTAACC 
                   
               
               
                   
                 TCAGGTGTGCGAACTTGGCAGATACATACAAGCTTCTGGCTTCAATTGT 
                   
               
               
                   
                 AGAGACCACCCTAATGGAAATAAGGGTTGAGCAAGATCAGTTGGAAGA 
                   
               
               
                   
                 TAATTCGAGGAGACAAATCCAAGTAGTCCCCGCTTTCAACACGAGATCT 
                   
               
               
                   
                 GGGGGAAGGATCCGTACGCTGATTGAGTGTGCTCAGCTGCAGATTATAG 
                   
               
               
                   
                 ATGTTATTTGTGTAAACATAGACCACCTCTTTCCTAAACACCGACATGTT 
                   
               
               
                   
                 CTTGTCACGCAACTTACCTACCAGTCGGTGTGCCTTGGGGACCTGATTG 
                   
               
               
                   
                 AAGGCCCCCAAATTAAGACGTATCTAAGGGCCAGAAAGTGGATCCAAC 
                   
               
               
                   
                 GTCAGGGACTCAATGAGACAGTTAACCATATCATCACTGGACAAGTGTC 
                   
               
               
                   
                 ACGGAATAAAGCAAGGGATTTTTTCAAGAGGCGCTTGAAGTTGGTTGGG 
                   
               
               
                   
                 TTTTCACTCTGCGGTGGTTGGAGCTACCTCTCACTTTAGCTGTTCAGGTT 
                   
               
               
                   
                 GTCGATTATTATGAATAATCGGAGTCGGAATCGCAAATAGGAAGCCAC 
                   
               
               
                   
                 AAAGTTGTGGAGAAACAATGATTGCATTAGTATTTAATAAAAAATATGT 
                   
               
               
                   
                 CTTTTATTTCGT 
                   
               
               
                 Avian 
                 ACGAAAAAGAAGAATAAAAGGCAGAAGCCTTTTAAAAGGAACCCTGGG 
                 81 
               
               
                 paramyxovirus 
                 CTGTCGTAGGTGTGGGAAGGTTGTATTCCGAGTGCGCCTTCGAGGCATC 
                   
               
               
                 4 strain 
                 TACTCTACACCTATCACAATGGCTGGTGTCTTCTCCCAGTATGAGAGGTT 
                   
               
               
                 APMV4/duck/ 
                 TGTGGACAATCAATCCCAAGTGTCAAGGAAGGATCATCGTTCCCTGGCA 
                   
               
               
                 China/G302/ 
                 GGGGGATGCCTAAAAGTCAACATCCCTATGCTTGTCACTGCATCTGAAG 
                   
               
               
                 2012, 
                 ATCCCACCACTCGTTGGCAACTAGCATGTTTATCCTTAAGGCTCTTGGTC 
                   
               
               
                 complete 
                 TCCAACTCATCAACCAGTGCTATCCGCCAGGGGGCGATACTGACTCTCA 
                   
               
               
                 genome 
                 TGTCACTACCATCACAAAATATGAGAGCAACGGCAGCTATTGCTGGTTC 
                   
               
               
                 Genbank: 
                 CACAAATGCGGCTGTTATCAACACTATGGAAGTCTTGAGTGTCAACGAC 
                   
               
               
                 KC439346.1 
                 TGGACCCCATCCTTCGACCCCAGGAGCGGTCTCTCTGAAGAGGATGCTC 
                   
               
               
                   
                 AGGTTTTCAGAGACATGGCAAGGGACCTGCCCCCTCAGTTCACCTCCGG 
                   
               
               
                   
                 GTCACCCTTTACATCGGCATTGGCGGAGGGGTTTACCCCGGAGGACACC 
                   
               
               
                   
                 CACGACCTAATGGAGGCCCTGACCAGTGTGCTGATACAGATCTGGATCC 
                   
               
               
                   
                 TGGTGGCTAAGGCCATGACCAACATTGATGGCTCTGGGGAAGCCAATG 
                   
               
               
                   
                 AGAGACGTCTTGCAAAGTACATCCAGAAGGGACAGCTTAATCGCCAGTT 
                   
               
               
                   
                 TGCAATTGGTAATCCTGCTCGTCTGATAATCCAACAGACGATCAAAAGC 
                   
               
               
                   
                 TCCTTAACTGTCCGCAGGTTCTTGGTCTCTGAGCTTCGTGCATCACGAGG 
                   
               
               
                   
                 TGCGGTGAAAGAAGGATCCCCTTACTATGCGGCTGTTGGGGATATCCAC 
                   
               
               
                   
                 GCTTACATCTTTAACGCAGGACTGACACCATTCTTGACTACCTTAAGAT 
                   
               
               
                   
                 ACGGGATAGGCACCAAATATGCTGCTGTTGCACTCAGTGTGTTCGCTGC 
                   
               
               
                   
                 AGACATTGCAAAATTAAAGAGTCTACTTACCCTATACCAGGACAAGGGT 
                   
               
               
                   
                 GTGGAGGCCGGATACATGGCACTCCTCGAAGATCCAGACTCTATGCACT 
                   
               
               
                   
                 TTGCGCCTGGAAACTTCCCACACATGTACTCCTACGCGATGGGGGTGGC 
                   
               
               
                   
                 TTCTTACCATGACCCCAGCATGCGCCAGTACCAATATGCTAGGAGGTTC 
                   
               
               
                   
                 CTCAGCCGTCCTTTCTACTTGCTAGGGAGGGACATGGCTGCCAAGAACA 
                   
               
               
                   
                 CAGGCACGCTGGATGAGCAACTGGCAAAGGAACTACAAGTGTCAGAAA 
                   
               
               
                   
                 GAGACCGTGCCGCATTGTCCGCTGCGATTCAATCAGCAATGGAGGGGG 
                   
               
               
                   
                 GAGAATCTGACGACTTCCCACTATCGGGATCCATGCCGGCTCTCTCCGA 
                   
               
               
                   
                 CAATGCGCAACCAGTTACCCCAAGAACTCAACAGTCCCAGCTCTCCCCT 
                   
               
               
                   
                 CCCCAATCATCAAGCATGTCTCAATCAGCGCCCAGGACCCCGGACTACC 
                   
               
               
                   
                 AGCCTGATTTTGAACTGTAGGCTGCATCCACGCACCAACAGCAGGCCAA 
                   
               
               
                   
                 AGAAACCACCCCCCTCCTCACACATCCCACCCAATCACCCGCCAAGACC 
                   
               
               
                   
                 CAATCCAACACCCCAGCATCCCCCTCATTTAATTAAAAACTGACCAATA 
                   
               
               
                   
                 GGGTGGGGAAGGAGAGTTATTGGCTATTGCCAAGTTCGTGCAGCAATG 
                   
               
               
                   
                 GATTTTACCGATATTGATGCTGTCAACTCATTAATTGAATCATCATCAGC 
                   
               
               
                   
                 AATCATAGATTCCATACAGCATGGAGGGCTGCAACCATCAGGCACTGTC 
                   
               
               
                   
                 GGCCTATCACAAATCCCAAAGGGGATAACCAGCGCCTTAACCAAGGCC 
                   
               
               
                   
                 TGGGAGGCCGAGGCAGCAACTGCTGGCAACGGGGACACCCAACACAAA 
                   
               
               
                   
                 TCTGACAGTCCGGAAGACCATCAGGCCAACGACGCAGACTCCCCCGAA 
                   
               
               
                   
                 GACACAGGCACCAACCAGACCATCCAAGAAGCCAATATCGTTGAAACA 
                   
               
               
                   
                 CCCCACCCCGAAGTGCTATCGGCAGCCAAAGCCAGACTCAAGAGGCCC 
                   
               
               
                   
                 AAGACAGGGAGGGACACCCACGACAATCCCTCTGCGCAACCTGATCAT 
                   
               
               
                   
                 CTTTTAAAGGGGGGCCCCCTGAGCCCACAACCAGCGGCACCGTGGGTG 
                   
               
               
                   
                 AAAGATCCATCCATTCATGGAGGTCCCGGCACCGCCGATCCCCGCCCAT 
                   
               
               
                   
                 CACAAACTCAGGATCATTCCCTCACCGGAGAGAGATGGCAATCGTCACC 
                   
               
               
                   
                 GACAAAGCAACCGGAGACATCGAACTGGTGGAATGGTGCAACCCGGGG 
                   
               
               
                   
                 TGCACAGCTATCCGAGCTGAACCAACCAGACTCGACTGTGTATGCGGAC 
                   
               
               
                   
                 ACTGCCCCACCATCTGCAGCCTCTGCATGTATGACGACTGATCAGGTAC 
                   
               
               
                   
                 AACTATTAATGAAGGAGGTTGCCGACATGAAATCACTCCTTCAGGCACT 
                   
               
               
                   
                 AGTGAGGAACCTAGCTGTCCTGCCTCAACTAAGGAATGAGGTTGCAGCA 
                   
               
               
                   
                 ATCAGGACATCACAGGCCATGATAGAGGGGACACTCAATTCAATCAAG 
                   
               
               
                   
                 ATTCTCGACCCTGGGAATTATCAAGAATCATCACTAAACAGTTGGTTCA 
                   
               
               
                   
                 AACCACGCCAAGATCACGCGGTTGTTGTGTCCGGACCAGGGAATCCATT 
                   
               
               
                   
                 GGCCATGCCAACCCCGATCCAAGACAACACCATATTCCTAGATGAACTG 
                   
               
               
                   
                 GCAAGACCTCATCCTAGTTTGGTCAATCCGTCCCCGCCCGCTACCAACA 
                   
               
               
                   
                 CCAATGCTGATCTTGGCCCACAGAAGCAGGCTGCGATAGCTTATATCTC 
                   
               
               
                   
                 AGCAAAATGCAAGGATCAAGGGAAACGAGACCAGCTCTCAAAGCTCAT 
                   
               
               
                   
                 CGAGCGAGCAACCACCCTGAGCGAGATCAACAAAGTCAAAAGACAGGC 
                   
               
               
                   
                 CCTTGGCCTCTAGACCACTCGACCACCCCCAGTGATGAATACAACAATA 
                   
               
               
                   
                 ATCAGAACCTCCCTAAACCACATGGCCAACCCAGCGCACCATCCACACC 
                   
               
               
                   
                 ACCTATTACTACCCTTCGCCAGAAACTCCGCCGCAGCCGATTTATTCAA 
                   
               
               
                   
                 AAGAAGCCACTCGATATGACTTAGCAACCGCAAGATAGGGTGGGGAAG 
                   
               
               
                   
                 GTGCTTTACCTGCAAGAGGGCTCCCTCATCTTCAGACACGCACCCGCCA 
                   
               
               
                   
                 ACCCACCAGTGACGCAATGGCAGACATGGACACTGTATATATCAATCTG 
                   
               
               
                   
                 ATGGCAGATGATCCAACCCACCAAAAAGAACTGCTGTCCTTTCCCCTCA 
                   
               
               
                   
                 TTCCCGTGACTGGTCCTGACGGGAAAAAGGAACTCCAACACCAGGTCCG 
                   
               
               
                   
                 GACTCAATCCTTGCTCGCCTCAGACAAGCAAACTGAGAGGTTCATCTTC 
                   
               
               
                   
                 CTCAACACTTACGGGTTTATCTATGACACTACACCGGACAAGACAACTT 
                   
               
               
                   
                 TTTCTACCCCAGAGCATATCAATCAACCCAAGAGAACGATGGTGAGTGC 
                   
               
               
                   
                 TGCAATGATGACCATCGGCCTGGTCCCCGCCAATATACCCTTGAACGAA 
                   
               
               
                   
                 CTAACAGCTACTGTGTTTGGCCTGAAAATAAGAGTGAGGAAGAGTGCG 
                   
               
               
                   
                 AGATATCGAGAGGTGGTCTGGTACCAGTGCAACCCTGTACCAGCCCTGC 
                   
               
               
                   
                 TTGCAGCCACAAGGTTTGGTCGCCAAGGAGGTCTCGAATCGAGCACTGG 
                   
               
               
                   
                 AGTTAGTGTAAGGGCCCCCGAGAAGATAGACTGCGAGAAGGATTATAC 
                   
               
               
                   
                 TTACTACCCTTATTTCCTATCTGTGTGCTACATCGCCACTTCCAACCTGTT 
                   
               
               
                   
                 CAAGGTACCAAAAATGGTCGCTAATGCGACCAACAGTCAATTATACCAC 
                   
               
               
                   
                 CTGACCATGCAGATCACATTTGCCTTTCCAAAAAACATCCCCCCAGCTA 
                   
               
               
                   
                 ACCAGAAACTCCTGACACTAGTGGATGAAGGATTCGAGGGCACTGTGG 
                   
               
               
                   
                 ACTGCCATTTTGGGAACATGCTGAAAAAGGATCGGAAAGGGAACATGA 
                   
               
               
                   
                 GGACACTGTCGCAGGCGGCAGACAAGGTCAGACGGATGAACATCCTTG 
                   
               
               
                   
                 TTGGTATCTTTGACTTGCATGGGCCAACACTCTTCCTGGAGTACACCGG 
                   
               
               
                   
                 GAAGCTAACAAAAGCTCTGTTAGGGTTCATGTCTACCAGCCGAACAGCA 
                   
               
               
                   
                 ATCATCCCCATATCTCAGCTCAATCCTATGCTGAGTCAACTCATGTGGA 
                   
               
               
                   
                 GCAGTGATGCCCAGATAGTAAAATTAAGAGTGGTCATAACTACATCCAA 
                   
               
               
                   
                 ACGCGGCCCATGCGGGGGTGAGCAGGAGTATGTGCTGGATCCCAAATT 
                   
               
               
                   
                 CACTGTTAAAAAAGAGAAAGCCCGACTCAACCCTTTCAAGAAGGCAGC 
                   
               
               
                   
                 CCAATGATCAAATCTACAAGATCTCAGGAATCAGACCACTCTATACTAT 
                   
               
               
                   
                 CCACTGATCAATAGACATGTAGCTATACAGTTGATGAACCTATGAAGAA 
                   
               
               
                   
                 TCAGTTAGAAAACCGAATCCTTACTAGGGTGGGGAAGGAGTTGATTGG 
                   
               
               
                   
                 GTGTCTAAACAAAAACATTCCTTTACACCTCCTCGCCACGAAACAACCA 
                   
               
               
                   
                 TAATGAGGTTATCACGCACAATCCTGACCTTGATTCTCGGCACACTTACT 
                   
               
               
                   
                 GATTATTTAATGGGTGCTCACTCCACCAATGTAACTGAGAGACCAAAGT 
                   
               
               
                   
                 CTGAGGGGATTAGGGGTGATCTTACACCAGGCGCAGGTATCTTTGTAAC 
                   
               
               
                   
                 TCAAGTCCGACAACTACAGATCTACCAACAGTCTGGGTATCATGACCTT 
                   
               
               
                   
                 GTCATCAGATTATTACCTCTTCTACCGGCAGAACTCAATGATTGTCAAA 
                   
               
               
                   
                 GGGAAGTTGTCACAGAGTACAACAATACGGTATCACAGCTGTTGCAGCC 
                   
               
               
                   
                 TATCAAAACCAACCTGGATACCTTACTGGCTGGTGGTGGCACAAGGGAT 
                   
               
               
                   
                 GCCGATATACAGCCGCGGTTCATTGGGGCAATCATAGCCACAGGTGCCC 
                   
               
               
                   
                 TGGCGGTGGCTACGGTAGCTGAGGTGACTGCAGCCCAAGCACTATCTCA 
                   
               
               
                   
                 GTCGAAAACAAACGCTCAAAATATTCTCAAGTTGAGGGATAGTATTCAG 
                   
               
               
                   
                 GCCACCAACCAGGCAGTTTTCGAAATTTCACAAGGACTCGAGGCAACTG 
                   
               
               
                   
                 CAACTGTGCTATCAAAACTGCAAACTGAGCTCAATGAGAACATTATCCC 
                   
               
               
                   
                 AAGCCTGAACAACTTGTCCTGTGCTGCCATGGGTAATCGCCTTGGTGTA 
                   
               
               
                   
                 TCACTATCACTCTACTTGACCTTAATGACCACCCTATTTGGGGACCAGAT 
                   
               
               
                   
                 CACAAACCCAGTGCTGACACCGATCTCCTATAGCACTCTATCGGCAATG 
                   
               
               
                   
                 GCAGGTGGTCATATTGGCCCGGTAATGAGTAAAATATTAGCCGGATCTA 
                   
               
               
                   
                 TCACAAGTCAGTTGGGGGCGGAACAGTTGATTGCTAGCGGCTTAATACA 
                   
               
               
                   
                 GTCACAGGTAGTAGGTTATGATTCCCAATACCAATTATTGGTTATCAGG 
                   
               
               
                   
                 GTCAACCTTGTACGGATTCAAGAGGTCCAGAATACGAGAGTCGTATCAC 
                   
               
               
                   
                 TAAGAACACTAGCAGTCAATAGGGACGGTGGACTCTATAGAGCCCAGG 
                   
               
               
                   
                 TGCCTCCCGAGGTAGTTGAACGGTCTGGCATTGCAGAACGATTTTATGC 
                   
               
               
                   
                 AGATGATTGTGTTCTTACTACAACCGATTACATTTGCTCATCGATCCGAT 
                   
               
               
                   
                 CTTCTCGGCTTAATCCAGAGTTAGTTAGATGTCTCAGTGGGGCACTTGAT 
                   
               
               
                   
                 TCATGCACATTTGAGAGGGAAAGTGCATTATTGTCAACCCCTTTCTTTGT 
                   
               
               
                   
                 ATACAACAAGGCAGTTGTCGCAAATTGTAAAGCAGCAACATGTAGATG 
                   
               
               
                   
                 TAATAAACCGCCGTCTATTATTGCCCAATACTCTGCATCAGCTCTGGTCA 
                   
               
               
                   
                 CCATCACCACCGACACCTGTGCCGACCTCGAAATTGAGGGTTATCGCTT 
                   
               
               
                   
                 CAACATACAGACTGAATCCAACTCATGGGTTGCACCAAACTTCACTGTC 
                   
               
               
                   
                 TCGACTTCACAGATTGTATCAGTTGATCCCATAGACATCTCTTCTGACAT 
                   
               
               
                   
                 TGCCAAAATCAACAGTTCCATCGAGGCTGCAAGAGAGCAGCTGGAACT 
                   
               
               
                   
                 AAGCAACCAGATCCTTTCCCGGATCAACCCACGAATCGTGAATGATGAA 
                   
               
               
                   
                 TCACTGATAGCTATTATCGTGACAATTGTTGTGCTTAGTCCCCTCGTAAT 
                   
               
               
                   
                 CGGTCTGATTGTTGTTCTCGGTGTGATGTATAAGAATCTTAGGAAAGTC 
                   
               
               
                   
                 CAACGAGCTCAAGCTGCCATGATGATGCAGCAAATGAGCTCATCACAG 
                   
               
               
                   
                 CCTGTGACCACTAAATTAGGGACGCCTTTCTAGGAGAACAACCATATCA 
                   
               
               
                   
                 CTCCACTCAATGATGAGCAAGACGTACCAATCATCAATGATTGTGTCAC 
                   
               
               
                   
                 AAGGCCGGTTGGGAATGCATCGAATCTCTCCCCTTTCTTTTTAATTAAAA 
                   
               
               
                   
                 ACATTTGAAGTGAAGATGAGAGGGGGGAAGTGTATGGTAGGGTGGGGA 
                   
               
               
                   
                 AGGCAGCCAATTCCTGCCCATTAGGCCGACCGTATCAAAAGGATTCAAT 
                   
               
               
                   
                 AGAAGTCTAGGTACAGGGTAACATGGAGGGCAGCCGCGATAATCTTAC 
                   
               
               
                   
                 AGTGGATGATGAATTAAAGACAACATGGAGGTTAGCTTATAGAGTTGTG 
                   
               
               
                   
                 TCTCTTCTATTGATGGTGAGCGCTTTGATAATCTCTATAGTAATCCTGAC 
                   
               
               
                   
                 GAGAGATAACAGCCAAAGCATAATCACGGCGATCAACCAGTCATCTGA 
                   
               
               
                   
                 CGCAGACTCTAAGTGGCAAACGGGAATAGAAGGGAAAATCACCTCCAT 
                   
               
               
                   
                 TATGGCTGATACGCTCGATACCAGGAATGCAGTTCTTCTCCACATTCCA 
                   
               
               
                   
                 CTCCAGCTCAACACTCTTGAGGCGAACCTATTGTCTGCCCTTGGGGGCA 
                   
               
               
                   
                 ACACAGGAATTGGCCCCGGAGATCTAGAGCACTGCCGTTACCCTGTTCA 
                   
               
               
                   
                 TGACACCGCTTACCTGCATGGAGTTAATCGATTACTCATCAATCAGACA 
                   
               
               
                   
                 GCTGATTATACAGCAGAAGGCCCCCTAGATCATGTGAACTTCATTCCAG 
                   
               
               
                   
                 CCCCGGTTACGACTACTGGATGCACAAGGATACCATCCTTTTCCGTGTC 
                   
               
               
                   
                 ATCGTCCATTTGGTGCTATACACATAACGTGATTGAAACCGGTTGCAAT 
                   
               
               
                   
                 GACCACTCAGGTAGTAATCAATATATCAGCATGGGAGTCATTAAGAGA 
                   
               
               
                   
                 GCGGGCAACGGCCTACCTTACTTCTCAACAGTTGTAAGTAAGTATCTGA 
                   
               
               
                   
                 CTGATGGGTTGAATAGGAAAAGCTGTTCTGTGGCTGCCGGATCTGGGCA 
                   
               
               
                   
                 TTGCTACCTCCTTTGCAGCTTAGTGTCGGAGCCCGAACCTGATGACTATG 
                   
               
               
                   
                 TGTCACCTGATCCTACACCGATGAGGTTAGGGGTGCTAACGTGGGATGG 
                   
               
               
                   
                 ATCTTACACTGAACAGGTGGTACCCGAAAGAATATTCAGGAACATATGG 
                   
               
               
                   
                 AGTGCAAACTACCCAGGAGTAGGGTCAGGTGCTATAGTAGGAAATAAG 
                   
               
               
                   
                 GTGTTATTCCCATTTTACGGCGGAGTGAGGAATGGATCGACCCCGGAGG 
                   
               
               
                   
                 TGATGAATAGGGGAAGGTACTACTACATCCAGGATCCAAATGACTATTG 
                   
               
               
                   
                 CCCTGACCCGCTGCAAGATCAGATCTTAAGGGCGGAACAATCGTATTAC 
                   
               
               
                   
                 CCAACTCGATTCGGTAGGAGGATGATAATGCAGGGGGTCCTAGCATGTC 
                   
               
               
                   
                 CAGTATCCAACAATTCAACAATAGCAAGCCAATGTCAATCTTACTATTT 
                   
               
               
                   
                 TAATAACTCATTAGGGTTCATTGGAGCAGAATCTAGAATCTATTACCTC 
                   
               
               
                   
                 AATAGTAACATTTACCTTTATCAGAGGAGCTCGAGCTGGTGGCCTCACC 
                   
               
               
                   
                 CCCAGATTTACCTGCTTGATTCTAGGATTGCAAGTCCGGGTACTCAGAA 
                   
               
               
                   
                 CATTGACTCAGGTGTCAATCTCAAGATGTTAAACGTCACTGTGATTACA 
                   
               
               
                   
                 CGACCATCATCTGGTTTTTGTAATAGTCAGTCACGATGCCCTAATGACTG 
                   
               
               
                   
                 CTTATTCGGGGTCTACTCGGATATCTGGCCTCTTAGCCTTACCTCGGATA 
                   
               
               
                   
                 GCATATTCGCGTTCACTATGTATTTACAGGGGAAGACAACACGTATTGA 
                   
               
               
                   
                 CCCGGCTTGGGCGCTATTCTCCAATCATGCGATTGGGCATGAGGCTCGT 
                   
               
               
                   
                 CTGTTTAATAAGGAGGTTAGTGCTGCTTATTCTACCACCACTTGTTTTTT 
                   
               
               
                   
                 GGACACCATCCAAAACCAGGTGTATTGCCTGAGTATACTTGAGGTCAGG 
                   
               
               
                   
                 AGTGAGCTCTTGGGAGCATTCAAAATAGTACCATTCCTCTATCGTGTCTT 
                   
               
               
                   
                 GTAGGCATCCATTCGGCCAAAAAACTTGAGTGACTATGAGGTTAACACT 
                   
               
               
                   
                 TGATCCCCCTTAAAGACACCTATCTAAATTACTGTCCTAGACCCATGATT 
                   
               
               
                   
                 AGGTACCTTTTAAATCAATCATTTGGTTTTTAATTAAAAATGAAAAAAT 
                   
               
               
                   
                 GGGCCTAGTTTCAAGAGAGGGCTGGAACCCACTAGGGTGGGGAAGGAT 
                   
               
               
                   
                 TGCTTTGCTCCTTGACTCACACCCACGTATACTCGATCTCACTTCTGTAA 
                   
               
               
                   
                 AGAAGGGATCCTTCTCAAACTCGCCCCACAATGTCCAATCAGGCAGCTG 
                   
               
               
                   
                 AGATTATACTACCCACCTTCCATCTAGAATCACCCTTAATCGAGAATAA 
                   
               
               
                   
                 GTGCTTTTATTATATGCAATTACTTGGTCTCGTGTTGCCACATGATCATT 
                   
               
               
                   
                 GGAGATGGAGGGCATTCGTTAACTTTACAGTGGATCAGGTGCACCTTAA 
                   
               
               
                   
                 AAATCGTAATCCCCGCTTAATGGCCCATATCGACCACACTAAAGATAGA 
                   
               
               
                   
                 TTAAGGACTCATGGTGTCTTAGGTTTCCACCAGACTCAGACAAGTTTGA 
                   
               
               
                   
                 GCCGTTATCGTGTTTTGCTCCATCCTGAAACCTTACCTTGGCTATCAGCC 
                   
               
               
                   
                 ATGGGAGGATGCATCAATCAGGTTCCTAAAGCATGGCGGAATACTCTGA 
                   
               
               
                   
                 AATCGATCGAGCATAGTGTAAAGCAGGAGGCACCTCAACTAAAGCTAC 
                   
               
               
                   
                 TCATGGAGAGAACCTCATTAAAATTAACTGGAGTACCTTACTTGTTCTCT 
                   
               
               
                   
                 AATTGCAATCCCGGGAAAACCACAGCAGGAACTATGCCTGTCCTAAGTG 
                   
               
               
                   
                 AGATGGCATCGGAACTCTTGTCAAATCCTATCTCCCAATTCCAATCAAC 
                   
               
               
                   
                 ATGGGGGTGTGCTGCTTCGGGGTGGCACCATGTAGTCAGTATCATGAGG 
                   
               
               
                   
                 CTCCAACAATATCAAAGAAGGACAGGTAAGGAAGAGAAAGCAATCACC 
                   
               
               
                   
                 GAAGTTCAGTATGGCACAGACACTTGTCTCATTAACGCAGACTATACCG 
                   
               
               
                   
                 TTGTTTTTTCCACACAGAACCGTGTTATAACGGTCTTGCCCTTCGATGTT 
                   
               
               
                   
                 GTCCTCATGATGCAAGACCTACTCGAATCCCGACGGAATGTTCTGTTCT 
                   
               
               
                   
                 GTGCCCGCTTTATGTATCCCAGAAGCCAACTTCATGAGAGGATAAGTGC 
                   
               
               
                   
                 AATATTAGCCCTTGGAGACCAACTGGGGAGAAAAGCACCCCAAGTCCT 
                   
               
               
                   
                 GTATGATTTCGTGGCGACCCTCGAGTCATTTGCATACGCAGCTGTTCAA 
                   
               
               
                   
                 CTTCATGACAACAATCCTACCTACGGTGGGGCCTTCTTTGAATTCAATAT 
                   
               
               
                   
                 CCAAGAGTTAGAATCTATTCTGTCCCCTGCACTTAGTAAGGATCAGGTC 
                   
               
               
                   
                 AACTTCTACATAGGTCAAGTTGTCTCAGCGTACAGTAACCTTCCTCCATC 
                   
               
               
                   
                 TGAATCGGCAGAATTGTTGTGCCTGCTACGCCTGTGGGGTCATCCCTTG 
                   
               
               
                   
                 CTAAACAGCCTTGATGCAGCAAAGAAAGTCAGGGAGTCTATGTGTGCC 
                   
               
               
                   
                 GGGAAGGTTCTCGATTACAACGCCATTCGACTCGTCTTGTCTTTTTACCA 
                   
               
               
                   
                 TACATTGTTAATCAATGGGTACCGAAAGAAACACAAGGGTCGCTGGCC 
                   
               
               
                   
                 AAATGTGAATCAACATTCACTCCTCAACCCGATAGTGAGGCAGCTCTAT 
                   
               
               
                   
                 TTTGATCAGGAAGAGATCCCACACTCTGTTGCCCTTGAGCACTATTTGG 
                   
               
               
                   
                 ATGTCTCAATGATAGAATTTGAAAAAACTTTTGAAGTGGAACTATCTGA 
                   
               
               
                   
                 CAGCCTAAGCATCTTCCTGAAGGATAAGTCGATAGCTTTGGATAAGCAA 
                   
               
               
                   
                 GAATGGTACAGTGGTTTTGTCTCAGAAGTGACTCCGAAGCACCTACGAA 
                   
               
               
                   
                 TGTCTCGTCATGATCGCAAGTCTACCAATAGGCTCCTGTTAGCTTTCATT 
                   
               
               
                   
                 AACTCCCCTGAATTCGACGTTAAGGAGGAGCTTAAGTACTTGACTACGG 
                   
               
               
                   
                 GTGAGTACGCCACTGACCCAAATTTCAATGTCTCATACTCACTTAAAGA 
                   
               
               
                   
                 GAAGGAAGTAAAAAAAGAAGGGCGCATATTCGCAAAAATGTCACAAAA 
                   
               
               
                   
                 GATGAGAGCATGCCAGGTTATTTGTGAAGAATTGCTAGCACATCATGTG 
                   
               
               
                   
                 GCTCCTTTGTTTAAAGAGAATGGTGTTACTCAATCAGAGCTATCCCTGA 
                   
               
               
                   
                 CAAAAAATTTGTTGGCTATTAGCCAACTGAGTTACAACTCGATGGCTGC 
                   
               
               
                   
                 TAAGGTGCGATTGCTGAGGCCAGGGGACAAGTTCACTGCTGCACACTAT 
                   
               
               
                   
                 ATGACCACAGACCTAAAGAAGTACTGTCTCAATTGGCGGCACCAGTCAG 
                   
               
               
                   
                 TCAAACTGTTCGCCAGAAGCCTGGATCGACTGTTTGGATTAGACCATGC 
                   
               
               
                   
                 GTTTTCTTGGATACATGTCCGTCTCACCAACAGCACTATGTACGTTGCTG 
                   
               
               
                   
                 ACCCCTTCAATCCACCAGACTCAGAGGCATGCACAGATTTAGACGACAA 
                   
               
               
                   
                 TAAGAACACCGGGATTTTTATTATAAGTGCAAGAGGTGGTATAGAAGGC 
                   
               
               
                   
                 CTCCAACAAAAATTATGGACTGGCATATCGATTGCAATTGCCCAAGCGG 
                   
               
               
                   
                 CAGCGGCCCTCGAAGGCTTACGAATTGCTGCTACTCTGCAGGGGGATAA 
                   
               
               
                   
                 CCAAGTTTTGGCGATTACGAAGGAATTCATGACCCCAGTCCCAGAGGAT 
                   
               
               
                   
                 GTAATCCATGAGCAGCTATCTGAGGCGATGTCTCGATACAAAAGGACTT 
                   
               
               
                   
                 TCACATACCTCAATTATTTAATGGGGCATCAGTTGAAGGATAAAGAAAC 
                   
               
               
                   
                 CATCCAATCCAGTGACTTCTTTGTTTATTCCAAAAGAATCTTCTTCAATG 
                   
               
               
                   
                 GATCGATCTTAAGTCAATGCCTCAAAAACTTCAGTAAACTCACTACTAA 
                   
               
               
                   
                 TGCCACTACCCTTGCTGAGAATACTGTGGCCGGCTGCAGTGACATCTCT 
                   
               
               
                   
                 TCATGCATTGCCCGTTGTGTGGAAAACGGGTTGCCTAAGGATGCCGCAT 
                   
               
               
                   
                 ATATCCAGAATATAATCATGACTCGGCTTCAACTATTGCTAGATCATTA 
                   
               
               
                   
                 CTATTCAATGCATGGCGGCATAAATTCAGAATTAGAGCAGCCAACTTTA 
                   
               
               
                   
                 AGTATCTCTGTTCGAAACGCAACCTACTTACCATCTCAACTAGGCGGTT 
                   
               
               
                   
                 ACAATCATTTGAATATGACCCGACTATTCTGCCGCAATATCGGCGACCC 
                   
               
               
                   
                 GCTTACCAGTTCTTGGGCGGAGTCAAAAAGACTAATGGATGTTGGTCTC 
                   
               
               
                   
                 CTCAGTCGTAAGTTCTTAGAGGGGATATTATGGAGACCCCCGGGAAGTG 
                   
               
               
                   
                 GGACGTTTTCAACACTCATGCTTGACCCGTTCGCACTTAACATTGATTAC 
                   
               
               
                   
                 CTGAGGCCGCCAGAGACAATTATCCGAAAACACACCCAAAAAGTCTTG 
                   
               
               
                   
                 TTGCAAGATTGCCCAAATCCCCTATTAGCAGGTGTCGTTGACCCGAACT 
                   
               
               
                   
                 ACAACCAAGAATTAGAGCTGTTAGCTCAGTTCTTGCTTGATCGGGAAAC 
                   
               
               
                   
                 CGTTATTCCCAGGGCTGCCCATGCCATCTTCGAGTTATCTGTCTTGGGAA 
                   
               
               
                   
                 GGAAAAAACATATACAAGGATTGGTAGATACTACAAAGACAATTATTC 
                   
               
               
                   
                 AGTGCTCATTGGAAAGACAGCCATTGTCTTGGAGGAAAGTTGAGAACAT 
                   
               
               
                   
                 TGTTACCTACAACGCGCAGTATTTCCTCGGGGCCACCCAACAGGCTGAT 
                   
               
               
                   
                 ACTAATGTCTCAGAAGGGCAGTGGGTGATGCCAGGTAACCTTAAGAAG 
                   
               
               
                   
                 CTTGTGTCCCTCGACGATTGCTCGGTCACGCTGTCTACTGTATCACGGCG 
                   
               
               
                   
                 CATATCATGGGCCAATCTACTGAACTGGAGAGCTATAGATGGTCTGGAA 
                   
               
               
                   
                 ACCCCGGATGTGATAGAGAGTATTGATGGTCGCCTTGTACAATCATCCA 
                   
               
               
                   
                 ATCAATGTGGCCTATGTAATCAAGGGTTGGGATCCTACTCCTGGTTTTTC 
                   
               
               
                   
                 TTGCCCTCTGGGTGTGTGTTCGACCGTCCACAAGATTCTCGGGTAGTTCC 
                   
               
               
                   
                 AAAGATGCCATACGTGGGGTCCAAAACAGATGAGAGACAGACTGCATC 
                   
               
               
                   
                 AGTGCAAGCTATACAAGGATCCACTTGTCACCTCAGGGCAGCATTGAGG 
                   
               
               
                   
                 CTTGTATCACTCTACCTATGGGCCTATGGAGATTCTGACATATCATGGCT 
                   
               
               
                   
                 AGAAGCTGCAACGCTGGCTCAAACACGGTGCAATGTCTCTCTCGATGAT 
                   
               
               
                   
                 TTGCGAATCTTGAGCCCTCTTCCTTCTTCGGCGAATTTACACCACAGATT 
                   
               
               
                   
                 AAATGACGGGGTAACACAGGTTAAATTCATGCCCGCCACATCTAGCCGA 
                   
               
               
                   
                 GTGTCAAAGTTCGTCCAAATTTGCAATGACAACCAGAATCTTATCCGTG 
                   
               
               
                   
                 ATGATGGGAGTGTTGATTCCAATATGATTTATCAACAGGTTATGATATT 
                   
               
               
                   
                 AGGGCTTGGAGAGATTGAATGCTTGTTAGCTGACCCAATTGATACAAAC 
                   
               
               
                   
                 CCAGAACAATTGATTCTTCATCTACACTCTGATAATTCTTGCTGTCTCCG 
                   
               
               
                   
                 GGAGATGCCAACGACCGGCTTTGTACCTGCTCTAGGACTAACCCCATGT 
                   
               
               
                   
                 TTAACTGTCCCAAAGCATAATCCTTACATTTATGACGATAGCCCAATAC 
                   
               
               
                   
                 CCGGTGATTTGGATCAGAGGCTCATTCAGACCAAATTTTTCATGGGGTC 
                   
               
               
                   
                 TGACAATTTGGATAATCTTGATATCTACCAGCAGCGAGCTTTACTGAGT 
                   
               
               
                   
                 AGGTGTGTAGCTTATGATGTCATCCAATCGATCTTTGCCTGTGATGCACC 
                   
               
               
                   
                 AGTCTCTCAGAAGAATGACGCAATCCTTCACACTGATTACCATGAGAAT 
                   
               
               
                   
                 TGGATCTCAGAGTTCCGATGGGGTGACCCTCGTATTATCCAAGTAACGG 
                   
               
               
                   
                 CAGGCTATGAGTTAATTCTGTTCCTTGCATACCAGCTTTATTATCTCAGA 
                   
               
               
                   
                 GTGAGGGGTGACCGTGCAATCCTGTGCTATATCGACAGGATACTCAATA 
                   
               
               
                   
                 GGATGGTATCTTCCAATCTAGGTAGTCTCATCCAGACACTCTCTCATCCA 
                   
               
               
                   
                 GAGATTAGGAGGAGATTCTCGTTGAGTGATCAAGGGTTTCTTGTTGAAA 
                   
               
               
                   
                 GAGAACTAGAGCCAGGTAAGCCCTTGGTTAAACAAGCGGTTATGTTCTT 
                   
               
               
                   
                 AAGGGACTCGGTCCGCTGCGCTTTAGCAACTATCAAGGCAGGAATTGAG 
                   
               
               
                   
                 CCTGAAATCTCCCGAGGTGGTTGTACTCAGGATGAGCTGAGCTTTACTC 
                   
               
               
                   
                 TTAAGCACTTACTATGTCGGCGTCTCTGTGTAATCGCTCTCATGCATTCA 
                   
               
               
                   
                 GAAGCAAAGAACTTGGTTAAAGTTAGAAACCTTCCTGTAGAAGAGAAA 
                   
               
               
                   
                 ACCGCCTTATTGTACCAGATGTTGGTCACTGAGGCCAATGCTAGGAAAT 
                   
               
               
                   
                 CAGGGTCTGCCAGCATTATCATAAACCTAGTCTCGGCACCCCAGTGGGA 
                   
               
               
                   
                 CATTCATACACCAGCATTGTATTTTGTGTCAAAGAAAATGCTAGGGATG 
                   
               
               
                   
                 CTTAAGAGGTCAACCACACCCTTGGATATAAGTGACCTCTCTGAGAACC 
                   
               
               
                   
                 AGAACCCCGCACCTGCAGAGCTTAGTGATGCTCCTGGTCACATGGCAGA 
                   
               
               
                   
                 AGAATTCCCCTGTTTGTTTAGTAGTTATAACGCTACATATGAAGACACA 
                   
               
               
                   
                 ATCACTTACAATCCAATGACTGAAAAACTCGCCTTGCATTTGGACAACA 
                   
               
               
                   
                 GTTCCACCCCATCCAGAGCACTTGGTCGTCACTACATCCTGCGGCCTCTT 
                   
               
               
                   
                 GGGCTTTACTCATCCGCATGGTACCGGTCTGCGGCACTACTAGCGTCAG 
                   
               
               
                   
                 GGGCCCTAAATGGGTTGCCTGAGGGGTCGAGCCTGTATTTAGGAGAAG 
                   
               
               
                   
                 GGTACGGGACCACCATGACTCTGCTTGAGCCCGTTGTCAAGTCTTCAAC 
                   
               
               
                   
                 TGTTTACTACCATACATTGTTTGACCCAACCCGGAACCCTTCACAGCGG 
                   
               
               
                   
                 AACTATAAACCAGAACCACGGGTATTCACGGATTCTATTTGGTACAAGG 
                   
               
               
                   
                 ATGATTTCACACGGCCACCCGGTGGTATTATCAACCTGTGGGGTGAAGA 
                   
               
               
                   
                 TATACGTCAGAGTGATATCACACAGAAAGACACGGTCAACTTCATACTA 
                   
               
               
                   
                 TCTCAGATCCCGCCAAAATCACTTAAGTTGATACACGTTGATATTGAGT 
                   
               
               
                   
                 TCTCACCAGACTCCGATGTACGGACACTACTATCCGGCTATTCTCATTGT 
                   
               
               
                   
                 GCACTATTGGCCTACTGGCTATTGCAACCTGGAGGGCGATTCGCAGTTA 
                   
               
               
                   
                 GGGTTTTCTTAAGTGACCATATCATAGTTAACTTGGTCACTGCGATCCTG 
                   
               
               
                   
                 TCTGCTTTTGACTCCAATTTGGTGTGCATTGCGTCAGGATTGACACACAA 
                   
               
               
                   
                 GGATGATGGGGCAGGTTATATTTGCGCGAAAAAGCTTGCAAATGTTGAG 
                   
               
               
                   
                 GCTTCAAGAATTGAGTACTACTTGAGGATGGTCCATGGTTGTGTTGACT 
                   
               
               
                   
                 CATTAAAGATCCCTCATCAATTAGGAATCATTAAATGGGCCGAGGGTGA 
                   
               
               
                   
                 GGTGTCCCAGCTTACCAGAAAGGCGGATGATGAAATAAATTGGCGGTT 
                   
               
               
                   
                 AGGTGATCCAGTTACCAGATCATTTGATCCAGTTTCTGAGCTAATAATT 
                   
               
               
                   
                 GCACGAACAGGGGGGTCTGTATTAATGGAATACGGGGCTTTTACTAACC 
                   
               
               
                   
                 TCAGGTGTGCGAACTTGGTAGATACATACAAACTTCTGGCTTCAATTGT 
                   
               
               
                   
                 AGAGACCACCCTAATGGAAATAAGGGTTGAGCAAGATCAGTTGGAAGA 
                   
               
               
                   
                 TAGTTCGAGGAGACAAATCCAAGTAATCCCCGCTTTCAACACAAGATCT 
                   
               
               
                   
                 GGGGGAAGGATCCGTACACTGATTGAGTGTGCTCAGCTGCAGATTATAG 
                   
               
               
                   
                 ATGTTATTTGTGTAAACATAGATCACCTCTTTCCTAAACACCGACATGTT 
                   
               
               
                   
                 CTTGTCACACAACTTACCTACCAGTCGGTGTGCCTTGGGGATTTGATTGA 
                   
               
               
                   
                 AGGTCCCCAAATTAAGACGTATCTAAGGGCCAGAAAGTGGATCCAACG 
                   
               
               
                   
                 TCGGGGACTCAATGAGACAGTTAACCATATCATCACTGGACAAGTGTCA 
                   
               
               
                   
                 CGGAATAAAGCAAGGGATTTTTTTAAGAGGCGCCTGAAGTTGGTTGGCT 
                   
               
               
                   
                 TTTCACTCTGCGGAGGTTGGAGCTACCTCTCACTTTAGCTGTTCAGGTTG 
                   
               
               
                   
                 CTGATCATCATGAACAATCGGAGTCGGAATCGTAAACAGAAAGTCACA 
                   
               
               
                   
                 AAATTGTGGATAAACAATGATTGCATTAGTATTTAATAAAAAATATGTC 
                   
               
               
                   
                 TTTTATTTCGT 
                   
               
               
                 Avian 
                 ACGAAAAAGAAGAATAAAAGGCAGAAGCCTTTTAAAAGGAACCCTGGG 
                 82 
               
               
                 paramyxovirus 
                 CTGTCGTAGGTGTGGGAAGGTTGTATTCCGAGTGCGCCTCCGAGGCATC 
                   
               
               
                 4 strain 
                 TACTCTACACCTATCACAATGGCTGGTGTCTTTTCCCAGTATGAGAGGTT 
                   
               
               
                 APMV- 
                 TGTGGACAATCAATCTCAGGTGTCAAGGAAGGATCATCGGTCCTTAGCA 
                   
               
               
                 4/duck/Dela- 
                 GGAGGGTGCCTTAAAGTGAACATCCCTATGCTTGTCACTGCATCCGAAG 
                   
               
               
                 ware/549227 
                 ACCCCACCACGCGTTGGCAACTAGCATGCTTATCTCTGAGGCTCTTGATT 
                   
               
               
                 /2010, 
                 TCCAATTCATCAACCAGTGCTATCCGCCAGGGAGCAATACTGACCCTCA 
                   
               
               
                 complete 
                 TGTCATTGCCATCGCAAAACATGAGAGCAACAGCAGCTATTGCTGGGTC 
                   
               
               
                 genome 
                 CACGAATGCGGCTGTTATCAACACTATGGAAGTCTTAAGTGTCAATGAC 
                   
               
               
                 Genbank: 
                 TGGACCCCATCTTTTGACCCAAGAAGTGGTCTATCTGAGGAGGACGCTC 
                   
               
               
                 JX987283.1 
                 AGGTGTTCAGAGACATGGCAAGAGATCTGCCTCCTCAGTTCACTTCTGG 
                   
               
               
                   
                 ATCACCCTTTACATCAGCATTGGCGGAGGGGTTTACTCCCGAGGACACT 
                   
               
               
                   
                 CATGACCTGATGGAGGCACTGACTAGTGTACTGATACAGATCTGGATTC 
                   
               
               
                   
                 TGGTGGCCAAGGCCATGACCAATATTGATGGATCTGGGGAGGCTAACG 
                   
               
               
                   
                 AAAGACGCCTTGCAAAATACATCCAAAAGGGACAGCTCAATCGTCAGT 
                   
               
               
                   
                 TTGCAATTGGCAATCCTGCCCGTCTGATAATCCAACAGACAATCAAAAG 
                   
               
               
                   
                 CTCATTAACTGTCCGCAGGTTCTTGGTCTCTGAGCTCCGCGCATCACGTG 
                   
               
               
                   
                 GTGCAGTAAAGGAGGGTTCCCCTTACTATGCAGCCGTTGGGGATATCCA 
                   
               
               
                   
                 CGCTTACATCTTCAATGCAGGATTGACACCATTCTTGACCACCCTGAGA 
                   
               
               
                   
                 TATGGCATTGGCACCAAGTACGCCGCTGTCGCACTCAGTGTGTTTGCTG 
                   
               
               
                   
                 CAGACATTGCAAAATTGAAGAGTCTACTCACCCTGTATCAAGACAAAGG 
                   
               
               
                   
                 TGTAGAAGCTGGATACATGGCACTCCTTGAAGATCCAGATTCCATGCAC 
                   
               
               
                   
                 TTTGCACCTGGAAACTTCCCACACATGTATTCCTATGCGATGGGAGTGG 
                   
               
               
                   
                 CCTCCTATCACGACCCTAGCATGCGCCAATACCAGTATGCCAGGAGGTT 
                   
               
               
                   
                 TCTCAGTCGTCCCTTCTACCTGCTAGGAAGAGACATGGCTGCTAAGAAC 
                   
               
               
                   
                 ACAGGAACTCTGGATGAGCAGCTGGCGAAAGAACTGCAAGTGTCAGAG 
                   
               
               
                   
                 AGGGACCGCGCTGCACTGTCTGCCGCGATTCAATCAGCAATGGAGGGG 
                   
               
               
                   
                 GGAGAGTCAGATGACTTCCCATTGTCAGGATCCATGCCGGCCCTCTCTG 
                   
               
               
                   
                 AGAGCACACAACCGGTCACCCCCAGGACTCAACAGTCCCAGCTCTCTCC 
                   
               
               
                   
                 TCCTCAATCATCAAACATGTCCCAATCGGCGCCTAGGACCCCGGACTAT 
                   
               
               
                   
                 CAACCCGACTTTGAGCTGTAGACTATATCCACACACCGACAATAGCTCC 
                   
               
               
                   
                 AGAAGACCCCCTTCCCCCCCATACACCCCACCCGGTCATCCACAAAGAC 
                   
               
               
                   
                 CCAGTCCAACATCCCAGCACTATTCCCTTTTAATTAAAAACTGGCCGAC 
                   
               
               
                   
                 AGGGTGGGGAAGGAGGACTGTTAGCTGCCACCAACGGTGTGCAGCAAT 
                   
               
               
                   
                 GGATTTTACAGACATTGACGCTGTCAACTCACTGATTGAGTCATCATCG 
                   
               
               
                   
                 GCAATTATAGACTCCATACAGCATGGAGGGCTGCAACCAGCAGGCACT 
                   
               
               
                   
                 GTTGGCTTATCTCAAATTCCAAAAGGGATAACCAGTGCACTGAATAAAG 
                   
               
               
                   
                 CCTGGGAAGCTGAGGCGGCAACTGCCGGCAGTGGAGACACCCAACACA 
                   
               
               
                   
                 AACCCGATGACCCAGAGGACCACCAGGCTAGGGACACGGAGTCCCTGG 
                   
               
               
                   
                 AAGACACAGGCAACGACCCGGCCACACAGGGGACTAACATTGTTGAGA 
                   
               
               
                   
                 CACCCCACCCAGAAGTACTGTCAGCAGCCAAAGCTAGACTCAAGAGAC 
                   
               
               
                   
                 CCAAAGCAGGGAAAGACACCCATGGCAATCCCCCCACTCAACCCGATC 
                   
               
               
                   
                 ACTTTTTAAAGGGGGGCCTCCCGAGTCCACAACCGACAGCACCGCGGAT 
                   
               
               
                   
                 GCAAAGTCCACCCAACCATGGAAGCTCCAGCACCGCCGATCCCCGCCA 
                   
               
               
                   
                 ATCACAAACTCAGGATCATTCCCCCACCGGAGAGAAATGGCAATTGTCA 
                   
               
               
                   
                 CCGACAAAGCAACCGGAGACATCGAACTGGTGGAGTGGTGCAACCCAG 
                   
               
               
                   
                 GGTGTACAGCAGTCCGAATTGAACCAGCCAGACTTGACTGTGTATGCGG 
                   
               
               
                   
                 ACACTGCCCCACCATCTGCAGTCTCTGCATGTATGACGACTGATCAGGT 
                   
               
               
                   
                 ACAGTTGTTGATGAAGGAGGTTGCTGACATAAAATCACTCCTCCAGGCA 
                   
               
               
                   
                 CTAGTAAGGAATCTAGCTGTCTTGCCCCAACTAAGGAATGAGGTTGCAG 
                   
               
               
                   
                 CAATCAGAACATCACAGGCCATGATAGAGGGGACACTCAATTCAATTA 
                   
               
               
                   
                 AGATTCTTGATCCTGGAAATTATCAGGAATCATCACTAAACAGTTGGTT 
                   
               
               
                   
                 CAAACCTCGCCAGGAACACACTGTTATTGTGTCAGGACCAGGGAATCCA 
                   
               
               
                   
                 CTGGCCATGCCGACTCCAGTTCAGGACAGTACCATATTCTTAGATGAGC 
                   
               
               
                   
                 TAGCAAGACCTCATCCTAATTTGGTCAATCCGTCTCCGCCCGTCACCAG 
                   
               
               
                   
                 CACCAATGTTGACCTTGGCCCACAGAAGCAGGCTGCAATAGCCTACGTT 
                   
               
               
                   
                 TCCGCCAAGTGCAAGGACCCAGGGAAACGGGACCAGCTTTCAAGGCTT 
                   
               
               
                   
                 ATTGAACGGGCGGCTACCTTGAGTGAGATCAACAAGGTTAAAAGACAG 
                   
               
               
                   
                 GCTCTCGGGCTCTAAATTAATCAACCACCCGTTGCAACGATCGAGACAA 
                   
               
               
                   
                 CAATAAAAATCCCCCTGAATCACATGACCAAATCTGCATACCACTCACA 
                   
               
               
                   
                 TCATCCGCCTATACCCCTCACCATAAATACCACCTTAGCCGATTTATTTA 
                   
               
               
                   
                 AAAGAAATCATTCATCACAACCTGGTAATCATAAACTAGGGTGGGGAA 
                   
               
               
                   
                 GGTCTCTTGTCTGCAGGAAGGCTCCTCTGTCTCCAGGCACGCACCCGTC 
                   
               
               
                   
                 AACCCACCAATAACACAATGGCGGACATGGACACGATATACATCAACT 
                   
               
               
                   
                 TGATGGCAGATGATCCAACCCATCAAAAAGAATTGCTGTCATTCCCTCT 
                   
               
               
                   
                 GATTCCAGTGACTGGACCTGATGGGAAGAAAGTGCTCCAACACCAGAT 
                   
               
               
                   
                 CCGGACCCAATCCTTGCTCACCTCAGACAAACAAACGGAGAGGTTCATC 
                   
               
               
                   
                 TTTCTCAACACTTACGGGTTCATCTATGACACAACCCCGGACAAGACAA 
                   
               
               
                   
                 CTTTTTCCACCCCTGAGCATATCAATCAGCCTAAGAGGACAATGGTGAG 
                   
               
               
                   
                 TGCTGCGATGATGACTATTGGTCTGGTTCCTGCTACAATACCCCTGAATG 
                   
               
               
                   
                 AATTGACGGCCACTGTGTTTAACCTTAAAGTAAGAGTGAGGAAAAGTGC 
                   
               
               
                   
                 GAGGTATCGAGAAGTGGTTTGGTACCAGTGCAACCCCGTACCAGCTCTG 
                   
               
               
                   
                 CTCGCAGCCACCAGATTTGGCCGCCAAGGGGGTCTTGAGTCGAGCACCG 
                   
               
               
                   
                 GAGTCAGTGTAAAGGCACCTGAGAAGATTGATTGTGAGAAAGATTATA 
                   
               
               
                   
                 CTTACTACCCTTATTTCCTATCTGTGTGCTACATCGCCACTTCCAACCTCT 
                   
               
               
                   
                 TTAAGGTACCGAAGATGGTTGCCAATGCAACCAACAGTCAATTGTATCA 
                   
               
               
                   
                 CCTAACCATGCAGGTCACATTTGCATTTCCGAAAAACATTCCCCCAGCC 
                   
               
               
                   
                 AATCAGAAACTCCTGACACAGGTAGATGAAGGATTTGAGGGTACCGTG 
                   
               
               
                   
                 GATTGCCATTTTGGGAACATGCTAAAAAAGGATAGGAAAGGGAACATG 
                   
               
               
                   
                 AGGACTTTGTCTCAAGCAGCAGATAAGGTCAGAAGAATGAATATCCTTG 
                   
               
               
                   
                 TGGGAATATTTGACTTGCACGGACCTACACTATTCCTGGAATATACTGG 
                   
               
               
                   
                 GAAATTGACAAAAGCCCTGTTGGGGTTCATGTCCACCAGCCGAACAGCA 
                   
               
               
                   
                 ATCATCCCCATATCACAACTCAATCCTATGCTGAGTCAACTCATGTGGA 
                   
               
               
                   
                 GCAGTGACGCCCAGATAGTAAAGTTACGGGTGGTCATCACTACATCTAA 
                   
               
               
                   
                 ACGTGGCCCGTGTGGGGGCGAGCAGGAATATGTGCTGGATCCTAAATTC 
                   
               
               
                   
                 ACAGTTAAGAAAGAAAAGGCTCGACTCAATCCATTCAAGAAGGCAGCC 
                   
               
               
                   
                 TAATAATTAAACCTACAAGATCCCAAGAATTAAACAGCTCTATACAATT 
                   
               
               
                   
                 CATAGGTTGATAGAAATGCCACTACACAGCTAATGATTTTCCAGAAAAT 
                   
               
               
                   
                 CACTTAGAAAACCAAATCCTTATTAGGGTGGGGAAGTAGTTGATTGGGT 
                   
               
               
                   
                 GTCTAAACAAAAGTGCTTCTTTGCAACTCCCCACCCCGAAGCAATCACA 
                   
               
               
                   
                 ATGAGACCATTAAACACGCTTTTGACCGTGATTCTTATCATACTCATCAG 
                   
               
               
                   
                 CTATTTGGTGATTGTTCATTCTAGTGATGCGGTTGAGAGGCCAAGGACT 
                   
               
               
                   
                 GAGGGAATTAGGGGCGACCTCATTCCAGGTGCGGGTATCTTCGTGACTC 
                   
               
               
                   
                 AAGTCCGACAACTGCAAATCTATCAGCAGTCAGGGTACCACGACCTTGT 
                   
               
               
                   
                 CATAAGATTATTACCCCTTTTACCAACGGAACTCAATGATTGCCAAAAA 
                   
               
               
                   
                 GAAGTAGTCACAGAATACAATAATACAGTATCACAATTGTTGCAGCCTA 
                   
               
               
                   
                 TCAAAACCAACTTGGATACCCTATTAGCAGATGGTAATACGAGGGAAG 
                   
               
               
                   
                 CGGATATACAGCCGCGGTTTATTGGAGCAATAATAGCCACAGGTGCCTT 
                   
               
               
                   
                 GGCGGTAGCAACAGTGGCAGAAGTAACTGCAGCTCAGGCACTCTCCCA 
                   
               
               
                   
                 GTCCAAAACAAATGCTCAAAATATTCTCAAGCTAAGAGATAGTATCCAG 
                   
               
               
                   
                 GCCACCAACCAAGCGGTCTTTGAAATTTCACAAGGGCTTGAGGCAACTG 
                   
               
               
                   
                 CAACTGTGCTATCGAAACTACAGACAGAGCTCAATGAGAATATTATCCC 
                   
               
               
                   
                 AAGCCTGAACAATTTATCCTGTGCTGCCATGGGGAATCGTCTTGGTGTA 
                   
               
               
                   
                 TCACTCTCACTCTATTTAACTCTAATGACTACCCTCTTTGGGGACCAAAT 
                   
               
               
                   
                 TACGAACCCAGTGCTGACACCAATTTCTTACAGCACACTATCGGCAATG 
                   
               
               
                   
                 GCAGGTGGTCATATTGGCCCAGTGATGAGTAAAATATTAGCCGGATCGG 
                   
               
               
                   
                 TCACGAGCCAGTTGGGGGCAGAACAATTGATTGCTAGTGGCTTAATACA 
                   
               
               
                   
                 ATCACAGGTGGTAGGCTATGATTCCCAGTATCAATTATTGGTAATCAGG 
                   
               
               
                   
                 GTTAACCTTGTTCGGATTCAGGAAGTCCAGAATACCAGGGTTGTATCAT 
                   
               
               
                   
                 TAAGAACGCTAGCTGTCAATAGAGATGGTGGACTTTATAGAGCCCAAGT 
                   
               
               
                   
                 TCCACCTGAGGTAGTCGAACGATCCGGCATTGCAGAGCGGTTTTACGCA 
                   
               
               
                   
                 GATGATTGTGTTCTCACCACGACCGACTATATTTGCTCATCAATCAGATC 
                   
               
               
                   
                 CTCTCGGCTTAATCCAGAATTAGTCAAGTGTCTCAGTGGGGCACTTGAT 
                   
               
               
                   
                 TCATGTACATTCGAGAGGGAGAGTGCCCTGTTATCAACTCCTTTCTTTGT 
                   
               
               
                   
                 GTACAATAAGGCTGTCGTAGCAAATTGCAAAGCGGCAACATGCAGATG 
                   
               
               
                   
                 CAACAAACCACCGTCAATTATTGCTCAATATTCTGCATCAGCTCTAGTA 
                   
               
               
                   
                 ACCATCACCACTGACACCTGTGCCGATCTCGAAATTGAGGGTTACCGTT 
                   
               
               
                   
                 TCAACATACAGACTGAATCTAACTCGTGGGTTGCACCTAACTTTACTGT 
                   
               
               
                   
                 CTCAACCTCACAGATAGTGTCAGTTGATCCAATAGACATATCCTCTGAC 
                   
               
               
                   
                 ATCGCAAAAATCAACAATTCGATTGAGGCCGCACGAGAGCAGCTAGAA 
                   
               
               
                   
                 CTGAGCAACCAGATCCTATCCCGGATTAACCCCCGAATCGTGAATGACG 
                   
               
               
                   
                 AATCACTGATAGCTATTATCGTGACAATTGTTGTGCTTAGTCTCCTTGTA 
                   
               
               
                   
                 GTCGGTCTTATCATTGTTCTCGGCGTGATGTATAAAAATCTCAAGAAGG 
                   
               
               
                   
                 TCCAACGAGCTCAGGCTGCTATGATGATGCAGCAAATGAGTTCATCGCA 
                   
               
               
                   
                 GCCTGTAACCACAAAACTGGGGACACCCTTCTAGGTGAATAAATGCATC 
                   
               
               
                   
                 ACCTCTTTCCTTGATGAGCGAGATGTCTTAATCATTGATAATTATGCCGT 
                   
               
               
                   
                 AAGGCTGGTAGGGAATGTGCTGAATCTCTCCTCTTCCTTTTTAATTAAAA 
                   
               
               
                   
                 ACGGTTGAACTGAGGGGGAGAATGTGCATGGTAGGGTGGGGAAGGTGT 
                   
               
               
                   
                 CTGATTCCTACCTATCGGGCCAACTGTACCAGTAGAAGCTAACAGGAAT 
                   
               
               
                   
                 TCTAATGCAGAGTGACATGGAGGGCAGTCGTGATAACCTCACAGTGGAT 
                   
               
               
                   
                 GATGAGTTAAAGACAACATGGAGGTTAGCTTACAGAGTTGTATCTCTCC 
                   
               
               
                   
                 TATTAATGGTGAGTGCTTTGATAATTTCTATAGTAATCTTGACGAGGGAT 
                   
               
               
                   
                 AACAGCCAAAGCATAATCACGGCAATCAACCAGTCATATGATGCAGAC 
                   
               
               
                   
                 TCAAAGTGGCAAACAGGGATAGAGGGGAAAATCACCTCTATCATGACT 
                   
               
               
                   
                 GATACGCTTGATACTAGGAATGCAGCTCTCCTCCACATTCCACTCCAAC 
                   
               
               
                   
                 TTAATACACTTGAAGCAAACCTATTATCAGCCCTCGGTGGCAACACAGG 
                   
               
               
                   
                 AATCGGCCCCGGGGATCTAGAGCATTGCCGTTATCCAGTTCATGATTCT 
                   
               
               
                   
                 GCTTACCTGCATGGAGTCAACCGATTACTTATCAATCAAACGGCTGATT 
                   
               
               
                   
                 ATACAGCAGAGGGTCCACTAGATCATGTGAACTTCATACCGGCACCAGT 
                   
               
               
                   
                 TACGACCACTGGATGCACTAGGATACCATCTTTTTCCGTGTCCTCATCCA 
                   
               
               
                   
                 TTTGGTGTTATACTCACAATGTGATTGAAACTGGTTTTAATGATCACTCA 
                   
               
               
                   
                 GGCAGCAATCAGTATATTAGCATGGGGGTGATTAAGAGGGCTGGCAAC 
                   
               
               
                   
                 GGCTTGCCTTATTTCTCAACCGTTGTGAGTAAGTATCTGACCGACGGATT 
                   
               
               
                   
                 GAATAGGAAAAGTTGTTCTGTGGCTGCTGGGTCTGGGCATTGCTATCTT 
                   
               
               
                   
                 CTCTGCAGCCTAGTATCAGAGCCCGAGCCTGACGACTATGTATCACCAG 
                   
               
               
                   
                 ACCCCACACCGATGAGGTTAGGGGTTCTGACATGGGATGGGTCCTATAC 
                   
               
               
                   
                 TGAACAGGTGGTGCCTGAAAGGATATTCAAAAACATATGGAGTGCAAA 
                   
               
               
                   
                 TTACCCTGGGGTGGGATCAGGTGCTATTGTGGGAAATAAGGTGTTGTTC 
                   
               
               
                   
                 CCATTTTACGGAGGAGTGAGGAATGGGTCGACACCTGAGGTTATGAATA 
                   
               
               
                   
                 GGGGAAGGTATTACTACATTCAAGATCCTAATGATTATTGTCCTGATCC 
                   
               
               
                   
                 ACTGCAAGACCAAATCTTAAGGGCAGAACAATCATATTATCCTACACGG 
                   
               
               
                   
                 TTTGGTAGGAGGATGGTGATGCAGGGTGTCTTAGCGTGCCCAGTGTCCA 
                   
               
               
                   
                 ACAACTCAACAATTGCCAGCCAATGCCAGTCCTACTATTTCAACAACTC 
                   
               
               
                   
                 ATTAGGGTTCATTGGGGCGGAATCTAGGATTTATTACCTAAATGGGAAC 
                   
               
               
                   
                 CTCTACCTTTACCAAAGAAGCTCGAGCTGGTGGCCCCACCCCCAGATTT 
                   
               
               
                   
                 ATCTGCTTGACCCCAGAATTGCAAGCCCGGGCACTCAGAACATCGACTC 
                   
               
               
                   
                 AGGCATTAATCTCAAGATGTTGAATGTTACCGTTATTACACGACCGTCA 
                   
               
               
                   
                 TCTGGTTTTTGTAATAGTCAGTCAAGATGCCCTAATGACTGCTTATTCGG 
                   
               
               
                   
                 GGTCTATTCAGACGTCTGGCCTCTTAGCCTAACCTCAGATAGTATATTCG 
                   
               
               
                   
                 CATTCACGATGTATTTACAAGGGAAGACAACACGTATTGACCCGGCGTG 
                   
               
               
                   
                 GGCACTGTTCTCCAATCACGCAATTGGGCATGAAGCTCGTCTATTCAAC 
                   
               
               
                   
                 AAGGAGGTCAGTGCTGCTTACTCCACTACCACTTGCTTTTCGGACACCA 
                   
               
               
                   
                 TCCAAAACCAGGTGTATTGCCTGAGTATACTTGAAGTTAGAAGTGAGCT 
                   
               
               
                   
                 TTTGGGGCCATTCAAGATAGTACCATTCCTCTACCGTGTCCTATAGGTGC 
                   
               
               
                   
                 CTGCTCGATCGAGAACTCCAAATAATCGTGGAATTAGTACTTAATCTTC 
                   
               
               
                   
                 CCTATGGATATCTGCCTTAATTACTGTCCTAGGTCTCTGGATTAGCGCCC 
                   
               
               
                   
                 TTTAAACCAGTTTTTTGATTTTTAATTAAAAATAGAAGATTAGACCTGGA 
                   
               
               
                   
                 CTCGGGGAGGGAGAAGAACCTATTAGGGTGGGGAAGGATTACTTTACT 
                   
               
               
                   
                 CCATGACTCACAATCGCACACACCTGACCTCATTTCCACTGAGAAGGAA 
                   
               
               
                   
                 CCCTCCTCAAATTTGATTTGCAATGTCCAATCAAGCAGCTGAGATTATA 
                   
               
               
                   
                 CTCCCTACCTTTCACCTAGAGTCACCCTTAATCGAGAACAAATGCTTCTA 
                   
               
               
                   
                 CTATATGCAATTACTTGGTCTTATGTTGCCGCATGATCATTGGAGATGGA 
                   
               
               
                   
                 GGGCATTTGTCAACTTTACAGTGGATCAAGCACACCTTAGAAACCGTAA 
                   
               
               
                   
                 TCCTCGCTTGATGGCCCACATCGACCACACTAAGGATAAACTAAGGGCT 
                   
               
               
                   
                 CATGGTGTCTTAGGTTTCCATCAGACCCAAACAGGTGAGAGCCGTTTCC 
                   
               
               
                   
                 GTGTCTTGCTTCACCCGGAAACCTTACCATGGCTATCAGCAATGGGAGG 
                   
               
               
                   
                 ATGCATAAACCAAGTCCCCAAAGCATGGCGGAACACTCTGAAGTCCATC 
                   
               
               
                   
                 GAGCACAGTGTGAAGCAGGAGGCAACACAACTACAATCGCTTATGAAA 
                   
               
               
                   
                 AAAACCTCATTGAAATTAACAGGAGTACCCTACTTATTTTCCAACTGTA 
                   
               
               
                   
                 ATCCCGGGAAAACCACAACAGGCACTATGCCTGTATTAAGCGAGATGG 
                   
               
               
                   
                 CATCAGAGCTCCTATCAAATCCCATCTCCCAATTCCAATCAACATGGGG 
                   
               
               
                   
                 GTGTGCTGCTTCAGGGTGGCACCATATTGTTAGCATCATGAGGCTTCAA 
                   
               
               
                   
                 CAGTATCAAAGAAGGACAGGTAAAGAGGAGAAGGCGATCACTGAGGTT 
                   
               
               
                   
                 CATTTTGGTTCAGACACCTGTCTCATTAATGCAGACTACACCGTTATCTT 
                   
               
               
                   
                 TTCCTTACAGAGCCGTGTAATAACAGTTTTACCTTTTGACGTTGTCCTCA 
                   
               
               
                   
                 TGATGCAAGACCTGCTCGAATCTCGACGAAATGTCCTGTTCTGTGCCCG 
                   
               
               
                   
                 CTTTATGTACCCCAGAAGCCAATTGCATGAGAGGATAAGCATGATACTA 
                   
               
               
                   
                 GCTCTCGGAGATCAACTTGGGAAAAAGGCACCCCAAGTTCTATATGACT 
                   
               
               
                   
                 TTGTTGCAACCCTTGAATCATTTGCATACGCAGCTGTCCAACTTCATGAC 
                   
               
               
                   
                 AATAACCCTATCTACGGTGGGACTTTCTTTGAATTCAATATCCAAGAATT 
                   
               
               
                   
                 AGAATCTATCTTGTCTCCTGCGCTTAGCAAGGACCAGGTCAACTTCTAC 
                   
               
               
                   
                 ATTAGTCAGGTTGTCTCAGCATACAGTAACCTCCCCCCATCTGAATCGG 
                   
               
               
                   
                 CAGAATTGCTATGCCTGTTACGCCTATGGGGTCACCCTTTACTAAATAG 
                   
               
               
                   
                 CCTCGATGCAGCAAAGAAAGTCAGAGAATCAATGTGTGCCGGGAAGGT 
                   
               
               
                   
                 TCTTGACTACAATGCCATTCGATTAGTCTTGTCTTTTTACCATACATTATT 
                   
               
               
                   
                 GATCAATGGATATCGGAAGAAACACAAGGGACGCTGGCCAAATGTGAA 
                   
               
               
                   
                 TCAACATTCACTACTCAACCCAATAGTGAGGCAGCTTTACTTTGATCAA 
                   
               
               
                   
                 GAAGAGATCCCACATTCTGTCGCCCTCGAACATTACTTAGACATCTCAA 
                   
               
               
                   
                 TGATAGAATTTGAGAAAACTTTTGAGGTTGAACTATCTGACAGCCTAAG 
                   
               
               
                   
                 CATCTTTTTGAAAGACAAGTCGATTGCCTTGGACAAACAAGAGTGGTAC 
                   
               
               
                   
                 AGCGGTTTTGTTTCAGAAGTGACCCCAAAGCACTTGCGGATGTCTCGTC 
                   
               
               
                   
                 ATGACCGCAAGTCCACCAACAGGCTCCTGCTGGCCTTTATCAACTCCCC 
                   
               
               
                   
                 TGAATTCGATGTTAAAGAAGAGCTAAAATACTTGACTACAGGTGAGTAT 
                   
               
               
                   
                 GCTACTGATCCAAATTTCAACGTTTCTTACTCACTTAAAGAGAAGGAAG 
                   
               
               
                   
                 TAAAGAAAGAAGGACGAATCTTTGCAAAAATGTCACAAAAGATGAGAG 
                   
               
               
                   
                 CGTGCCAGGTTATTTGTGAAGAGTTGCTAGCACATCATGTAGCCCCTTT 
                   
               
               
                   
                 GTTTAAAGAGAATGGTGTCACACAGTCGGAACTATCTCTGACAAAAAAT 
                   
               
               
                   
                 CTGCTAGCTATCAGTCAGTTGAGTTATAACTCAATGGCTGCTAAGGTGC 
                   
               
               
                   
                 GGTTGCTGAGACCAGGGGACAAATTCACTGCCGCACACTATATGACCAC 
                   
               
               
                   
                 AGACCTGAAAAAGTACTGCCTTAATTGGCGTCACCAGTCAGTCAAACTG 
                   
               
               
                   
                 TTTGCCAGAAGCCTAGATCGACTGTTCGGGCTAGATCATGCTTTTTCTTG 
                   
               
               
                   
                 GATACATGTCCGCCTCACCAACAGCACCATGTATGTGGCTGATCCATTC 
                   
               
               
                   
                 AATCCACCAGACTCAGATGCATGCCCAAACTTAGACGACAACAAAAAC 
                   
               
               
                   
                 ACGGGAATTTTCATCATAAGTGCACGAGGTGGGATAGAAGGCCTCCAA 
                   
               
               
                   
                 CAAAAACTGTGGACCGGCATATCAATCGCAATCGCGCAAGCAGCTGCA 
                   
               
               
                   
                 GCCCTCGAAGGCTTGAGAATTGCTGCTACTTTGCAGGGGGACAACCAGG 
                   
               
               
                   
                 TTCTAGCGATCACGAAGGAATTTGTAACCCCAGTCCCGGAAGGTGTCCT 
                   
               
               
                   
                 CCATGAGCAATTATCTGAGGCGATGTCCCGATATAAAAAGACTTTCACA 
                   
               
               
                   
                 TACCTTAATTACTTAATGGGGCATCAACTGAAAGATAAAGAGACAATCC 
                   
               
               
                   
                 AATCCAGTGATTTCTTTGTTTACTCTAAAAGGATATTCTTTAATGGGTCC 
                   
               
               
                   
                 ATTCTGAGTCAATGTCTCAAAAACTTCAGTAAGCTCACCACTAATGCCA 
                   
               
               
                   
                 CCACCCTTGCCGAGAACACTGTAGCCGGCTGCAGTGACATCTCATCATG 
                   
               
               
                   
                 CATCGCTCGTTGTGTAGAAAACGGGTTGCCAAAGGATGCTGCATACATC 
                   
               
               
                   
                 CAGAACATAGTCATGACTCGACTTCAACTGTTGCTAGATCACTACTATT 
                   
               
               
                   
                 CCATGCATGGTGGCATAAACTCAGAATTAGAACAGCCGACCCTAAGTAT 
                   
               
               
                   
                 TTCTGTTCGGAATGCAACCTATTTACCATCTCAGTTGGGCGGTTACAATC 
                   
               
               
                   
                 ATCTAAATATGACCCGACTATTTTGCCGCAACATCGGTGACCCGCTCAC 
                   
               
               
                   
                 TAGTTCCTGGGCAGAAGCAAAGAGACTAATGGAAGTTGGCCTGCTCAAT 
                   
               
               
                   
                 CGTAAATTCCTGGAGGGAATATTGTGGCGACCTCCGGGAAGTGGGACAT 
                   
               
               
                   
                 TCTCAACACTTATGCTTGACCCGTTTGCGCTGAACATTGATTACCTCAGA 
                   
               
               
                   
                 CCACCAGAGACAATAATCCGAAAGCATACCCAGAAGGTCTTGCTGCAA 
                   
               
               
                   
                 GATTGCCCTAATCCCCTATTAGCCGGTGTGGTTGATCCGAACTACAACC 
                   
               
               
                   
                 AGGAACTGGAACTATTAGCGCAGTTCTTGCTCGACCGAGAGACCGTTAT 
                   
               
               
                   
                 TCCCAGGGCAGCTCATGCTATCTTTGAGCTGTCTGTCTTGGGGAGGAAA 
                   
               
               
                   
                 AAACATATACAAGGGTTGGTGGACACTACAAAAACGATTATCCAGTGTT 
                   
               
               
                   
                 CGCTGGAAAGACAACCATTGTCCTGGAGGAAAGTTGAGAACATTATCA 
                   
               
               
                   
                 CCTATAATGCGCAGTATTTCCTTGGAGCCACTCAGCAGATTGATACAGA 
                   
               
               
                   
                 TTCCCCTGAAAAGCAGTGGGTGATGCCAAGCAACTTCAAGAAGCTCGTG 
                   
               
               
                   
                 TCTCTTGACGATTGTTCAGTCACATTGTCTACTGTTTCCCGGCGTATATC 
                   
               
               
                   
                 TTGGGCCAACCTACTTAATTGGAGGGCAATAGATGGCTTGGAAACCCCA 
                   
               
               
                   
                 GATGTGATAGAAAGTATTGATGGGCGCCTTGTGCAATCATCCAATCAGT 
                   
               
               
                   
                 GTGGCCTATGTAATCAAGGATTAAGTTCCTACTCCTGGTTCTTCCTCCCC 
                   
               
               
                   
                 TCCGGATGTGTGTTTGATCGTCCACAAGACTCCAGGGTAGTACCGAAAA 
                   
               
               
                   
                 TGCCGTATGTGGGATCCAAGACAGATGAGAGGCAGACTGCGTCGGTAC 
                   
               
               
                   
                 AAGCTATACAGGGATCCACATGTCACCTTAGAGCAGCATTGAGACTTGT 
                   
               
               
                   
                 ATCACTCTACCTTTGGGCTTATGGGGATTCTGATATATCATGGCTGGAA 
                   
               
               
                   
                 GCCGCGACACTAGCCCAAACACGGTGCAATATTTCCCTTGATGATCTGC 
                   
               
               
                   
                 GAATCCTGAGCCCTCTACCTTCCTCGGCAAATTTACACCACAGATTAAA 
                   
               
               
                   
                 TGACGGGGTAACACAAGTGAAATTCATGCCTGCTACATCAAGCCGAGTA 
                   
               
               
                   
                 TCAAAGTTTGTCCAGATTTGCAATGACAACCAGAATCTTATCCGTGATG 
                   
               
               
                   
                 ATGGGAGTGTGGATTCCAATATGATTTATCAGCAAGTCATGATATTAGG 
                   
               
               
                   
                 ACTTGGGGAATTTGAGTGCTTGTTGGCCGACCCAATCGATACTAACCCA 
                   
               
               
                   
                 GAGCAATTGATTCTTCATCTACACTCTGACAATTCTTGCTGCCTCCGGGA 
                   
               
               
                   
                 GATGCCAACAACCGGCTTTGTGCCTGCTTTGGGATTAACCCCATGCTTA 
                   
               
               
                   
                 ACTGTACCAAAGCAAAATCCATATATTTATGACGAGAGTCCAATACCTG 
                   
               
               
                   
                 GTGACCTGGATCAACGGCTCATCCAAACAAAGTTTTTCATGGGTTCTGA 
                   
               
               
                   
                 TAATCTAGACAACCTTGATATCTATCAGCAACGAGCGTTACTAAGTCGG 
                   
               
               
                   
                 TGTGTGGCTTATGATGTTATCCAATCAGTATTTGCTTGTGATGCACCAGT 
                   
               
               
                   
                 TTCTCAGAAGAATGATGCAATCCTCCATACTGACTATCATGAGAATTGG 
                   
               
               
                   
                 ATCTCAGAGTTCCGATGGGGTGACCCTCGGATAATTCAAGTGACAGCAG 
                   
               
               
                   
                 GTTATGAATTGATCTTGTTTCTTGCTTACCAGCTTTATTACCTTAGAGTG 
                   
               
               
                   
                 AGGGGTGACCGTGCAATCCTGTGCTATATTGATAGGATACTGAATAGGA 
                   
               
               
                   
                 TGGTGTCATCAAATCTAGGCAGCCTTATCCAGACACTCTCCCATCCGGA 
                   
               
               
                   
                 GATTAGGAGGAGGTTTTCATTAAGTGATCAAGGATTCCTTGTTGAAAGG 
                   
               
               
                   
                 GAACTAGAGCCAGGCAAACCTTTGGTAAAACAAGCAGTCATGTTCCTAA 
                   
               
               
                   
                 GGGACTCAGTCCGATGTGCTTTAGCAACTATCAAGGCAGGAGTCGAGCC 
                   
               
               
                   
                 GGAGATCTCCCGAGGTGGCTGTACCCAAGATGAGTTGAGTTTCACCCTC 
                   
               
               
                   
                 AAGCACTTGCTATGTCGACGTCTCTGTATAATTGCTCTCATGCATTCAGA 
                   
               
               
                   
                 AGCAAAGAACTTGGTCAAGGTCAGAAATCTCCCAGTAGAGGAAAAATC 
                   
               
               
                   
                 TGCTTTACTATACCAGATGTTGGTCACCGAAGCTAATGCCCGGAAATCA 
                   
               
               
                   
                 GGATCTGCTAGCATCATCATAGGCTTAATTTCGGCACCTCAGTGGGATA 
                   
               
               
                   
                 TCCATACCCCAGCACTGTACTTTGTATCAAAGAAGATGCTAGGAATGCT 
                   
               
               
                   
                 CAAAAGGTCAACTACACCATTGGATGTAAATGATCTGTCTGAGAGCCAG 
                   
               
               
                   
                 GACCTTATGCCAACAGAGTTGAGTGATGGTCCTGGTCACATGGCAGAGG 
                   
               
               
                   
                 GATTTCCCTGTCTATTTAGTAGTTTTAACGCTACATATGAAGACACAATT 
                   
               
               
                   
                 GTTTATAATCCGATGACTGAAAAGCCTGCAGTACATTTGGACAATGGAT 
                   
               
               
                   
                 CCACCCCATCCAGGGCGCTAGGTCGCCACTACATCTTGCGGCCCCTCGG 
                   
               
               
                   
                 GCTTTACTCGTCTGCATGGTACCGGTCTGCAGCACTCTTAGCATCAGGTG 
                   
               
               
                   
                 CTCTCAATGGGTTACCGGAGGGATCAAGCCTATACTTGGGAGAAGGGTA 
                   
               
               
                   
                 TGGGACCACCATGACTCTGCTCGAACCCGTCGTCAAGTCCTCAACTGTT 
                   
               
               
                   
                 TATTACCACACATTGTTTGACCCGACCCGGAATCCCTCACAGCGGAATT 
                   
               
               
                   
                 ACAAACCAGAGCCGCGAGTCTTCACTGATTCCATCTGGTACAAGGATGA 
                   
               
               
                   
                 CTTCACACGACCGCCTGGTGGCATTGTAAATCTATGGGGTGAAGATGTG 
                   
               
               
                   
                 CGTCAGAGTGACGTCACACAGAAAGACACAGTTAATTTCATATTATCCC 
                   
               
               
                   
                 GGATCCCACCCAAATCACTCAAACTGATCCATGTTGACATTGAATTCTC 
                   
               
               
                   
                 ACCAGACTCCAATGTACGGACACTACTATCTGGTTACTCCCATTGCGCA 
                   
               
               
                   
                 TTATTGGCCTACTGGCTATTGCAACCTGGAGGGCGATTTGCGGTTAGGG 
                   
               
               
                   
                 TCTTCCTGAGTGACCATCTCTTAGTAAACTTGGTCACTGCTATTCTGTCT 
                   
               
               
                   
                 GCTTTCGACTCTAATCTACTGTGTATTGCATCTGGATTGACACACAAAG 
                   
               
               
                   
                 ATGATGGGGCAGGTTACATTTGTGCTAAGAAGCTTGCCAATGTTGAGGC 
                   
               
               
                   
                 ATCAAGGATTGAGCACTACTTAAGGATGGTCCATGGTTGCGTTGATTCA 
                   
               
               
                   
                 TTAAAGATCCCCCACCAACTAGGGATCATTAAGTGGGCTGAAGGTGAG 
                   
               
               
                   
                 GTGTCTCGGCTCACAAAAAAGGCAGATGAAGAAATAAATTGGCGATTA 
                   
               
               
                   
                 GGTGACCCGGTTACTAGATCATTTGATCCAGTTTCCGAGTTAATAATCG 
                   
               
               
                   
                 CACGGACAGGGGGGTCTGTATTAATGGAATATGGGACTTTCATTAATCT 
                   
               
               
                   
                 CAGGTGTTCAAACCTGGCAGATACATATAAACTTTTGGCTTCAATCGTG 
                   
               
               
                   
                 GAGACCACCTTGATGGAGATAAGGGTTGAACAAGATCAATTGGAAGAC 
                   
               
               
                   
                 AACTCAAGAAGACAAATTCAGGTGGTCCCCGCCTTTAATACGAGATCCG 
                   
               
               
                   
                 GGGGGAGGATCCGTACATTGATTGAGTGTGCCCAGCTGCAGGTTATAGA 
                   
               
               
                   
                 TGTCATATGTGTAAACATAGATCACCTCTTCCCCAAACATCGACATGTTC 
                   
               
               
                   
                 TTGTTACACAACTCACTTACCAGTCAGTGTGCCTTGGAGACTTGATCGA 
                   
               
               
                   
                 GGGGCCCCAAATTAAGATGTATCTAAGGGCCAGGAAGTGGATCCAACG 
                   
               
               
                   
                 TAGAGGACTCAATGAGACAATTAACCATATCATCACTGGACAGATATCA 
                   
               
               
                   
                 CGAAATAAGGCAAGGGATTTCTTCAAGAGGCGCCTGAAGTTGGTTGGCT 
                   
               
               
                   
                 TCTCGCTTTGCGGCGGTTGGAGTTACCTCTCACTTTAGTTACTTAGGTTG 
                   
               
               
                   
                 TTGATCATTGTGAAAAATCGGAGTCGGAATCGCAAATAAAAACATACA 
                   
               
               
                   
                 AAATTGCAAATTTACAATAATCGCATTAATATTTAATAAAAAATATGTC 
                   
               
               
                   
                 TTTTATTTCGT 
                   
               
               
                 Newcastle di- 
                 ACCAAACAGAGAATCCGTGAGTTACGATAAAAGGCGAAAGAGCAATTG 
                 83 
               
               
                 sease virus 
                 AAGTCACACGGGTAGAAGGTGTGAATCTCGAGTGCGAGCCCGAAGCAC 
                   
               
               
                 strain 
                 AAACTCGAGAAAGCCTTCTGCCAACATGTCCTCCGTATTTGATGAGTAC 
                   
               
               
                 LaSota, 
                 GAACAGCTCCTCGCGGCTCAGACTCGCCCCAACGGAGCTCATGGAGGG 
                   
               
               
                 complete 
                 GGAGAAAAAGGGAGTACCTTAAAAGTAGACGTCCCGGTATTCACTCTTA 
                   
               
               
                 genome with 
                 ACAGTGATGACCCAGAAGATAGATGGAGCTTTGTGGTATTCTGCCTCCG 
                   
               
               
                 modification 
                 GATTGCTGTTAGCGAAGATGCCAACAAACCACTCAGGCAAGGTGCTCTC 
                   
               
               
                 in 5408- 
                 ATATCTCTTTTATGCTCCCACTCACAGGTAATGAGGAACCATGTTGCCCT 
                   
               
               
                 5409-5410 
                 TGCAGGGAAACAGAATGAAGCCACATTGGCCGTGCTTGAGATTGATGG 
                   
               
               
                 nucleotides 
                 CTTTGCCAACGGCACGCCCCAGTTCAATAATAGGAGTGGAGTGTCTGAA 
                   
               
               
                 resulting in 
                 GAGAGAGCACAGAGATTTGCGATGATAGCAGGATCTCTCCCTCGGGCAT 
                   
               
               
                 L289A 
                 GCAGCAACGGAACCCCGTTCGTCACAGCCGGGGCCGAAGATGATGCAC 
                   
               
               
                 substitution 
                 CAGAAGACATCACCGATACCCTGGAGAGGATCCTCTCTATCCAGGCTCA 
                   
               
               
                   
                 AGTATGGGTCACAGTAGCAAAAGCCATTACTGCGTATGAGACTGCAGAT 
                   
               
               
                   
                 GAGTCGGAAACAAGGCGAATCAATAAGTATATGCAGCAAGGCAGGGTC 
                   
               
               
                   
                 CAAAAGAAATACATCCTCTACCCCGTATGCAGGAGCACAATCCAACTCA 
                   
               
               
                   
                 CGATCAGACAGTCTCTTGCAGTCCGCATCTTTTTGGTTAGCGAGCTCAA 
                   
               
               
                   
                 GAGAGGCCGCAACACGGCAGGTGGTACCTCTACTTATTATAACCTGGTA 
                   
               
               
                   
                 GGGGACGTAGACTCATACATCAGGAATACCGGGCTTACTGCATTCTTCT 
                   
               
               
                   
                 TGACACTCAAGTACGGAATCAACACCAAGACATCAGCCCTTGCACTTAG 
                   
               
               
                   
                 TAGCCTCTCAGGCGACATCCAGAAGATGAAGCAGCTCATGCGTTTGTAT 
                   
               
               
                   
                 CGGATGAAAGGAGATAATGCGCCGTACATGACATTACTTGGTGATAGTG 
                   
               
               
                   
                 ACCAGATGAGCTTTGCGCCTGCCGAGTATGCACAACTTTACTCCTTTGCC 
                   
               
               
                   
                 ATGGGTATGGCATCAGTCCTAGATAAAGGTACTGGGAAATACCAATTTG 
                   
               
               
                   
                 CCAGGGACTTTATGAGCACATCATTCTGGAGACTTGGAGTAGAGTACGC 
                   
               
               
                   
                 TCAGGCTCAGGGAAGTAGCATTAACGAGGATATGGCTGCCGAGCTAAA 
                   
               
               
                   
                 GCTAACCCCAGCAGCAAGGAGGGGCCTGGCAGCTGCTGCCCAACGGGT 
                   
               
               
                   
                 CTCCGAGGAGACCAGCAGCATAGACATGCCTACTCAACAAGTCGGAGT 
                   
               
               
                   
                 CCTCACTGGGCTTAGCGAGGGGGGGTCCCAAGCTCTACAAGGCGGATC 
                   
               
               
                   
                 GAATAGATCGCAAGGGCAACCAGAAGCCGGGGATGGGGAGACCCAATT 
                   
               
               
                   
                 CCTGGATCGGATGAGAGCGGTAGCAAATAGCATGAGGGAGGCGCCAAA 
                   
               
               
                   
                 CTCTGCACAGGGCACTCCCCAATCGGGGCCTCCCCCAACTCCTGGGCCA 
                   
               
               
                   
                 TCCCAAGATAACGACACCGACTGGGGGTATTGATGGACAAAACCCAGC 
                   
               
               
                   
                 CTGCTTCCACAAAAACATCCCAATGCCCTCACCCGTAGTCGACCCCTCG 
                   
               
               
                   
                 ATTTGCGGCTCTATATGACCACACCCTCAAACAAACATCCCCCTCTTTCC 
                   
               
               
                   
                 TCCCTCCCCCTGCTGTACAACTCCGCACGCCCTAGATACCACAGGCACA 
                   
               
               
                   
                 ATGCGGCTCACTAACAATCAAAACAGAGCCGAGGGAATTAGAAAAAAG 
                   
               
               
                   
                 TACGGGTAGAAGAGGGATATTCAGAGATCAGGGCAAGTCTCCCGAGTC 
                   
               
               
                   
                 TCTGCTCTCTCCTCTACCTGATAGACCAGGACAAACATGGCCACCTTTAC 
                   
               
               
                   
                 AGATGCAGAGATCGACGAGCTATTTGAGACAAGTGGAACTGTCATTGA 
                   
               
               
                   
                 CAACATAATTACAGCCCAGGGTAAACCAGCAGAGACTGTTGGAAGGAG 
                   
               
               
                   
                 TGCAATCCCACAAGGCAAGACCAAGGTGCTGAGCGCAGCATGGGAGAA 
                   
               
               
                   
                 GCATGGGAGCATCCAGCCACCGGCCAGTCAAGACAACCCCGATCGACA 
                   
               
               
                   
                 GGACAGATCTGACAAACAACCATCCACACCCGAGCAAACGACCCCGCA 
                   
               
               
                   
                 TGACAGCCCGCCGGCCACATCCGCCGACCAGCCCCCCACCCAGGCCACA 
                   
               
               
                   
                 GACGAAGCCGTCGACACACAGCTCAGGACCGGAGCAAGCAACTCTCTG 
                   
               
               
                   
                 CTGTTGATGCTTGACAAGCTCAGCAATAAATCGTCCAATGCTAAAAAGG 
                   
               
               
                   
                 GCCCATGGTCGAGCCCCCAAGAGGGGAATCACCAACGTCCGACTCAAC 
                   
               
               
                   
                 AGCAGGGGAGTCAACCCAGTCGCGGAAACAGTCAGGAAAGACCGCAGA 
                   
               
               
                   
                 ACCAAGTCAAGGCCGCCCCTGGAAACCAGGGCACAGACGTGAACACAG 
                   
               
               
                   
                 CATATCATGGACAATGGGAGGAGTCACAACTATCAGCTGGTGCAACCCC 
                   
               
               
                   
                 TCATGCTCTCCGATCAAGGCAGAGCCAAGACAATACCCTTGTATCTGCG 
                   
               
               
                   
                 GATCATGTCCAGCCACCTGTAGACTTTGTGCAAGCGATGATGTCTATGA 
                   
               
               
                   
                 TGGAGGCGATATCACAGAGAGTAAGTAAGGTCGACTATCAGCTAGATC 
                   
               
               
                   
                 TTGTCTTGAAACAGACATCCTCCATCCCTATGATGCGGTCCGAAATCCA 
                   
               
               
                   
                 ACAGCTGAAAACATCTGTTGCAGTCATGGAAGCCAACTTGGGAATGATG 
                   
               
               
                   
                 AAGATTCTGGATCCCGGTTGTGCCAACATTTCATCTCTGAGTGATCTACG 
                   
               
               
                   
                 GGCAGTTGCCCGATCTCACCCGGTTTTAGTTTCAGGCCCTGGAGACCCC 
                   
               
               
                   
                 TCTCCCTATGTGACACAAGGAGGCGAAATGGCACTTAATAAACTTTCGC 
                   
               
               
                   
                 AACCAGTGCCACATCCATCTGAATTGATTAAACCCGCCACTGCATGCGG 
                   
               
               
                   
                 GCCTGATATAGGAGTGGAAAAGGACACTGTCCGTGCATTGATCATGTCA 
                   
               
               
                   
                 CGCCCAATGCACCCGAGTTCTTCAGCCAAGCTCCTAAGCAAGTTAGATG 
                   
               
               
                   
                 CAGCCGGGTCGATCGAGGAAATCAGGAAAATCAAGCGCCTTGCTCTAA 
                   
               
               
                   
                 ATGGCTAATTACTACTGCCACACGTAGCGGGTCCCTGTCCACTCGGCAT 
                   
               
               
                   
                 CACACGGAATCTGCACCGAGTTCCCCCCCGCAGACCCAAGGTCCAACTC 
                   
               
               
                   
                 TCCAAGCGGCAATCCTCTCTCGCTTCCTCAGCCCCACTGAATGATCGCGT 
                   
               
               
                   
                 AACCGTAATTAATCTAGCTACATTTAAGATTAAGAAAAAATACGGGTAG 
                   
               
               
                   
                 AATTGGAGTGCCCCAATTGTGCCAAGATGGACTCATCTAGGACAATTGG 
                   
               
               
                   
                 GCTGTACTTTGATTCTGCCCATTCTTCTAGCAACCTGTTAGCATTTCCGA 
                   
               
               
                   
                 TCGTCCTACAAGACACAGGAGATGGGAAGAAGCAAATCGCCCCGCAAT 
                   
               
               
                   
                 ATAGGATCCAGCGCCTTGACTTGTGGACTGATAGTAAGGAGGACTCAGT 
                   
               
               
                   
                 ATTCATCACCACCTATGGATTCATCTTTCAAGTTGGGAATGAAGAAGCC 
                   
               
               
                   
                 ACTGTCGGCATGATCGATGATAAACCCAAGCGCGAGTTACTTTCCGCTG 
                   
               
               
                   
                 CGATGCTCTGCCTAGGAAGCGTCCCAAATACCGGAGACCTTATTGAGCT 
                   
               
               
                   
                 GGCAAGGGCCTGTCTCACTATGATAGTCACATGCAAGAAGAGTGCAACT 
                   
               
               
                   
                 AATACTGAGAGAATGGTTTTCTCAGTAGTGCAGGCACCCCAAGTGCTGC 
                   
               
               
                   
                 AAAGCTGTAGGGTTGTGGCAAACAAATACTCATCAGTGAATGCAGTCA 
                   
               
               
                   
                 AGCACGTGAAAGCGCCAGAGAAGATTCCCGGGAGTGGAACCCTAGAAT 
                   
               
               
                   
                 ACAAGGTGAACTTTGTCTCCTTGACTGTGGTACCGAAGAAGGATGTCTA 
                   
               
               
                   
                 CAAGATCCCTGCTGCAGTATTGAAGGTTTCTGGCTCGAGTCTGTACAAT 
                   
               
               
                   
                 CTTGCGCTCAATGTCACTATTAATGTGGAGGTAGACCCGAGGAGTCCTT 
                   
               
               
                   
                 TGGTTAAATCTCTGTCTAAGTCTGACAGCGGATACTATGCTAACCTCTTC 
                   
               
               
                   
                 TTGCATATTGGACTTATGACCACCGTAGATAGGAAGGGGAAGAAAGTG 
                   
               
               
                   
                 ACATTTGACAAGCTGGAAAAGAAAATAAGGAGCCTTGATCTATCTGTCG 
                   
               
               
                   
                 GGCTCAGTGATGTGCTCGGGCCTTCCGTGTTGGTAAAAGCAAGAGGTGC 
                   
               
               
                   
                 ACGGACTAAGCTTTTGGCACCTTTCTTCTCTAGCAGTGGGACAGCCTGCT 
                   
               
               
                   
                 ATCCCATAGCAAATGCTTCTCCTCAGGTGGCCAAGATACTCTGGAGTCA 
                   
               
               
                   
                 AACCGCGTGCCTGCGGAGCGTTAAAATCATTATCCAAGCAGGTACCCAA 
                   
               
               
                   
                 CGCGCTGTCGCAGTGACCGCCGACCACGAGGTTACCTCTACTAAGCTGG 
                   
               
               
                   
                 AGAAGGGGCACACCCTTGCCAAATACAATCCTTTTAAGAAATAAGCTGC 
                   
               
               
                   
                 GTCTCTGAGATTGCGCTCCGCCCACTCACCCAGATCATCATGACACAAA 
                   
               
               
                   
                 AAACTAATCTGTCTTGATTATTTACAGTTAGTTTACCTGTCTATCAAGTT 
                   
               
               
                   
                 AGAAAAAACACGGGTAGAAGATTCTGGATCCCGGTTGGCGCCCTCCAG 
                   
               
               
                   
                 GTGCAAGATGGGCTCCAGACCTTCTACCAAGAACCCAGCACCTATGATG 
                   
               
               
                   
                 CTGACTATCCGGGTTGCGCTGGTACTGAGTTGCATCTGTCCGGCAAACT 
                   
               
               
                   
                 CCATTGATGGCAGGCCTCTTGCAGCTGCAGGAATTGTGGTTACAGGAGA 
                   
               
               
                   
                 CAAAGCCGTCAACATATACACCTCATCCCAGACAGGATCAATCATAGTT 
                   
               
               
                   
                 AAGCTCCTCCCGAATCTGCCCAAGGATAAGGAGGCATGTGCGAAAGCC 
                   
               
               
                   
                 CCCTTGGATGCATACAACAGGACATTGACCACTTTGCTCACCCCCCTTG 
                   
               
               
                   
                 GTGACTCTATCCGTAGGATACAAGAGTCTGTGACTACATCTGGAGGGGG 
                   
               
               
                   
                 GAGACAGGGGCGCCTTATAGGTGCCATTATTGGCGGTGTGGCTCTTGGG 
                   
               
               
                   
                 GTTGCAACTGCCGCACAAATAACAGCGGCCGCAGCTCTGATACAAGCC 
                   
               
               
                   
                 AAACAAAATGCTGCCAACATCCTCCGACTTAAAGAGAGCATTGCCGCA 
                   
               
               
                   
                 ACCAATGAGGCTGTGCATGAGGTCACTGACGGATTATCGCAACTAGCAG 
                   
               
               
                   
                 TGGCAGTTGGGAAGATGCAGCAGTTTGTTAATGACCAATTTAATAAAAC 
                   
               
               
                   
                 AGCTCAGGAATTAGACTGCATCAAAATTGCACAGCAAGTTGGTGTAGA 
                   
               
               
                   
                 GCTCAACCTGTACCTAACCGAATTGACTACAGTATTCGGACCACAAATC 
                   
               
               
                   
                 ACTTCACCCGCTTTAAACAAGCTGACTATTCAGGCACTTTACAATCTAG 
                   
               
               
                   
                 CTGGTGGAAATATGGATTACTTATTGACTAAGTTAGGTGTAGGGAACAA 
                   
               
               
                   
                 TCAACTCAGCTCATTAATCGGTAGCGGCTTAATCACCGGTAACCCTATT 
                   
               
               
                   
                 CTATACGACTCACAGACTCAACTCTTGGGTATACAGGTAACTGCCCCTT 
                   
               
               
                   
                 CAGTCGGGAACCTAAATAATATGCGTGCCACCTACTTGGAAACCTTATC 
                   
               
               
                   
                 CGTAAGCACAACCAGGGGATTTGCCTCGGCACTTGTCCCAAAAGTGGTG 
                   
               
               
                   
                 ACACAGGTCGGTTCTGTGATAGAAGAACTTGACACCTCATACTGTATAG 
                   
               
               
                   
                 AAACTGACTTAGATTTATATTGTACAAGAATAGTAACGTTCCCTATGTC 
                   
               
               
                   
                 CCCTGGTATTTATTCCTGCTTGAGCGGCAATACGTCGGCCTGTATGTACT 
                   
               
               
                   
                 CAAAGACCGAAGGCGCACTTACTACACCATACATGACTATCAAAGGTTC 
                   
               
               
                   
                 AGTCATCGCCAACTGCAAGATGACAACATGTAGATGTGTAAACCCCCCG 
                   
               
               
                   
                 GGTATCATATCGCAAAACTATGGAGAAGCCGTGTCTCTAATAGATAAAC 
                   
               
               
                   
                 AATCATGCAATGTTTTATCCTTAGGCGGGATAACTTTAAGGCTCAGTGG 
                   
               
               
                   
                 GGAATTCGATGTAACTTATCAGAAGAATATCTCAATACAAGATTCTCAA 
                   
               
               
                   
                 GTAATAATAACAGGCAATCTTGATATCTCAACTGAGCTTGGGAATGTCA 
                   
               
               
                   
                 ACAACTCGATCAGTAATGCTTTGAATAAGTTAGAGGAAAGCAACAGAA 
                   
               
               
                   
                 AACTAGACAAAGTCAATGTCAAACTGACTAGCACATCTGCCCTCATTAC 
                   
               
               
                   
                 CTATATCGTTTTGACTATCATATCTCTTGTTTTTGGTATACTTAGCCTGAT 
                   
               
               
                   
                 TCTAGCATGCTACCTAATGTACAAGCAAAAGGCGCAACAAAAGACCTT 
                   
               
               
                   
                 ATTATGGCTTGGGAATAATACTCTAGATCAGATGAGAGCCACTACAAAA 
                   
               
               
                   
                 ATGTGAACACAGATGAGGAACGAAGGTTTCCCTAATAGTAATTTGTGTG 
                   
               
               
                   
                 AAAGTTCTGGTAGTCTGTCAGTTCAGAGAGTTAAGAAAAAACTACCGGT 
                   
               
               
                   
                 TGTAGATGACCAAAGGACGATATACGGGTAGAACGGTAAGAGAGGCCG 
                   
               
               
                   
                 CCCCTCAATTGCGAGCCAGGCTTCACAACCTCCGTTCTACCGCTTCACCG 
                   
               
               
                   
                 ACAACAGTCCTCAATCATGGACCGCGCCGTTAGCCAAGTTGCGTTAGAG 
                   
               
               
                   
                 AATGATGAAAGAGAGGCAAAAAATACATGGCGCTTGATATTCCGGATT 
                   
               
               
                   
                 GCAATCTTATTCTTAACAGTAGTGACCTTGGCTATATCTGTAGCCTCCCT 
                   
               
               
                   
                 TTTATATAGCATGGGGGCTAGCACACCTAGCGATCTTGTAGGCATACCG 
                   
               
               
                   
                 ACTAGGATTTCCAGGGCAGAAGAAAAGATTACATCTACACTTGGTTCCA 
                   
               
               
                   
                 ATCAAGATGTAGTAGATAGGATATATAAGCAAGTGGCCCTTGAGTCTCC 
                   
               
               
                   
                 GTTGGCATTGTTAAAAACTGAGACCACAATTATGAACGCAATAACATCT 
                   
               
               
                   
                 CTCTCTTATCAGATTAATGGAGCTGCAAACAACAGTGGGTGGGGGGCAC 
                   
               
               
                   
                 CTATCCATGACCCAGATTATATAGGGGGGATAGGCAAAGAACTCATTGT 
                   
               
               
                   
                 AGATGATGCTAGTGATGTCACATCATTCTATCCCTCTGCATTTCAAGAAC 
                   
               
               
                   
                 ATCTGAATTTTATCCCGGCGCCTACTACAGGATCAGGTTGCACTCGAAT 
                   
               
               
                   
                 ACCCTCATTTGACATGAGTGCTACCCATTACTGCTACACCCATAATGTA 
                   
               
               
                   
                 ATATTGTCTGGATGCAGAGATCACTCACATTCATATCAGTATTTAGCACT 
                   
               
               
                   
                 TGGTGTGCTCCGGACATCTGCAACAGGGAGGGTATTCTTTTCTACTCTGC 
                   
               
               
                   
                 GTTCCATCAACCTGGACGACACCCAAAATCGGAAGTCTTGCAGTGTGAG 
                   
               
               
                   
                 TGCAACTCCCCTGGGTTGTGATATGCTGTGCTCGAAAGTCACGGAGACA 
                   
               
               
                   
                 GAGGAAGAAGATTATAACTCAGCTGTCCCTACGCGGATGGTACATGGG 
                   
               
               
                   
                 AGGTTAGGGTTCGACGGCCAGTACCACGAAAAGGACCTAGATGTCACA 
                   
               
               
                   
                 ACATTATTCGGGGACTGGGTGGCCAACTACCCAGGAGTAGGGGGTGGA 
                   
               
               
                   
                 TCTTTTATTGACAGCCGCGTATGGTTCTCAGTCTACGGAGGGTTAAAAC 
                   
               
               
                   
                 CCAATTCACCCAGTGACACTGTACAGGAAGGGAAATATGTGATATACA 
                   
               
               
                   
                 AGCGATACAATGACACATGCCCAGATGAGCAAGACTACCAGATTCGAA 
                   
               
               
                   
                 TGGCCAAGTCTTCGTATAAGCCTGGACGGTTTGGTGGGAAACGCATACA 
                   
               
               
                   
                 GCAGGCTATCTTATCTATCAAGGTGTCAACATCCTTAGGCGAAGACCCG 
                   
               
               
                   
                 GTACTGACTGTACCGCCCAACACAGTCACACTCATGGGGGCCGAAGGC 
                   
               
               
                   
                 AGAATTCTCACAGTAGGGACATCTCATTTCTTGTATCAACGAGGGTCAT 
                   
               
               
                   
                 CATACTTCTCTCCCGCGTTATTATATCCTATGACAGTCAGCAACAAAAC 
                   
               
               
                   
                 AGCCACTCTTCATAGTCCTTATACATTCAATGCCTTCACTCGGCCAGGTA 
                   
               
               
                   
                 GTATCCCTTGCCAGGCTTCAGCAAGATGCCCCAACCCGTGTGTTACTGG 
                   
               
               
                   
                 AGTCTATACAGATCCATATCCCCTAATCTTCTATAGAAACCACACCTTGC 
                   
               
               
                   
                 GAGGGGTATTCGGGACAATGCTTGATGGTGTACAAGCAAGACTTAACCC 
                   
               
               
                   
                 TGCGTCTGCAGTATTCGATAGCACATCCCGCAGTCGCATTACTCGAGTG 
                   
               
               
                   
                 AGTTCAAGCAGTACCAAAGCAGCATACACAACATCAACTTGTTTTAAAG 
                   
               
               
                   
                 TGGTCAAGACTAATAAGACCTATTGTCTCAGCATTGCTGAAATATCTAA 
                   
               
               
                   
                 TACTCTCTTCGGAGAATTCAGAATCGTCCCGTTACTAGTTGAGATCCTCA 
                   
               
               
                   
                 AAGATGACGGGGTTAGAGAAGCCAGGTCTGGCTAGTTGAGTCAATTAT 
                   
               
               
                   
                 AAAGGAGTTGGAAAGATGGCATTGTATCACCTATCTTCCACGACATCAA 
                   
               
               
                   
                 GAATCAAACCGAATGCCGGCGCGTGCTCGAATTCCATGTTGCCAGTTGA 
                   
               
               
                   
                 CCACAATCAGCCAGTGCTCATGCGATCAGATTAAGCCTTGTCAATAGTC 
                   
               
               
                   
                 TCTTGATTAAGAAAAAATGTAAGTGGCAATGAGATACAAGGCAAAACA 
                   
               
               
                   
                 GCTCATGGTAAATAATACGGGTAGGACATGGCGAGCTCCGGTCCTGAA 
                   
               
               
                   
                 AGGGCAGAGCATCAGATTATCCTACCAGAGTCACACCTGTCTTCACCAT 
                   
               
               
                   
                 TGGTCAAGCACAAACTACTCTATTACTGGAAATTAACTGGGCTACCGCT 
                   
               
               
                   
                 TCCTGATGAATGTGACTTCGACCACCTCATTCTCAGTCGACAATGGAAA 
                   
               
               
                   
                 AAAATACTTGAATCGGCCTCTCCTGATACTGAGAGAATGATAAAACTCG 
                   
               
               
                   
                 GAAGGGCAGTACACCAAACTCTTAACCACAATTCCAGAATAACCGGAG 
                   
               
               
                   
                 TGCTCCACCCCAGGTGTTTAGAAGAACTGGCTAATATTGAGGTCCCAGA 
                   
               
               
                   
                 TTCAACCAACAAATTTCGGAAGATTGAGAAGAAGATCCAAATTCACAA 
                   
               
               
                   
                 CACGAGATATGGAGAACTGTTCACAAGGCTGTGTACGCATATAGAGAA 
                   
               
               
                   
                 GAAACTGCTGGGGTCATCTTGGTCTAACAATGTCCCCCGGTCAGAGGAG 
                   
               
               
                   
                 TTCAGCAGCATTCGTACGGATCCGGCATTCTGGTTTCACTCAAAATGGT 
                   
               
               
                   
                 CCACAGCCAAGTTTGCATGGCTCCATATAAAACAGATCCAGAGGCATCT 
                   
               
               
                   
                 GATGGTGGCAGCTAGGACAAGGTCTGCGGCCAACAAATTGGTGATGCT 
                   
               
               
                   
                 AACCCATAAGGTAGGCCAAGTCTTTGTCACTCCTGAACTTGTCGTTGTG 
                   
               
               
                   
                 ACGCATACGAATGAGAACAAGTTCACATGTCTTACCCAGGAACTTGTAT 
                   
               
               
                   
                 TGATGTATGCAGATATGATGGAGGGCAGAGATATGGTCAACATAATATC 
                   
               
               
                   
                 AACCACGGCGGTGCATCTCAGAAGCTTATCAGAGAAAATTGATGACATT 
                   
               
               
                   
                 TTGCGGTTAATAGACGCTCTGGCAAAAGACTTGGGTAATCAAGTCTACG 
                   
               
               
                   
                 ATGTTGTATCACTAATGGAGGGATTTGCATACGGAGCTGTCCAGCTACT 
                   
               
               
                   
                 CGAGCCGTCAGGTACATTTGCAGGAGATTTCTTCGCATTCAACCTGCAG 
                   
               
               
                   
                 GAGCTTAAAGACATTCTAATTGGCCTCCTCCCCAATGATATAGCAGAAT 
                   
               
               
                   
                 CCGTGACTCATGCAATCGCTACTGTATTCTCTGGTTTAGAACAGAATCA 
                   
               
               
                   
                 AGCAGCTGAGATGTTGTGTCTGTTGCGTCTGTGGGGTCACCCACTGCTT 
                   
               
               
                   
                 GAGTCCCGTATTGCAGCAAAGGCAGTCAGGAGCCAAATGTGCGCACCG 
                   
               
               
                   
                 AAAATGGTAGACTTTGATATGATCCTTCAGGTACTGTCTTTCTTCAAGGG 
                   
               
               
                   
                 AACAATCATCAACGGGTACAGAAAGAAGAATGCAGGTGTGTGGCCGCG 
                   
               
               
                   
                 AGTCAAAGTGGATACAATATATGGGAAGGTCATTGGGCAACTACATGC 
                   
               
               
                   
                 AGATTCAGCAGAGATTTCACACGATATCATGTTGAGAGAGTATAAGAGT 
                   
               
               
                   
                 TTATCTGCACTTGAATTTGAGCCATGTATAGAATATGACCCTGTCACCA 
                   
               
               
                   
                 ACCTGAGCATGTTCCTAAAAGACAAGGCAATCGCACACCCCAACGATA 
                   
               
               
                   
                 ATTGGCTTGCCTCGTTTAGGCGGAACCTTCTCTCCGAAGACCAGAAGAA 
                   
               
               
                   
                 ACATGTAAAAGAAGCAACTTCGACTAATCGCCTCTTGATAGAGTTTTTA 
                   
               
               
                   
                 GAGTCAAATGATTTTGATCCATATAAAGAGATGGAATATCTGACGACCC 
                   
               
               
                   
                 TTGAGTACCTTAGAGATGACAATGTGGCAGTATCATACTCGCTCAAGGA 
                   
               
               
                   
                 GAAGGAAGTGAAAGTTAATGGACGGATCTTCGCTAAGCTGACAAAGAA 
                   
               
               
                   
                 GTTAAGGAACTGTCAGGTGATGGCGGAAGGGATCCTAGCCGATCAGAT 
                   
               
               
                   
                 TGCACCTTTCTTTCAGGGAAATGGAGTCATTCAGGATAGCATATCCTTG 
                   
               
               
                   
                 ACCAAGAGTATGCTAGCGATGAGTCAACTGTCTTTTAACAGCAATAAGA 
                   
               
               
                   
                 AACGTATCACTGACTGTAAAGAAAGAGTATCTTCAAACCGCAATCATGA 
                   
               
               
                   
                 TCCGAAAAGCAAGAACCGTCGGAGAGTTGCAACCTTCATAACAACTGA 
                   
               
               
                   
                 CCTGCAAAAGTACTGTCTTAATTGGAGATATCAGACAATCAAATTGTTC 
                   
               
               
                   
                 GCTCATGCCATCAATCAGTTGATGGGCCTACCTCACTTCTTCGAATGGAT 
                   
               
               
                   
                 TCACCTAAGACTGATGGACACTACGATGTTCGTAGGAGACCCTTTCAAT 
                   
               
               
                   
                 CCTCCAAGTGACCCTACTGACTGTGACCTCTCAAGAGTCCCTAATGATG 
                   
               
               
                   
                 ACATATATATTGTCAGTGCCAGAGGGGGTATCGAAGGATTATGCCAGAA 
                   
               
               
                   
                 GCTATGGACAATGATCTCAATTGCTGCAATCCAACTTGCTGCAGCTAGA 
                   
               
               
                   
                 TCGCATTGTCGTGTTGCCTGTATGGTACAGGGTGATAATCAAGTAATAG 
                   
               
               
                   
                 CAGTAACGAGAGAGGTAAGATCAGACGACTCTCCGGAGATGGTGTTGA 
                   
               
               
                   
                 CACAGTTGCATCAAGCCAGTGATAATTTCTTCAAGGAATTAATTCATGT 
                   
               
               
                   
                 CAATCATTTGATTGGCCATAATTTGAAGGATCGTGAAACCATCAGGTCA 
                   
               
               
                   
                 GACACATTCTTCATATACAGCAAACGAATCTTCAAAGATGGAGCAATCC 
                   
               
               
                   
                 TCAGTCAAGTCCTCAAAAATTCATCTAAATTAGTGCTAGTGTCAGGTGA 
                   
               
               
                   
                 TCTCAGTGAAAACACCGTAATGTCCTGTGCCAACATTGCCTCTACTGTA 
                   
               
               
                   
                 GCACGGCTATGCGAGAACGGGCTTCCCAAAGACTTCTGTTACTATTTAA 
                   
               
               
                   
                 ACTATATAATGAGTTGTGTGCAGACATACTTTGACTCTGAGTTCTCCATC 
                   
               
               
                   
                 ACCAACAATTCGCACCCCGATCTTAATCAGTCGTGGATTGAAGACATCT 
                   
               
               
                   
                 CTTTTGTGCACTCATATGTTCTGACTCCTGCCCAATTAGGGGGACTGAGT 
                   
               
               
                   
                 AACCTTCAATACTCAAGGCTCTACACTAGAAATATCGGTGACCCGGGGA 
                   
               
               
                   
                 CTACTGCTTTTGCAGAGATCAAGCGACTAGAAGCAGTGGGATTACTGAG 
                   
               
               
                   
                 TCCTAACATTATGACTAATATCTTAACTAGGCCGCCTGGGAATGGAGAT 
                   
               
               
                   
                 TGGGCCAGTCTGTGCAACGACCCATACTCTTTCAATTTTGAGACTGTTGC 
                   
               
               
                   
                 AAGCCCAAATATTGTTCTTAAGAAACATACGCAAAGAGTCCTATTTGAA 
                   
               
               
                   
                 ACTTGTTCAAATCCCTTATTGTCTGGAGTGCACACAGAGGATAATGAGG 
                   
               
               
                   
                 CAGAAGAGAAGGCATTGGCTGAATTCTTGCTTAATCAAGAGGTGATTCA 
                   
               
               
                   
                 TCCCCGCGTTGCGCATGCCATCATGGAGGCAAGCTCTGTAGGTAGGAGA 
                   
               
               
                   
                 AAGCAAATTCAAGGGCTTGTTGACACAACAAACACCGTAATTAAGATTG 
                   
               
               
                   
                 CGCTTACTAGGAGGCCATTAGGCATCAAGAGGCTGATGCGGATAGTCA 
                   
               
               
                   
                 ATTATTCTAGCATGCATGCAATGCTGTTTAGAGACGATGTTTTTTCCTCC 
                   
               
               
                   
                 AGTAGATCCAACCACCCCTTAGTCTCTTCTAATATGTGTTCTCTGACACT 
                   
               
               
                   
                 GGCAGACTATGCACGGAATAGAAGCTGGTCACCTTTGACGGGAGGCAG 
                   
               
               
                   
                 GAAAATACTGGGTGTATCTAATCCTGATACGATAGAACTCGTAGAGGGT 
                   
               
               
                   
                 GAGATTCTTAGTGTAAGCGGAGGGTGTACAAGATGTGACAGCGGAGAT 
                   
               
               
                   
                 GAACAATTTACTTGGTTCCATCTTCCAAGCAATATAGAATTGACCGATG 
                   
               
               
                   
                 ACACCAGCAAGAATCCTCCGATGAGGGTACCATATCTCGGGTCAAAGA 
                   
               
               
                   
                 CACAGGAGAGGAGAGCTGCCTCACTTGCAAAAATAGCTCATATGTCGCC 
                   
               
               
                   
                 ACATGTAAAGGCTGCCCTAAGGGCATCATCCGTGTTGATCTGGGCTTAT 
                   
               
               
                   
                 GGGGATAATGAAGTAAATTGGACTGCTGCTCTTACGATTGCAAAATCTC 
                   
               
               
                   
                 GGTGTAATGTAAACTTAGAGTATCTTCGGTTACTGTCCCCTTTACCCACG 
                   
               
               
                   
                 GCTGGGAATCTTCAACATAGACTAGATGATGGTATAACTCAGATGACAT 
                   
               
               
                   
                 TCACCCCTGCATCTCTCTACAGGGTGTCACCTTACATTCACATATCCAAT 
                   
               
               
                   
                 GATTCTCAAAGGCTGTTCACTGAAGAAGGAGTCAAAGAGGGGAATGTG 
                   
               
               
                   
                 GTTTACCAACAGATCATGCTCTTGGGTTTATCTCTAATCGAATCGATCTT 
                   
               
               
                   
                 TCCAATGACAACAACCAGGACATATGATGAGATCACACTGCACCTACAT 
                   
               
               
                   
                 AGTAAATTTAGTTGCTGTATCAGAGAAGCACCTGTTGCGGTTCCTTTCG 
                   
               
               
                   
                 AGCTACTTGGGGTGGTACCGGAACTGAGGACAGTGACCTCAAATAAGTT 
                   
               
               
                   
                 TATGTATGATCCTAGCCCTGTATCGGAGGGAGACTTTGCGAGACTTGAC 
                   
               
               
                   
                 TTAGCTATCTTCAAGAGTTATGAGCTCAATCTGGAGTCATATCCCACGA 
                   
               
               
                   
                 TAGAGCTAATGAACATTCTTTCAATATCCAGCGGGAAGTTGATTGGCCA 
                   
               
               
                   
                 GTCTGTGGTTTCTTATGATGAAGATACCTCCATAAAGAATGACGCCATA 
                   
               
               
                   
                 ATAGTGTATGACAATACCCGAAATTGGATCAGTGAAGCTCAGAATTCAG 
                   
               
               
                   
                 ATGTGGTCCGCCTATTTGAATATGCAGCACTTGAAGTGCTCCTCGACTGT 
                   
               
               
                   
                 TCTTACCAACTCTATTACCTGAGAGTAAGAGGCCTAGACAATATTGTCT 
                   
               
               
                   
                 TATATATGGGTGATTTATACAAGAATATGCCAGGAATTCTACTTTCCAA 
                   
               
               
                   
                 CATTGCAGCTACAATATCTCATCCCGTCATTCATTCAAGGTTACATGCAG 
                   
               
               
                   
                 TGGGCCTGGTCAACCATGACGGATCACACCAACTTGCAGATACGGATTT 
                   
               
               
                   
                 TATCGAAATGTCTGCAAAACTATTAGTATCTTGCACCCGACGTGTGATC 
                   
               
               
                   
                 TCCGGCTTATATTCAGGAAATAAGTATGATCTGCTGTTCCCATCTGTCTT 
                   
               
               
                   
                 AGATGATAACCTGAATGAGAAGATGCTTCAGCTGATATCCCGGTTATGC 
                   
               
               
                   
                 TGTCTGTACACGGTACTCTTTGCTACAACAAGAGAAATCCCGAAAATAA 
                   
               
               
                   
                 GAGGCTTAACTGCAGAAGAGAAATGTTCAATACTCACTGAGTATTTACT 
                   
               
               
                   
                 GTCGGATGCTGTGAAACCATTACTTAGCCCCGATCAAGTGAGCTCTATC 
                   
               
               
                   
                 ATGTCTCCTAACATAATTACATTCCCAGCTAATCTGTACTACATGTCTCG 
                   
               
               
                   
                 GAAGAGCCTCAATTTGATCAGGGAAAGGGAGGACAGGGATACTATCCT 
                   
               
               
                   
                 GGCGTTGTTGTTCCCCCAAGAGCCATTATTAGAGTTCCCTTCTGTGCAAG 
                   
               
               
                   
                 ATATTGGTGCTCGAGTGAAAGATCCATTCACCCGACAACCTGCGGCATT 
                   
               
               
                   
                 TTTGCAAGAGTTAGATTTGAGTGCTCCAGCAAGGTATGACGCATTCACA 
                   
               
               
                   
                 CTTAGTCAGATTCATCCTGAACTCACATCTCCAAATCCGGAGGAAGACC 
                   
               
               
                   
                 ACTTAGTACGATACTTGTTCAGAGGGATAGGGACTGCATCTTCCTCTTG 
                   
               
               
                   
                 GTATAAGGCATCTCATCTCCTTTCTGTACCCGAGGTAAGATGTGCAAGA 
                   
               
               
                   
                 CACGGGAACTCCTTATACTTAGCTGAAGGGAGCGGAGCCATCATGAGTC 
                   
               
               
                   
                 TTCTCGAACTGCATGTACCACATGAAACTATCTATTACAATACGCTCTTT 
                   
               
               
                   
                 TCAAATGAGATGAACCCCCCGCAACGACATTTCGGGCCGACCCCAACTC 
                   
               
               
                   
                 AGTTTTTGAATTCGGTTGTTTATAGGAATCTACAGGCGGAGGTAACATG 
                   
               
               
                   
                 CAAAGATGGATTTGTCCAAGAGTTCCGTCCATTATGGAGAGAAAATACA 
                   
               
               
                   
                 GAGGAAAGTGACCTGACCTCAGATAAAGCAGTGGGGTATATTACATCT 
                   
               
               
                   
                 GCAGTGCCCTACAGATCTGTATCATTGCTGCATTGTGACATTGAAATTCC 
                   
               
               
                   
                 TCCAGGGTCCAATCAAAGCTTACTAGATCAACTAGCTATCAATTTATCT 
                   
               
               
                   
                 CTGATTGCCATGCATTCTGTAAGGGAGGGCGGGGTAGTAATCATCAAAG 
                   
               
               
                   
                 TGTTGTATGCAATGGGATACTACTTTCATCTACTCATGAACTTGTTTGCT 
                   
               
               
                   
                 CCGTGTTCCACAAAAGGATATATTCTCTCTAATGGTTATGCATGTCGAG 
                   
               
               
                   
                 GAGATATGGAGTGTTACCTGGTATTTGTCATGGGTTACCTGGGCGGGCC 
                   
               
               
                   
                 TACATTTGTACATGAGGTGGTGAGGATGGCAAAAACTCTGGTGCAGCGG 
                   
               
               
                   
                 CACGGTACGCTTTTGTCTAAATCAGATGAGATCACACTGACCAGGTTAT 
                   
               
               
                   
                 TCACCTCACAGCGGCAGCGTGTGACAGACATCCTATCCAGTCCTTTACC 
                   
               
               
                   
                 AAGATTAATAAAGTACTTGAGGAAGAAATTGACACTGCGCTGATTGAA 
                   
               
               
                   
                 GCCGGGGGACAGCCCGTCCGTCCATTCTGTGCGGAGAGTCTGGTGAGCA 
                   
               
               
                   
                 CGCTAGCGAACATAACTCAGATAACCCAGATCATCGCTAGCCACATTGA 
                   
               
               
                   
                 CACAGTTATCCGGTCTGTGATATATATGGAAGCTGAGGGTGATCTCGCT 
                   
               
               
                   
                 GACACAGTATTTCTATTTACCCCTTACAATCTCTCTACTGACGGGAAAA 
                   
               
               
                   
                 AGAGGACATCACTTAAACAGTGCACGAGACAGATCCTAGAGGTTACAA 
                   
               
               
                   
                 TACTAGGTCTTAGAGTCGAAAATCTCAATAAAATAGGCGATATAATCAG 
                   
               
               
                   
                 CCTAGTGCTTAAAGGCATGATCTCCATGGAGGACCTTATCCCACTAAGG 
                   
               
               
                   
                 ACATACTTGAAGCATAGTACCTGCCCTAAATATTTGAAGGCTGTCCTAG 
                   
               
               
                   
                 GTATTACCAAACTCAAAGAAATGTTTACAGACACTTCTGTACTGTACTT 
                   
               
               
                   
                 GACTCGTGCTCAACAAAAATTCTACATGAAAACTATAGGCAATGCAGTC 
                   
               
               
                   
                 AAAGGATATTACAGTAACTGTGACTCTTAACGAAAATCACATATTAATA 
                   
               
               
                   
                 GGCTCCTTTTTTGGCCAATTGTATTCTTGTTGATTTAATCATATTATGTTA 
                   
               
               
                   
                 GAAAAAAGTTGAACCCTGACTCCTTAGGACTCGAATTCGAACTCAAATA 
                   
               
               
                   
                 AATGTCTTAAAAAAAGGTTGCGCACAATTATTCTTGAGTGTAGTCTCGT 
                   
               
               
                   
                 CATTCACCAAATCTTTGTTTGGT 
                   
               
               
                 Sequence 
                 
                   accaaacagagaatccgtgagttacgataaaaggcgaaggagcaattgaagtcgcacgggtagaaggt 
                 
                 84 
               
               
                 NDV LaSota 
                 
                   gtgaatctcgagtgcgagcccgaagcacaaactcgagaaagccttctgccaacatgtcttccgtatttgat 
                 
                   
               
               
                 L289A 
                 
                   gagtacgaacagctcctcgcggctcagactcgccccaatggagctcatggagggggagaaaaagggagt 
                 
                   
               
               
                 genome 
                 
                   accttaaaagtagacgtcccggtattcactcttaacagtgatgacccagaagatagatggagctttgtggt 
                 
                   
               
               
                 (Mutation 
                 
                   attctgcctccggattgctgttagcgaagatgccaacaaaccactcaggcaaggtgctctcatatctctttt 
                 
                   
               
               
                 L289A in the 
                 
                   atgctcccactcacaggtaatgaggaaccatgttgccCttgcagggaaacagaatgaagccacattggcc 
                 
                   
               
               
                 F protein. 
                 
                   gtgcttgagattgatggctttgccaacggcacgccccagttcaacaataggagtggagtgtctgaagaga 
                 
                   
               
               
                 CTA = Leu 
                 
                   gagcacagagatttgcgatgatagcaggatctctccctcgggcatgcagcaacggaaccccgttcgtcac 
                 
                   
               
               
                 changed to 
                 
                   agccggggcCgaagatgatgcaccagaagacatcaccgataccctggagaggatcctctctatccaggc 
                 
                   
               
               
                 GCC = Ala 
                 
                   tcaagtatgggtcacagtagcaaaagccatgactgcgtatgagactgcagatgagtcggaaacaaggcg 
                 
                   
               
               
                 (underlined 
                 
                   aatcaataagtatatgcagcaaggcagggtccaaaagaaatacatcctctaccccgtatgcaggagcac 
                 
                   
               
               
                 and bold). 
                 
                   aatccaactcacgatcagacagtctcttgcagtccgcatctttttggttagcgagctcaagagaggccgca 
                 
                   
               
               
                 Unique 
                 
                   acacggcaggtggtacctctacttattataacctggtaggggacgtagactcatacatcaggaataccgg 
                 
                   
               
               
                 restriction 
                 
                   gcttactgcattcttcttgacactcaagtacggaatcaacaccaagacatcagcccttgcacttagtagcct 
                 
                   
               
               
                 site Sac II 
                 
                   ctcaggcgacatccagaagatgaagcagctcatgcgtttgtatcggatgaaaggagataatgcgccgtac 
                 
                   
               
               
                 (CCGCGG) 
                 
                   atgacattacttggtgatagtgaccagatgagctttgcgcctgccgagtatgcacaactttactcctttgcc 
                 
                   
               
               
                 for insertion 
                 
                   atgggtatggcatcagtcctagataaaggtactgggaaataccaatttgccagggactttatgagcacatc 
                 
                   
               
               
                 of foreign 
                 
                   attctggagacttggagtagagtacgctcaggctcagggaagtagcattaacgaggatatggctgccgag 
                 
                   
               
               
                 genes double 
                 
                   ctaaagctaaccccagcagcaaGgaGgggcctggcagctgctgcccaacgggtctccgaGgaGacca 
                 
                   
               
               
                 underlined.) 
                 
                   gcagcataGacatgcctactcaacaagtcggagtcctcactgggcttagcgagggggggtcccaagctct 
                 
                   
               
               
                   
                 
                   acaaggcggatcgaatagatcgcaagggcaaccagaagccggggatggggagacccaattcctggatc 
                 
                   
               
               
                   
                 
                   tgatgagagcggtagcaaatagcatgagggaggcgccaaactctgcacagggcactccccaatcggggc 
                 
                   
               
               
                   
                 
                   ctcccccaactcctgggccatcccaagataacgacaccgactgggggtattgatggacaaaacccagcct 
                 
                   
               
               
                   
                 
                   gcttccacaaaaacatcccaatgccctcacccgtagtcgacccctcgatttgcggctctatatgaccacacc 
                 
                   
               
               
                   
                 
                   ctcaaacaaacatccccctctttcctccctccccctgctgtacaactAcgTacgccctagataccacaggc 
                 
                   
               
               
                   
                 
                   acaatgcggctcactaacaatcaaaacagagccgagggaattagaaaaaagtacgggtagaagaggg 
                 
                   
               
               
                   
                 
                   atattcagagatcagggcaagtctcccgagtctctgctctctcctctacctgatagaccaggacaaacatg 
                 
                   
               
               
                   
                 
                   gccacctttacagatgcagagatcgacgagctatttgagacaagtggaactgtcattgacaacataattac 
                 
                   
               
               
                   
                 
                   agcccagggtaaaccagcagagactgttggaaggagtgcaatcccacaaggcaagaccaaggtgctga 
                 
                   
               
               
                   
                 
                   gcgcagcatgggagaagcatgggagcatccagccaccggccagtcaagacaaccccgatcgacaggac 
                 
                   
               
               
                   
                 
                   agatctgacaaacaaccatccacacccgagcaaacgaccccgcatgacagcccgccggccacatccgcc 
                 
                   
               
               
                   
                 
                   gaccagccccccacccaggccacagacgaagccgtcgacacacagCtcaggaccggagcaagcaactc 
                 
                   
               
               
                   
                 
                   tctgctgttgatgcttgacaagctcagcaataaatcgtccaatgctaaaaagggcccatggtcgagccccc 
                 
                   
               
               
                   
                 
                   aagaggggaatcaccaacgtccgactcaacagcaggggagtcaacccagtcgcggaaacagtcaggaa 
                 
                   
               
               
                   
                 
                   agaccgcagaaccaagtcaaggccgcccctggaaaccagggcacagacgtgaacacagcatatcatgg 
                 
                   
               
               
                   
                 
                   acaatgggaggagtcacaactatcagctggtgcaacccctcatgctctccgatcaaggcagagccaaga 
                 
                   
               
               
                   
                 
                   caatacccttgtatctgcggatcatgtccagccacctgtagactttgtgcaagcgatgatgtctatgatgga 
                 
                   
               
               
                   
                 
                   ggcgatatcacagagagtaagtaaggttgactatcagctagatcttgtcttgaaacagacatcctccatcc 
                 
                   
               
               
                   
                 
                   ctatgatgcggtccgaaatccaacagctgaaaacatctgttgcagtcatggaagccaacttgggaatgat 
                 
                   
               
               
                   
                 
                   gaagattctggatcccggttgtgccaacatttcatctctgagtgatctacgggcagttgcccgatctcaccc 
                 
                   
               
               
                   
                 
                   ggttttagtttcaggccctggagacccctctccctatgtgacacaaggaggcgaaatggcacttaataaac 
                 
                   
               
               
                   
                 
                   tttcgcaaccagtgccacatccatctgaattgattaaacccgccactgcatgcgggcctgatataggagtg 
                 
                   
               
               
                   
                 
                   gaaaaggacactgtccgtgcattgatcatgtcacgcccaatgcacccgagttcttcagccaagctcctaag 
                 
                   
               
               
                   
                 
                   caagttagatgcagccgggtcgatcgaggaaatcaggaaaatcaagcgccttgctctaaatggctaatta 
                 
                   
               
               
                   
                 
                   ctactgccacacgtagcgggtccctgtccactcggcatcacacggaatctgcaccgagttccccc 
                   
                     ccgcGg 
                   
                 
                   
               
               
                   
                 
                   acccaaggtccaactctccaagcggcaatcctctctcgcttcctcagccccactgaatgAtcgcgtaaccg 
                 
                   
               
               
                   
                 
                   taattaatctagctacatttaagattaagaaaaaatacgggtagaattggagtgccccaattgtgccaaga 
                 
                   
               
               
                   
                 
                   tggactgatagtaaggaggactcagtattcatcaccacctatggattcatctttcaagttgggaatggaga 
                 
                   
               
               
                   
                 
                   gtcctacaagAcacaggagatgggaagaagcaaatcgccccgcaatataggatccagcgccttgacttg 
                 
                   
               
               
                   
                 
                   tggactgatagtaaggaggactcagtattcatcaccacctatggattcatctttcaagttgggaatgaaga 
                 
                   
               
               
                   
                 
                   agccacCgtcggcatgatcgatgataaacccaagcgcgagttactttccgctgcgatgctctgcctagga 
                 
                   
               
               
                   
                 
                   agcgtcccaaataccggagaccttattgagctggcaagggcctgtctcactatgatagtcacatgcaaga 
                 
                   
               
               
                   
                 
                   agagtgcaactaatactgagagaatggttttctcagtagtgcaggcaccccaagtgctgcaaagctgtag 
                 
                   
               
               
                   
                 
                   ggttgtggcaaacaaatactcatcagtgaatgcagtcaagcacgtgaaagcgccagagaagattcccgg 
                 
                   
               
               
                   
                 
                   gagtggaaccctagaatacaaggtgaactttgtctccttgactgtggtaccgaagaGggatgtctacaag 
                 
                   
               
               
                   
                 
                   atcccagctgcagtattgaaggtttctggctcgagtctgtacaatcttgcgctcaatgtcactattaatgtgg 
                 
                   
               
               
                   
                 
                   aggtagacccgaggagtcctttggttaaatctCtgtctaagtctgacagcggatactatgctaacctcttct 
                 
                   
               
               
                   
                 
                   tgcatattggacttatgaccacTgtagataggaaggggaagaaagtgacatttgacaagctggaaaaga 
                 
                   
               
               
                   
                 
                   aaataaggagccttgatctatctgtcgggctcagtgatgtgctcgggccttccgtgttggtaaaagcaaga 
                 
                   
               
               
                   
                 
                   ggtgcacggactaagcttttggcacctttcttctctagcagtgggacagcctgctatcccatagcaaatgct 
                 
                   
               
               
                   
                 
                   tctcctcaggtggccaagatactctggagtcaaaccgcgtgcctgcggagcgttaaaatcattatccaagc 
                 
                   
               
               
                   
                 
                   aggtacccaacgcgctgtcgcagtgaccgccgaccacgaggttacctctactaagctggagaaggggca 
                 
                   
               
               
                   
                 
                   cacccttgccaaatacaatccttttaagaaataagctgcgtctctgagattgcgctccgcccactcacccag 
                 
                   
               
               
                   
                 
                   atcatcatgacacaaaaaactaatctgtcttgattatttacagttagtttacctgtctatcaagttagaaaa 
                 
                   
               
               
                   
                 
                   aacacgggtagaagattctggatcccggttggcgccctccaggtgcaagatgggctccagaccttctacc 
                 
                   
               
               
                   
                 
                   aagaacccagcacctatgatgctgactatccgggttgcgctggtactgagttgcatctgtccggcaaactc 
                 
                   
               
               
                   
                 
                   cattgatggcaggcctcttgcagctgcaggaattgtggttacaggagacaaagccgtcaacatatacacct 
                 
                   
               
               
                   
                 
                   catcccagacaggatcaatcatagttaagctcctcccgaatctgcccaaggataaggaggcatgtgcgaa 
                 
                   
               
               
                   
                 
                   agcccccttggatgcatacaacaggacattgaccactttgctcaccccccttggtgactctatccgtaggat 
                 
                   
               
               
                   
                 
                   acaagagtctgtgactacatctggaggggggagacaggggcgccttataggcgccattattggcggtgtg 
                 
                   
               
               
                   
                 
                   gctcttggggttgcaactgccgcacaaataacagcggccgcagctctgatacaagccaaacaaaatgctg 
                 
                   
               
               
                   
                 
                   ccaacatcctccgacttaaagagagcattgccgcaaccaatgaggctgtgcatgaggtcactgacggatt 
                 
                   
               
               
                   
                 
                   atcgcaactagcagtggcagttgggaagatgcagcagtttgttaatgaccaatttaataaaacagctcag 
                 
                   
               
               
                   
                 
                   gaattagactgcatcaaaattgcacagcaagttggtgtagagctcaacctgtacctaaccgaattgactac 
                 
                   
               
               
                   
                 
                   agtattcggaccacaaatcacttcacctgctttaaacaagctgactattcaggcactttacaatctagctgg 
                 
                   
               
               
                   
                 
                   tggaaatatggattacttattgactaagttaggtgtagggaacaatcaactcagctcattaatcggtagcg 
                 
                   
               
               
                   
                 
                   gcttaatcaccggtaaccctattctatacgactcacagactcaactcttgggtatacaggtaactGCCcct 
                 
                   
               
               
                   
                 
                   tcagtcgggaacctaaataatatgcgtgccacctacttggaaaccttatccgtaagcacaaccaggggatt 
                 
                   
               
               
                   
                 
                   tgcctcggcacttgtcccAaaagtggtgacacaggtcggttctgtgatagaagaacttgacacctcatact 
                 
                   
               
               
                   
                 
                   gtatagaaactgacttagatttatattgtacaagaatagtaacgttccctatgtcccctggtatttattcctg 
                 
                   
               
               
                   
                 
                   cttgagcggcaatacgtcggcctgtatgtactcaaagaccgaaggcgcacttactacaccatacatgacta 
                 
                   
               
               
                   
                 
                   tcaaaggttcagtcatcgccaactgcaagatgacaacatgtagatgtgtaaaccccccgggtatcatatcg 
                 
                   
               
               
                   
                 
                   caaaactatggagaagccgtgtctctaatagataaacaatcatgcaatgttttatccttaggcgggataac 
                 
                   
               
               
                   
                 
                   tttaaggctcagtggggaattcgatgtaacttatcagaagaatatctcaatacaagattctcaagtaataa 
                 
                   
               
               
                   
                 
                   taacaggcaatcttgatatctcaactgagcttgggaatgtcaacaactcgatcagtaatgctttgaataagt 
                 
                   
               
               
                   
                 
                   tagaggaaagcaacagaaaactagacaaagtcaatgtcaaactgactagcacatctgctctcattaccta 
                 
                   
               
               
                   
                 
                   tatcgttttgactatcatatctcttgtttttggtatacttagcctgattctagcatgctacctaatgtacaag 
                 
                   
               
               
                   
                 
                   caaaaggcgcaacaaaagaccttattatggcttgggaataatactctagatcagatgagagccactacaaa 
                 
                   
               
               
                   
                 
                   aatgtgaacacagatgaggaacgaaggtttccctaatagtaatttgtgtgaaagttctggtagtctgtcag 
                 
                   
               
               
                   
                 
                   ttcagagagttaagaaaaaactaccggttgtagatgaccaaaggacgatatacgggtagaacggtaaga 
                 
                   
               
               
                   
                 
                   gaggccgcccctcaattgcgagccaggcttcacaacctccgttctaccgcttcaccgacaacagtcctcaa 
                 
                   
               
               
                   
                 
                   tcatggaccgcgccgttagccaagttgcgttagagaatgatgaaagagaggcaaaaaatacatggcgctt 
                 
                   
               
               
                   
                 
                   gatattccggattgcaatcttattcttaacagtagtgaccttggctatatctgtagcctcccttttatatag 
                 
                   
               
               
                   
                 
                   catgggggctagcacacctagcgatcttgtaggcataccgactaggatttccagggcagaagaaaagattac 
                 
                   
               
               
                   
                 
                   atctacacttggttccaatcaagatgtagtagataggatatataagcaagtggcccttgagtctccgttggc 
                 
                   
               
               
                   
                 
                   attgttaaatactgagaccacaattatgaacgcaataacatctctctcttatcagattaatggagctgcaaa 
                 
                   
               
               
                   
                 
                   caacagtgggtggggggcacctatccatgacccagattatataggggggataggcaaagaactcattgta 
                 
                   
               
               
                   
                 
                   gatgatgctagtgatgtcacatcattctatccctctgcatttcaagaacatctgaattttatcccggcgccta 
                 
                   
               
               
                   
                 
                   ctacaggatcaggttgcactcgaataccctcatttgacatgagtgctacccattactgctacacccataatg 
                 
                   
               
               
                   
                 
                   taatattgtctggatgcagagatcactcacattcatatcagtatttagcacttggtgtgctccggacatctgc 
                 
                   
               
               
                   
                 
                   aacagggagggtattcttttctactctgcgttccatcaacctggacgacacccaaaatcggaagtcttgca 
                 
                   
               
               
                   
                 
                   gtgtgagtgcaactcccctgggttgtgatatgctgtgctcgaaagtcacggagacagaggaagaagatta 
                 
                   
               
               
                   
                 
                   taactcagctgtccctacgcggatggtacatgggaggttagggttcgacggccagtaccacgaaaaggac 
                 
                   
               
               
                   
                 
                   ctagatgtcacaacattattcggggactgggtggccaactacccaggagtagggggtggatcttttattga 
                 
                   
               
               
                   
                 
                   cagccgcgtatggttctcagtctacggagggttaaaacccaattcacccagtgacactgtacaggaaggg 
                 
                   
               
               
                   
                 
                   aaatatgtgatatacaagcgatacaatgacacatgcccagatgagcaagactaccagattcgaatggcc 
                 
                   
               
               
                   
                 
                   aagtcttcgtataagcctggacggtttggtgggaaacgcatacagcaggctatcttatctatcaaggtgtc 
                 
                   
               
               
                   
                 
                   aacatccttaggcgaagacccggtactgactgtaccgcccaacacagtcacactcatgggggccgaagg 
                 
                   
               
               
                   
                 
                   cagaattctcacagtagggacatctcatttcttgtatcaacgagggtcatcatacttctctcccgcgttatta 
                 
                   
               
               
                   
                 
                   tatcctatgacagtcagcaacaaaacagccactcttcatagtccttatacattcaatgccttcactcggcca 
                 
                   
               
               
                   
                 
                   ggtagtatcccttgccaggcttcagcaagatgccccaactcgtgtgttactggagtctatacagatccatat 
                 
                   
               
               
                   
                 
                   cccctaatcttctatagaaaccacaccttgcgaggggtattcgggacaatgcttgatggtgtacaagcaag 
                 
                   
               
               
                   
                 
                   acttaaccctgcgtctgcagtattcgatagcacatcccgcagtcgcattactcgagtgagttcaagcagtac 
                 
                   
               
               
                   
                 
                   caaagcagcatacacaacatcaacttgttttaaagtggtcaagactaataagacctattgtctcagcattg 
                 
                   
               
               
                   
                 
                   ctgaaatatctaatactctcttcggagaattcagaatcgtcccgttactagttgagatcctcaaagatgacg 
                 
                   
               
               
                   
                 
                   gggttagagaagccaggtctggctagttgagtcaattataaaggagttggaaagatggcattgtatcacct 
                 
                   
               
               
                   
                 
                   atcttctgcgacatcaagaatcaaaccgaatgccggcgcgtgctcgaattccatgttgccagttgaccaca 
                 
                   
               
               
                   
                 
                   atcagccagtgctcatgcgatcagattaagccttgtcaAtaGtctcttgattaagaaaaaatgtaagtggc 
                 
                   
               
               
                   
                 
                   aatgagatacaaggcaaaacagctcatggtTaaCaatacgggtaggacatggcgagctccggtcctga 
                 
                   
               
               
                   
                 
                   aagggcagagcatcagattatcctaccagagTcacacctgtcttcaccattggtcaagcacaaactactct 
                 
                   
               
               
                   
                 
                   attactggaaattaactgggctaccgcttcctgatgaatgtgacttcgaccacctcattctcagccgacaat 
                 
                   
               
               
                   
                 
                   ggaaaaaaatacttgaatcggcctctcctgatactgagagaatgataaaactcggaagggcagtacacc 
                 
                   
               
               
                   
                 
                   aaactcttaaccacaattccagaataaccggagtgctccaccccaggtgtttagaaGaactggctaatatt 
                 
                   
               
               
                   
                 
                   gaggtcccagattcaaccaacaaatttcggaagattgagaagaagatccaaattcacaacacgagatat 
                 
                   
               
               
                   
                 
                   ggagaactgttcacaaggctgtgtacgcatatagagaagaaactgctggggtcatcttggtctaacaatgt 
                 
                   
               
               
                   
                 
                   cccccggtcagaggagttcagcagcattcgtacggatccggcattctggtttcactcaaaatggtccacag 
                 
                   
               
               
                   
                 
                   ccaagtttgcatggctccatataaaacagatccagaggcatctgatggtggcagctaGgacaaggtctgc 
                 
                   
               
               
                   
                 
                   ggccaacaaattggtgatgctaacccataaggtaggccaagtctttgtcactcctgaacttgtcgttgtgac 
                 
                   
               
               
                   
                 
                   gcatacgaatgagaacaagttcacatgtcttacccaggaacttgtattgatgtatgcagatatgatggagg 
                 
                   
               
               
                   
                 
                   gcagagatatggtcaacataatatcaaccacggcggtgcatctcagaagcttatcagagaaaattgatga 
                 
                   
               
               
                   
                 
                   cattttgcggttaatagacgctctggcaaaagacttgggtaatcaagtctacgatgttgtatcactaatgga 
                 
                   
               
               
                   
                 
                   gggatttgcatacggagctgtccagctactcgagccgtcaggtacatttgcaggagatttcttcgcattcaa 
                 
                   
               
               
                   
                 
                   cctgcaggagcttaaagacattctaattggcctcctccccaatgatatagcagaatccgtgactcatgcaa 
                 
                   
               
               
                   
                 
                   tcgctactgtattctctggtttagaacagaatcaagcagctgagatgttgtgtctgttgcgtctgtggggtca 
                 
                   
               
               
                   
                 
                   cccactgcttgagtcccgtattgcagcaaaggcagtcaggagccaaatgtgcgcaccgaaaatggtagac 
                 
                   
               
               
                   
                 
                   tttgatatgatccttcaggtactgtctttcttcaagggaacaatcatcaacgggtacagaaagaagaatgc 
                 
                   
               
               
                   
                 
                   aggtgtgtggccgcgagtcaaagtggatacaatatatgggaaggtcattgggcaactacatgcagattca 
                 
                   
               
               
                   
                 
                   gcagagatttcacacgatatcatgttgagagagtataagagtttatctgcacttgaatttgagccatgtata 
                 
                   
               
               
                   
                 
                   gaatatgaccctgtcaccaacctgagcatgttcctaaaagacaaggcaatcgcacaccccaacgataatt 
                 
                   
               
               
                   
                 
                   ggcttgcctcgtttaggcggaaccttctctccgaagaccagaagaaacatgtaaaagaagcaacttcgac 
                 
                   
               
               
                   
                 
                   taatcgcctcttgatagagtttttagagtcaaatgattttgatccatataaagagatggaatatctgacgac 
                 
                   
               
               
                   
                 
                   ccttgagtaccttagagatgacaatgtggcagtatcatactcgctcaaggagaaggaagtgaaagttaat 
                 
                   
               
               
                   
                 
                   ggacggatcttcgctaagctgacaaagaagttaaggaactgtcaggtgatggcggaagggatcctagcc 
                 
                   
               
               
                   
                 
                   gatcagattgcacctttctttcagggaaatggagtcattcaggatagcatatccttgaccaagagtatgcta 
                 
                   
               
               
                   
                 
                   gcgatgagtcaactgtcttttaacagcaataagaaacgtatcactgactgtaaagaaagagtatcttcaa 
                 
                   
               
               
                   
                 
                   accgcaatcatgatccgaaaagcaagaaccgtcggagagttgcaaccttcataacaactgacctgcaaa 
                 
                   
               
               
                   
                 
                   agtactgtcttaattggagatatcagacaatcaaattgttcgctcatgccatcaatcagttgatgggcctac 
                 
                   
               
               
                   
                 
                   ctcacttcttcgaatggattcacctaagactgatggacactacgatgttcgtaggagaccctttcaatcctc 
                 
                   
               
               
                   
                 
                   caagtgaccctactgactgtgacctctcaagagtccctaatgatgacatatatattgtcagtgccagaggg 
                 
                   
               
               
                   
                 
                   ggtatcgaaggattatgccagaagctatggacaatgatctcaattgctgcaatccaacttgctgcagctag 
                 
                   
               
               
                   
                 
                   atcgcattgtcgtgttgcctgtatggtacagggtgataatcaagtaatagcagtaacgagagaggtaagat 
                 
                   
               
               
                   
                 
                   cagacgactctccggagatggtgttgacacagttgcatcaagccagtgataatttcttcaaggaattaatt 
                 
                   
               
               
                   
                 
                   catgtcaatcatttgattggccataatttgaaggatcgtgaaaccatcaggtcagacacattcttcatatac 
                 
                   
               
               
                   
                 
                   agcaaacgaatcttcaaagatggagcaatcctcagtcaagtcctcaaaaattcatctaaattagtgctagt 
                 
                   
               
               
                   
                 
                   gtcaggtgatctcagtgaaaacaccgtaatgtcctgtgccaacattgcctctactgtagcacggctatgcg 
                 
                   
               
               
                   
                 
                   agaacgggcttcccaaagacttctgttactatttaaactatataatgagttgtgtgcagacatactttgactc 
                 
                   
               
               
                   
                 
                   tgagttctccatcaccaacaattcgcaccccgatcttaatcagtcgtggattgaggacatctcttttgtgcac 
                 
                   
               
               
                   
                 
                   tcatatgttctgactcctgcccaattagggggactgagtaaccttcaatactcaaggctctacactagaaat 
                 
                   
               
               
                   
                 
                   atcggtgacccggggactactgcttttgcagagatcaagcgactagaagcagtgggattactgagtccta 
                 
                   
               
               
                   
                 
                   acattatgactaatatcttaactaggccgcctgggaatggagattgggccagtctgtgcaacgacccatac 
                 
                   
               
               
                   
                 
                   tctttcaattttgagactgttgcaagcccaaatattgttcttaagaaacatacgcaaagagtcctatttgaa 
                 
                   
               
               
                   
                 
                   acttgttcaaatcccttattgtctggagtgcacacagaggataatgaggcagaagagaaggcattggctg 
                 
                   
               
               
                   
                 
                   aattcttgcttaatcaagaggtgattcatccccgcgttgcgcatgccatcatggaggcaagctctgtaggta 
                 
                   
               
               
                   
                 
                   ggagaaagcaaattcaagggcttgttgacacaacaaacaccgtaattaagattgcgcttactaggaggcc 
                 
                   
               
               
                   
                 
                   attaggcatcaagaggctgatgcggatagtcaattattctagcatgcatgcaatgctgtttagagacgatg 
                 
                   
               
               
                   
                 
                   ttttttcctccagtagatccaaccaccccttagtctcttctaatatgtgttctctgacactggcagactatg 
                 
                   
               
               
                   
                 
                   cacggaatagaagctggtcacctttgacgggaggcaggaaaatactgggtgtatctaatcctgatacgatag 
                 
                   
               
               
                   
                 
                   aactcgtagagggtgagattcttagtgtaagcggagggtgtacaagatgtgacagcggagatgaacaatt 
                 
                   
               
               
                   
                 
                   tacttggttccatcttccaagcaatatagaattgaccgatgacaccagcaagaatcctccgatgagggtac 
                 
                   
               
               
                   
                 
                   catatctcgggtcaaagacacaggagaggagagctgcctcacttgcaaaaatagctcatatgtcgccaca 
                 
                   
               
               
                   
                 
                   tgtaaaggctgccctaagggcatcatccgtgttgatctgggcttatggggataatgaagtaaattggactg 
                 
                   
               
               
                   
                 
                   ctgctcttacgattgcaaaatctcggtgtaatgtaaacttagagtatcttcggttactgtcccctttacccac 
                 
                   
               
               
                   
                 
                   ggctgggaatcttcaacatagactagatgatggtataactcagatgacattcacccctgcatctctctaca 
                 
                   
               
               
                   
                 
                   ggGtgtcaccttacattcacatatccaatgattctcaaaggctgttcactgaagaaggagtcaaagaggg 
                 
                   
               
               
                   
                 
                   gaatgtggtttaccaacagatcatgctcttgggtttatctctaatcgaatcgatctttccaatgacaacaacc 
                 
                   
               
               
                   
                 
                   aggacatatgatgagatcacactgcacctacatagtaaatttagttgctgtatcagagaagcacctgttgc 
                 
                   
               
               
                   
                 
                   ggttcctttcgagctacttggggtggtaccggaactgaggacagtgacctcaaataagtttatgtatgatcc 
                 
                   
               
               
                   
                 
                   tagccctgtatcggagggagactttgcgagacttgacttagctatcttcaagagttatgagcttaatctgga 
                 
                   
               
               
                   
                 
                   gtcatatcccacgatagagctaatgaacattctttcaatatccagcgggaagttgattggccagtctgtggt 
                 
                   
               
               
                   
                 
                   ttcttatgatgaagatacctccataaagaatgacgccataatagtgtatgacaatacccgaaattggatca 
                 
                   
               
               
                   
                 
                   gtgaagctcagaattcagatgtggtccgcctatttgaatatgcagcacttgaagtgctcctcgactgttctta 
                 
                   
               
               
                   
                 
                   ccaactctattacctgagagtaagaggcctGgacaatattgtcttatatatgggtgatttatacaagaatat 
                 
                   
               
               
                   
                 
                   gccaggaattctactttccaacattgcagctacaatatctcatcccgtcattcattcaaggttacatgcagtg 
                 
                   
               
               
                   
                 
                   ggcctggtcaaccatgacggatcacaccaacttgcagatacggattttatcgaaatgtctgcaaaactatt 
                 
                   
               
               
                   
                 
                   agtatcttgcacccgacgtgtgatctccggcttatattcaggaaataagtatgatctgctgttcccatctgtc 
                 
                   
               
               
                   
                 
                   ttagatgataacctgaatgagaagatgcttcagctgatatcccggttatgctgtctgtacacggtactctttg 
                 
                   
               
               
                   
                 
                   ctacaacaagagaaatcccgaaaataagaggcttaactgcagaagagaaatgttcaatactcactgagt 
                 
                   
               
               
                   
                 
                   atttactgtcggatgctgtgaaaccattacttagccccgatcaagtgagctctatcatgtctcctaacataat 
                 
                   
               
               
                   
                 
                   tacattcccagctaatctgtactacatgtctcggaagagcctcaatttgatcagggaaagggaggacagg 
                 
                   
               
               
                   
                 
                   gatactatcctggcgttgttgttcccccaagagccattattagagttcccttctgtgcaagatattggtgctc 
                 
                   
               
               
                   
                 
                   gagtgaaagatccattcacccgacaacctgcggcatttttgcaagagttagatttgagtgctccagcaagg 
                 
                   
               
               
                   
                 
                   tatgacgcattcacacttagtcagattcatcctgaactcacatctccaaatccggaggaagactacttagta 
                 
                   
               
               
                   
                 
                   cgatacttgttcagagggatagggactgcatcttcctcttggtataaggcatctcatctcctttctgtacccg 
                 
                   
               
               
                   
                 
                   aggtaagatgtgcaagacacgggaactccttatacttagctgaagggagcggagccatcatgagtcttct 
                 
                   
               
               
                   
                 
                   cgaactgcatgtaccacatgaaactatctattacaatacgctcttttcaaatgagatgaaccccccgcaac 
                 
                   
               
               
                   
                 
                   gacatttcgggccgaccccaactcagtttttgaattcggttgtttataggaatctacaggcggaggtaacat 
                 
                   
               
               
                   
                 
                   gcaaagatggatttgtccaagagttccgtccattatggagagaaaatacagaggaaagCgacctgacct 
                 
                   
               
               
                   
                 
                   cagataaagTagtggggtatattacatctgcagtgccctacagatctgtatcattgctgcattgtgacattg 
                 
                   
               
               
                   
                 
                   aaattcctccagggtccaatcaaagcttactagatcaactagctatcaatttatctctgattgccatgcattc 
                 
                   
               
               
                   
                 
                   tgtaagggagggcggggtagtaatcatcaaagtgttgtatgcaatgggatactactttcatctactcatga 
                 
                   
               
               
                   
                 
                   acttgtttgctccgtgttccacaaaaggatatattctctctaatggttatgcatgtcgaggagatatggagtg 
                 
                   
               
               
                   
                 
                   ttacctggtatttgtcatgggttacctgggcgggcctacatttgtacatgaggtggtgaggatggcGaaaa 
                 
                   
               
               
                   
                 
                   ctctggtgcagcggcacggtacgctTttgtctaaatcagatgagatcacactgaccaggttattcacctca 
                 
                   
               
               
                   
                 
                   cagcggcagcgtgtgacagacatcctatccagtcctttaccaagattaataaagtacttgaggaagaatat 
                 
                   
               
               
                   
                 
                   tgacactgcgctgattgaagccgggggacagcccgtccgtccattctgtgcggagagtctggtgagcacg 
                 
                   
               
               
                   
                 
                   ctagcgaacataactcagataacccagatCatcgctagtcacattgacacagttatccggtctgtgatata 
                 
                   
               
               
                   
                 
                   tatggaagctgagggtgatctcgctgacacagtatttctatttaccccttacaatctctctactgacgggaa 
                 
                   
               
               
                   
                 
                   aaagaggacatcacttaAacagtgcacgagacagatcctagaggttacaatactaggtcttagagtcga 
                 
                   
               
               
                   
                 
                   aaatctcaataaaataggcgatataatcagcctagtgcttaaaggcatgatctccatggaggaccttatcc 
                 
                   
               
               
                   
                 
                   cactaaggacatacttgaagcatagtacctgccctaaatatttgaaggctgtcctaggtattaccaaactc 
                 
                   
               
               
                   
                 
                   aaagaaatgtttacagacacttctgtaCtgtacttgactcgtgctcaacaaaaattctacatgaaaactat 
                 
                   
               
               
                   
                 
                   aggcaatgcagtcaaaggatattacagtaactgtgactcttaacgaaaatcacatattaataggctccttt 
                 
                   
               
               
                   
                 
                   tttggccaattgtattcttgttgatttaatcatattatgttagaaaaaagttgaaccctgactccttaggact 
                 
                   
               
               
                   
                 
                   cgaattcgaactcaaataaatgtcttaaaaaaaggttgcgcacaattattcttgagtgtagtctcgtcattca 
                 
                   
               
               
                   
                 
                   ccaaatctttgtttggt 
                 
                   
               
               
                 Plasmid 
                 TCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAG 
                 85 
               
               
                 pNDV- 
                 CGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATA 
                   
               
               
                 LaSotaL289 
                 ACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAA 
                   
               
               
                 A 
                 AAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCTGACGAGCATCAC 
                   
               
               
                 (Viral 
                 AAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATA 
                   
               
               
                 sequences in 
                 CCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCG 
                   
               
               
                 bold. 
                 CTTACCGGATACCTGTCCGCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATA 
                   
               
               
                 Unique 
                 GCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCT 
                   
               
               
                 restriction 
                 GTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCG 
                   
               
               
                 site Sac II 
                 TCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGG 
                   
               
               
                 (CCGCGG) 
                 TAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGT 
                   
               
               
                 for insertion 
                 GGTGGCCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATCTGCGCTCTGCT 
                   
               
               
                 of foreign 
                 GAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAAC 
                   
               
               
                 genes double 
                 CACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAA 
                   
               
               
                 underlined. 
                 AAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGG 
                   
               
               
                 Mutation 
                 AACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTC 
                   
               
               
                 L289A in the 
                 ACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGA 
                   
               
               
                 F protein. 
                 GTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCG 
                   
               
               
                 CTA = Leu 
                 ATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTAC 
                   
               
               
                 changed to 
                 GATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCC 
                   
               
               
                 GCC = Ala 
                 ACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGA 
                   
               
               
                 (underlined 
                 GCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGC 
                   
               
               
                 and 
                 CGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCC 
                   
               
               
                 italicized).) 
                 ATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCT 
                   
               
               
                   
                 CCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAG 
                   
               
               
                   
                 CGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTT 
                   
               
               
                   
                 ATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAA 
                   
               
               
                   
                 GATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTAT 
                   
               
               
                   
                 GCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACA 
                   
               
               
                   
                 TAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACT 
                   
               
               
                   
                 CTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCC 
                   
               
               
                   
                 AACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAG 
                   
               
               
                   
                 GAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAAT 
                   
               
               
                   
                 ACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCAT 
                   
               
               
                   
                 GAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCG 
                   
               
               
                   
                 CACATTTCCCCGAAAAGTGCCACCTGACGTCTAAGAAACCATTATTATCATGACA 
                   
               
               
                   
                 TTAACCTATAAAAATAGGCGTATCACGAGGCCCTTTCGTCTCGCGCGTTTCGGTG 
                   
               
               
                   
                 ATGACGGTGAAAACCTCTGACACATGCAGCTCCCGGAGACGGTCACAGCTTGTC 
                   
               
               
                   
                 TGTAAGCGGATGCCGGGAGCAGACAAGCCCGTCAGGGCGCGTCAGCGGGTGTT 
                   
               
               
                   
                 GGCGGGTGTCGGGGCTGGCTTAACTATGCGGCATCAGAGCAGATTGTACTGAG 
                   
               
               
                   
                 AGTGCACCATAAAATTGTAAACGTTAATATTTTGTTAAAATTCGCGTTAAATTTTT 
                   
               
               
                   
                 GTTAAATCAGCTCATTTTTTAACCAATAGGCCGAAATCGGCAAAATCCCTTATAA 
                   
               
               
                   
                 ATCAAAAGAATAGCCCGAGATAGGGTTGAGTGTTGTTCCAGTTTGGAACAAGAG 
                   
               
               
                   
                 TCCACTATTAAAGAACGTGGACTCCAACGTCAAAGGGCGAAAAACCGTCTATCA 
                   
               
               
                   
                 GGGCGATGGCCCACTACGTGAACCATCACCCAAATCAAGTTTTTTGGGGTCGAG 
                   
               
               
                   
                 GTGCCGTAAAGCACTAAATCGGAACCCTAAAGGGAGCCCCCGATTTAGAGCTTG 
                   
               
               
                   
                 ACGGGGAAAGCCGGCGAACGTGGCGAGAAAGGAAGGGAAGAAAGCGAAAGG 
                   
               
               
                   
                 AGCGGGCGCTAGGGCGCTGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCA 
                   
               
               
                   
                 CACCCGCCGCGCTTAATGCGCCGCTACAGGGCGCGTACTATGGTTGCTTTGACG 
                   
               
               
                   
                 TATGCGGTGTGAAATACCGCACAGATGCGTAAGGAGAAAATACCGCATCAGGC 
                   
               
               
                   
                 GCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCGGTGCGGGCCT 
                   
               
               
                   
                 CTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTT 
                   
               
               
                   
                 GGGTAACGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGCCA 
                   
               
               
                   
                 AGCTTTAATACGACTCACTATAGGG ACCAAACAGAGAATCCGTGAGTTACGATA   
                   
               
               
                   
                 
                   AAAGGCGAAGGAGCAATTGAAGTCGCACGGGTAGAAGGTGTGAATCTCGAGT 
                 
                   
               
               
                   
                 
                   GCGAGCCCGAAGCACAAACTCGAGAAAGCCTTCTGCCAACATGTCTTCCGTATT 
                 
                   
               
               
                   
                 
                   TGATGAGTACGAACAGCTCCTCGCGGCTCAGACTCGCCCCAATGGAGCTCATG 
                 
                   
               
               
                   
                 
                   GAGGGGGAGAAAAAGGGAGTACCTTAAAAGTAGACGTCCCGGTATTCACTCT 
                 
                   
               
               
                   
                 
                   TAACAGTGATGACCCAGAAGATAGATGGAGCTTTGTGGTATTCTGCCTCCGGA 
                 
                   
               
               
                   
                 
                   TTGCTGTTAGCGAAGATGCCAACAAACCACTCAGGCAAGGTGCTCTCATATCTC 
                 
                   
               
               
                   
                 
                   TTTTATGCTCCCACTCACAGGTAATGAGGAACCATGTTGCCCTTGCAGGGAAAC 
                 
                   
               
               
                   
                 
                   AGAATGAAGCCACATTGGCCGTGCTTGAGATTGATGGCTTTGCCAACGGCACG 
                 
                   
               
               
                   
                 
                   CCCCAGTTCAACAATAGGAGTGGAGTGTCTGAAGAGAGAGCACAGAGATTTG 
                 
                   
               
               
                   
                 
                   CGATGATAGCAGGATCTCTCCCTCGGGCATGCAGCAACGGAACCCCGTTCGTC 
                 
                   
               
               
                   
                 
                   ACAGCCGGGGCCGAAGATGATGCACCAGAAGACATCACCGATACCCTGGAGA 
                 
                   
               
               
                   
                 
                   GGATCCTCTCTATCCAGGCTCAAGTATGGGTCACAGTAGCAAAAGCCATGACT 
                 
                   
               
               
                   
                 
                   GCGTATGAGACTGCAGATGAGTCGGAAACAAGGCGAATCAATAAGTATATGC 
                 
                   
               
               
                   
                 
                   AGCAAGGCAGGGTCCAAAAGAAATACATCCTCTACCCCGTATGCAGGAGCACA 
                 
                   
               
               
                   
                 
                   ATCCAACTCACGATCAGACAGTCTCTTGCAGTCCGCATCTTTTTGGTTAGCGAG 
                 
                   
               
               
                   
                 
                   CTCAAGAGAGGCCGCAACACGGCAGGTGGTACCTCTACTTATTATAACCTGGT 
                 
                   
               
               
                   
                 
                   AGGGGACGTAGACTCATACATCAGGAATACCGGGCTTACTGCATTCTTCTTGAC 
                 
                   
               
               
                   
                 
                   ACTCAAGTACGGAATCAACACCAAGACATCAGCCCTTGCACTTAGTAGCCTCTC 
                 
                   
               
               
                   
                 
                   AGGCGACATCCAGAAGATGAAGCAGCTCATGCGTTTGTATCGGATGAAAGGA 
                 
                   
               
               
                   
                 
                   GATAATGCGCCGTACATGACATTACTTGGTGATAGTGACCAGATGAGCTTTGC 
                 
                   
               
               
                   
                 
                   GCCTGCCGAGTATGCACAACTTTACTCCTTTGCCATGGGTATGGCATCAGTCCT 
                 
                   
               
               
                   
                 
                   AGATAAAGGTACTGGGAAATACCAATTTGCCAGGGACTTTATGAGCACATCAT 
                 
                   
               
               
                   
                 
                   TCTGGAGACTTGGAGTAGAGTACGCTCAGGCTCAGGGAAGTAGCATTAACGA 
                 
                   
               
               
                   
                 
                   GGATATGGCTGCCGAGCTAAAGCTAACCCCAGCAGCAAGGAGGGGCCTGGCA 
                 
                   
               
               
                   
                 
                   GCTGCTGCCCAACGGGTCTCCGAGGAGACCAGCAGCATAGACATGCCTACTCA 
                 
                   
               
               
                   
                 
                   ACAAGTCGGAGTCCTCACTGGGCTTAGCGAGGGGGGGTCCCAAGCTCTACAAG 
                 
                   
               
               
                   
                 
                   GCGGATCGAATAGATCGCAAGGGCAACCAGAAGCCGGGGATGGGGAGACCC 
                 
                   
               
               
                   
                 
                   AATTCCTGGATCTGATGAGAGCGGTAGCAAATAGCATGAGGGAGGCGCCAAA 
                 
                   
               
               
                   
                 
                   CTCTGCACAGGGCACTCCCCAATCGGGGCCTCCCCCAACTCCTGGGCCATCCCA 
                 
                   
               
               
                   
                 
                   AGATAACGACACCGACTGGGGGTATTGATGGACAAAACCCAGCCTGCTTCCAC 
                 
                   
               
               
                   
                 
                   AAAAACATCCCAATGCCCTCACCCGTAGTCGACCCCTCGATTTGCGGCTCTATAT 
                 
                   
               
               
                   
                 
                   GACCACACCCTCAAACAAACATCCCCCTCTTTCCTCCCTCCCCCTGCTGTACAACT 
                 
                   
               
               
                   
                 
                   ACGTACGCCCTAGATACCACAGGCACAATGCGGCTCACTAACAATCAAAACAG 
                 
                   
               
               
                   
                 
                   AGCCGAGGGAATTAGAAAAAAGTACGGGTAGAAGAGGGATATTCAGAGATC 
                 
                   
               
               
                   
                 
                   AGGGCAAGTCTCCCGAGTCTCTGCTCTCTCCTCTACCTGATAGACCAGGACAAA 
                 
                   
               
               
                   
                 
                   CATGGCCACCTTTACAGATGCAGAGATCGACGAGCTATTTGAGACAAGTGGAA 
                 
                   
               
               
                   
                 
                   CTGTCATTGACAACATAATTACAGCCCAGGGTAAACCAGCAGAGACTGTTGGA 
                 
                   
               
               
                   
                 
                   AGGAGTGCAATCCCACAAGGCAAGACCAAGGTGCTGAGCGCAGCATGGGAGA 
                 
                   
               
               
                   
                 
                   AGCATGGGAGCATCCAGCCACCGGCCAGTCAAGACAACCCCGATCGACAGGA 
                 
                   
               
               
                   
                 
                   CAGATCTGACAAACAACCATCCACACCCGAGCAAACGACCCCGCATGACAGCC 
                 
                   
               
               
                   
                 
                   CGCCGGCCACATCCGCCGACCAGCCCCCCACCCAGGCCACAGACGAAGCCGTC 
                 
                   
               
               
                   
                 
                   GACACACAGCTCAGGACCGGAGCAAGCAACTCTCTGCTGTTGATGCTTGACAA 
                 
                   
               
               
                   
                 
                   GCTCAGCAATAAATCGTCCAATGCTAAAAAGGGCCCATGGTCGAGCCCCCAAG 
                 
                   
               
               
                   
                 
                   AGGGGAATCACCAACGTCCGACTCAACAGCAGGGGAGTCAACCCAGTCGCGG 
                 
                   
               
               
                   
                 
                   AAACAGTCAGGAAAGACCGCAGAACCAAGTCAAGGCCGCCCCTGGAAACCAG 
                 
                   
               
               
                   
                 
                   GGCACAGACGTGAACACAGCATATCATGGACAATGGGAGGAGTCACAACTAT 
                 
                   
               
               
                   
                 
                   CAGCTGGTGCAACCCCTCATGCTCTCCGATCAAGGCAGAGCCAAGACAATACC 
                 
                   
               
               
                   
                 
                   CTTGTATCTGCGGATCATGTCCAGCCACCTGTAGACTTTGTGCAAGCGATGATG 
                 
                   
               
               
                   
                 
                   TCTATGATGGAGGCGATATCACAGAGAGTAAGTAAGGTTGACTATCAGCTAGA 
                 
                   
               
               
                   
                 
                   TCTTGTCTTGAAACAGACATCCTCCATCCCTATGATGCGGTCCGAAATCCAACA 
                 
                   
               
               
                   
                 
                   GCTGAAAACATCTGTTGCAGTCATGGAAGCCAACTTGGGAATGATGAAGATTC 
                 
                   
               
               
                   
                 
                   TGGATCCCGGTTGTGCCAACATTTCATCTCTGAGTGATCTACGGGCAGTTGCCC 
                 
                   
               
               
                   
                 
                   GATCTCACCCGGTTTTAGTTTCAGGCCCTGGAGACCCCTCTCCCTATGTGACACA 
                 
                   
               
               
                   
                 
                   AGGAGGCGAAATGGCACTTAATAAACTTTCGCAACCAGTGCCACATCCATCTG 
                 
                   
               
               
                   
                 
                   AATTGATTAAACCCGCCACTGCATGCGGGCCTGATATAGGAGTGGAAAAGGA 
                 
                   
               
               
                   
                 
                   CACTGTCCGTGCATTGATCATGTCACGCCCAATGCACCCGAGTTCTTCAGCCAA 
                 
                   
               
               
                   
                 
                   GCTCCTAAGCAAGTTAGATGCAGCCGGGTCGATCGAGGAAATCAGGAAAATC 
                 
                   
               
               
                   
                 
                   AAGCGCCTTGCTCTAAATGGCTAATTACTACTGCCACACGTAGCGGGTCCCTGT 
                 
                   
               
               
                   
                 
                   CCACTCGGCATCACACGGAATCTGCACCGAGTTCCCCCCCGCGGACCCAAGGTC 
                 
                   
               
               
                   
                 
                   CAACTCTCCAAGCGGCAATCCTCTCTCGCTTCCTCAGCCCCACTGAATGATCGCG 
                 
                   
               
               
                   
                 
                   TAACCGTAATTAATCTAGCTACATTTAAGATTAAGAAAAAATACGGGTAGAAT 
                 
                   
               
               
                   
                 
                   TGGAGTGCCCCAATTGTGCCAAGATGGACTCATCTAGGACAATTGGGCTGTAC 
                 
                   
               
               
                   
                 
                   TTTGATTCTGCCCATTCTTCTAGCAACCTGTTAGCATTTCCGATCGTCCTACAAG 
                 
                   
               
               
                   
                 
                   ACACAGGAGATGGGAAGAAGCAAATCGCCCCGCAATATAGGATCCAGCGCCT 
                 
                   
               
               
                   
                 
                   TGACTTGTGGACTGATAGTAAGGAGGACTCAGTATTCATCACCACCTATGGATT 
                 
                   
               
               
                   
                 
                   CATCTTTCAAGTTGGGAATGAAGAAGCCACCGTCGGCATGATCGATGATAAAC 
                 
                   
               
               
                   
                 
                   CCAAGCGCGAGTTACTTTCCGCTGCGATGCTCTGCCTAGGAAGCGTCCCAAATA 
                 
                   
               
               
                   
                 
                   CCGGAGACCTTATTGAGCTGGCAAGGGCCTGTCTCACTATGATAGTCACATGC 
                 
                   
               
               
                   
                 
                   AAGAAGAGTGCAACTAATACTGAGAGAATGGTTTTCTCAGTAGTGCAGGCACC 
                 
                   
               
               
                   
                 
                   CCAAGTGCTGCAAAGCTGTAGGGTTGTGGCAAACAAATACTCATCAGTGAATG 
                 
                   
               
               
                   
                 
                   CAGTCAAGCACGTGAAAGCGCCAGAGAAGATTCCCGGGAGTGGAACCCTAGA 
                 
                   
               
               
                   
                 
                   ATACAAGGTGAACTTTGTCTCCTTGACTGTGGTACCGAAGAGGGATGTCTACA 
                 
                   
               
               
                   
                 
                   AGATCCCAGCTGCAGTATTGAAGGTTTCTGGCTCGAGTCTGTACAATCTTGCGC 
                 
                   
               
               
                   
                 
                   TCAATGTCACTATTAATGTGGAGGTAGACCCGAGGAGTCCTTTGGTTAAATCTC 
                 
                   
               
               
                   
                 
                   TGTCTAAGTCTGACAGCGGATACTATGCTAACCTCTTCTTGCATATTGGACTTAT 
                 
                   
               
               
                   
                 
                   GACCACTGTAGATAGGAAGGGGAAGAAAGTGACATTTGACAAGCTGGAAAA 
                 
                   
               
               
                   
                 
                   GAAAATAAGGAGCCTTGATCTATCTGTCGGGCTCAGTGATGTGCTCGGGCCTT 
                 
                   
               
               
                   
                 
                   CCGTGTTGGTAAAAGCAAGAGGTGCACGGACTAAGCTTTTGGCACCTTTCTTCT 
                 
                   
               
               
                   
                 
                   CTAGCAGTGGGACAGCCTGCTATCCCATAGCAAATGCTTCTCCTCAGGTGGCCA 
                 
                   
               
               
                   
                 
                   AGATACTCTGGAGTCAAACCGCGTGCCTGCGGAGCGTTAAAATCATTATCCAA 
                 
                   
               
               
                   
                 
                   GCAGGTACCCAACGCGCTGTCGCAGTGACCGCCGACCACGAGGTTACCTCTAC 
                 
                   
               
               
                   
                 
                   TAAGCTGGAGAAGGGGCACACCCTTGCCAAATACAATCCTTTTAAGAAATAAG 
                 
                   
               
               
                   
                 
                   CTGCGTCTCTGAGATTGCGCTCCGCCCACTCACCCAGATCATCATGACACAAAA 
                 
                   
               
               
                   
                 
                   AACTAATCTGTCTTGATTATTTACAGTTAGTTTACCTGTCTATCAAGTTAGAAAA 
                 
                   
               
               
                   
                 
                   AACACGGGTAGAAGATTCTGGATCCCGGTTGGCGCCCTCCAGGTGCAAGATGG 
                 
                   
               
               
                   
                 
                   GCTCCAGACCTTCTACCAAGAACCCAGCACCTATGATGCTGACTATCCGGGTTG 
                 
                   
               
               
                   
                 
                   CGCTGGTACTGAGTTGCATCTGTCCGGCAAACTCCATTGATGGCAGGCCTCTTG 
                 
                   
               
               
                   
                 
                   CAGCTGCAGGAATTGTGGTTACAGGAGACAAAGCCGTCAACATATACACCTCA 
                 
                   
               
               
                   
                 
                   TCCCAGACAGGATCAATCATAGTTAAGCTCCTCCCGAATCTGCCCAAGGATAAG 
                 
                   
               
               
                   
                 
                   GAGGCATGTGCGAAAGCCCCCTTGGATGCATACAACAGGACATTGACCACTTT 
                 
                   
               
               
                   
                 
                   GCTCACCCCCCTTGGTGACTCTATCCGTAGGATACAAGAGTCTGTGACTACATC 
                 
                   
               
               
                   
                 
                   TGGAGGGGGGAGACAGGGGCGCCTTATAGGCGCCATTATTGGCGGTGTGGCT 
                 
                   
               
               
                   
                 
                   CTTGGGGTTGCAACTGCCGCACAAATAACAGCGGCCGCAGCTCTGATACAAGC 
                 
                   
               
               
                   
                 
                   CAAACAAAATGCTGCCAACATCCTCCGACTTAAAGAGAGCATTGCCGCAACCA 
                 
                   
               
               
                   
                 
                   ATGAGGCTGTGCATGAGGTCACTGACGGATTATCGCAACTAGCAGTGGCAGTT 
                 
                   
               
               
                   
                 
                   GGGAAGATGCAGCAGTTTGTTAATGACCAATTTAATAAAACAGCTCAGGAATT 
                 
                   
               
               
                   
                 
                   AGACTGCATCAAAATTGCACAGCAAGTTGGTGTAGAGCTCAACCTGTACCTAA 
                 
                   
               
               
                   
                 
                   CCGAATTGACTACAGTATTCGGACCACAAATCACTTCACCTGCTTTAAACAAGC 
                 
                   
               
               
                   
                 
                   TGACTATTCAGGCACTTTACAATCTAGCTGGTGGAAATATGGATTACTTATTGA 
                 
                   
               
               
                   
                 
                   CTAAGTTAGGTGTAGGGAACAATCAACTCAGCTCATTAATCGGTAGCGGCTTA 
                 
                   
               
               
                   
                 
                   ATCACCGGTAACCCTATTCTATACGACTCACAGACTCAACTCTTGGGTATACAG 
                 
                   
               
               
                   
                 
                   GTAACTGCCCCTTCAGTCGGGAACCTAAATAATATGCGTGCCACCTACTTGGAA 
                 
                   
               
               
                   
                 
                   ACCTTATCCGTAAGCACAACCAGGGGATTTGCCTCGGCACTTGTCCCAAAAGTG 
                 
                   
               
               
                   
                 
                   GTGACACAGGTCGGTTCTGTGATAGAAGAACTTGACACCTCATACTGTATAGA 
                 
                   
               
               
                   
                 
                   AACTGACTTAGATTTATATTGTACAAGAATAGTAACGTTCCCTATGTCCCCTGG 
                 
                   
               
               
                   
                 
                   TATTTATTCCTGCTTGAGCGGCAATACGTCGGCCTGTATGTACTCAAAGACCGA 
                 
                   
               
               
                   
                 
                   AGGCGCACTTACTACACCATACATGACTATCAAAGGTTCAGTCATCGCCAACTG 
                 
                   
               
               
                   
                 
                   CAAGATGACAACATGTAGATGTGTAAACCCCCCGGGTATCATATCGCAAAACT 
                 
                   
               
               
                   
                 
                   ATGGAGAAGCCGTGTCTCTAATAGATAAACAATCATGCAATGTTTTATCCTTAG 
                 
                   
               
               
                   
                 
                   GCGGGATAACTTTAAGGCTCAGTGGGGAATTCGATGTAACTTATCAGAAGAAT 
                 
                   
               
               
                   
                 
                   ATCTCAATACAAGATTCTCAAGTAATAATAACAGGCAATCTTGATATCTCAACT 
                 
                   
               
               
                   
                 
                   GAGCTTGGGAATGTCAACAACTCGATCAGTAATGCTTTGAATAAGTTAGAGGA 
                 
                   
               
               
                   
                 
                   AAGCAACAGAAAACTAGACAAAGTCAATGTCAAACTGACTAGCACATCTGCTC 
                 
                   
               
               
                   
                 
                   TCATTACCTATATCGTTTTGACTATCATATCTCTTGTTTTTGGTATACTTAGCCTG 
                 
                   
               
               
                   
                 
                   ATTCTAGCATGCTACCTAATGTACAAGCAAAAGGCGCAACAAAAGACCTTATT 
                 
                   
               
               
                   
                 
                   ATGGCTTGGGAATAATACTCTAGATCAGATGAGAGCCACTACAAAAATGTGAA 
                 
                   
               
               
                   
                 
                   CACAGATGAGGAACGAAGGTTTCCCTAATAGTAATTTGTGTGAAAGTTCTGGT 
                 
                   
               
               
                   
                 
                   AGTCTGTCAGTTCAGAGAGTTAAGAAAAAACTACCGGTTGTAGATGACCAAAG 
                 
                   
               
               
                   
                 
                   GACGATATACGGGTAGAACGGTAAGAGAGGCCGCCCCTCAATTGCGAGCCAG 
                 
                   
               
               
                   
                 
                   GCTTCACAACCTCCGTTCTACCGCTTCACCGACAACAGTCCTCAATCATGGACCG 
                 
                   
               
               
                   
                 
                   CGCCGTTAGCCAAGTTGCGTTAGAGAATGATGAAAGAGAGGCAAAAAATACA 
                 
                   
               
               
                   
                 
                   TGGCGCTTGATATTCCGGATTGCAATCTTATTCTTAACAGTAGTGACCTTGGCT 
                 
                   
               
               
                   
                 
                   ATATCTGTAGCCTCCCTTTTATATAGCATGGGGGCTAGCACACCTAGCGATCTT 
                 
                   
               
               
                   
                 
                   GTAGGCATACCGACTAGGATTTCCAGGGCAGAAGAAAAGATTACATCTACACT 
                 
                   
               
               
                   
                 
                   TGGTTCCAATCAAGATGTAGTAGATAGGATATATAAGCAAGTGGCCCTTGAGT 
                 
                   
               
               
                   
                 
                   CTCCGTTGGCATTGTTAAATACTGAGACCACAATTATGAACGCAATAACATCTC 
                 
                   
               
               
                   
                 
                   TCTCTTATCAGATTAATGGAGCTGCAAACAACAGTGGGTGGGGGGCACCTATC 
                 
                   
               
               
                   
                 
                   CATGACCCAGATTATATAGGGGGGATAGGCAAAGAACTCATTGTAGATGATG 
                 
                   
               
               
                   
                 
                   CTAGTGATGTCACATCATTCTATCCCTCTGCATTTCAAGAACATCTGAATTTTAT 
                 
                   
               
               
                   
                 
                   CCCGGCGCCTACTACAGGATCAGGTTGCACTCGAATACCCTCATTTGACATGAG 
                 
                   
               
               
                   
                 
                   TGCTACCCATTACTGCTACACCCATAATGTAATATTGTCTGGATGCAGAGATCA 
                 
                   
               
               
                   
                 
                   CTCACATTCATATCAGTATTTAGCACTTGGTGTGCTCCGGACATCTGCAACAGG 
                 
                   
               
               
                   
                 
                   GAGGGTATTCTTTTCTACTCTGCGTTCCATCAACCTGGACGACACCCAAAATCG 
                 
                   
               
               
                   
                 
                   GAAGTCTTGCAGTGTGAGTGCAACTCCCCTGGGTTGTGATATGCTGTGCTCGA 
                 
                   
               
               
                   
                 
                   AAGTCACGGAGACAGAGGAAGAAGATTATAACTCAGCTGTCCCTACGCGGAT 
                 
                   
               
               
                   
                 
                   GGTACATGGGAGGTTAGGGTTCGACGGCCAGTACCACGAAAAGGACCTAGAT 
                 
                   
               
               
                   
                 
                   GTCACAACATTATTCGGGGACTGGGTGGCCAACTACCCAGGAGTAGGGGGTG 
                 
                   
               
               
                   
                 
                   GATCTTTTATTGACAGCCGCGTATGGTTCTCAGTCTACGGAGGGTTAAAACCCA 
                 
                   
               
               
                   
                 
                   ATTCACCCAGTGACACTGTACAGGAAGGGAAATATGTGATATACAAGCGATAC 
                 
                   
               
               
                   
                 
                   AATGACACATGCCCAGATGAGCAAGACTACCAGATTCGAATGGCCAAGTCTTC 
                 
                   
               
               
                   
                 
                   GTATAAGCCTGGACGGTTTGGTGGGAAACGCATACAGCAGGCTATCTTATCTA 
                 
                   
               
               
                   
                 
                   TCAAGGTGTCAACATCCTTAGGCGAAGACCCGGTACTGACTGTACCGCCCAAC 
                 
                   
               
               
                   
                 
                   ACAGTCACACTCATGGGGGCCGAAGGCAGAATTCTCACAGTAGGGACATCTCA 
                 
                   
               
               
                   
                 
                   TTTCTTGTATCAACGAGGGTCATCATACTTCTCTCCCGCGTTATTATATCCTATG 
                 
                   
               
               
                   
                 
                   ACAGTCAGCAACAAAACAGCCACTCTTCATAGTCCTTATACATTCAATGCCTTC 
                 
                   
               
               
                   
                 
                   ACTCGGCCAGGTAGTATCCCTTGCCAGGCTTCAGCAAGATGCCCCAACTCGTGT 
                 
                   
               
               
                   
                 
                   GTTACTGGAGTCTATACAGATCCATATCCCCTAATCTTCTATAGAAACCACACCT 
                 
                   
               
               
                   
                 
                   TGCGAGGGGTATTCGGGACAATGCTTGATGGTGTACAAGCAAGACTTAACCCT 
                 
                   
               
               
                   
                 
                   GCGTCTGCAGTATTCGATAGCACATCCCGCAGTCGCATTACTCGAGTGAGTTCA 
                 
                   
               
               
                   
                 
                   AGCAGTACCAAAGCAGCATACACAACATCAACTTGTTTTAAAGTGGTCAAGAC 
                 
                   
               
               
                   
                 
                   TAATAAGACCTATTGTCTCAGCATTGCTGAAATATCTAATACTCTCTTCGGAGA 
                 
                   
               
               
                   
                 
                   ATTCAGAATCGTCCCGTTACTAGTTGAGATCCTCAAAGATGACGGGGTTAGAG 
                 
                   
               
               
                   
                 
                   AAGCCAGGTCTGGCTAGTTGAGTCAATTATAAAGGAGTTGGAAAGATGGCATT 
                 
                   
               
               
                   
                 
                   GTATCACCTATCTTCTGCGACATCAAGAATCAAACCGAATGCCGGCGCGTGCTC 
                 
                   
               
               
                   
                 
                   GAATTCCATGTTGCCAGTTGACCACAATCAGCCAGTGCTCATGCGATCAGATTA 
                 
                   
               
               
                   
                 
                   AGCCTTGTCAATAGTCTCTTGATTAAGAAAAAATGTAAGTGGCAATGAGATAC 
                 
                   
               
               
                   
                 
                   AAGGCAAAACAGCTCATGGTTAACAATACGGGTAGGACATGGCGAGCTCCGG 
                 
                   
               
               
                   
                 
                   TCCTGAAAGGGCAGAGCATCAGATTATCCTACCAGAGTCACACCTGTCTTCACC 
                 
                   
               
               
                   
                 
                   ATTGGTCAAGCACAAACTACTCTATTACTGGAAATTAACTGGGCTACCGCTTCC 
                 
                   
               
               
                   
                 
                   TGATGAATGTGACTTCGACCACCTCATTCTCAGCCGACAATGGAAAAAAATACT 
                 
                   
               
               
                   
                 
                   TGAATCGGCCTCTCCTGATACTGAGAGAATGATAAAACTCGGAAGGGCAGTAC 
                 
                   
               
               
                   
                 
                   ACCAAACTCTTAACCACAATTCCAGAATAACCGGAGTGCTCCACCCCAGGTGTT 
                 
                   
               
               
                   
                 
                   TAGAAGAACTGGCTAATATTGAGGTCCCAGATTCAACCAACAAATTTCGGAAG 
                 
                   
               
               
                   
                 
                   ATTGAGAAGAAGATCCAAATTCACAACACGAGATATGGAGAACTGTTCACAA 
                 
                   
               
               
                   
                 
                   GGCTGTGTACGCATATAGAGAAGAAACTGCTGGGGTCATCTTGGTCTAACAAT 
                 
                   
               
               
                   
                 
                   GTCCCCCGGTCAGAGGAGTTCAGCAGCATTCGTACGGATCCGGCATTCTGGTTT 
                 
                   
               
               
                   
                 
                   CACTCAAAATGGTCCACAGCCAAGTTTGCATGGCTCCATATAAAACAGATCCA 
                 
                   
               
               
                   
                 
                   GAGGCATCTGATGGTGGCAGCTAGGACAAGGTCTGCGGCCAACAAATTGGTG 
                 
                   
               
               
                   
                 
                   ATGCTAACCCATAAGGTAGGCCAAGTCTTTGTCACTCCTGAACTTGTCGTTGTG 
                 
                   
               
               
                   
                 
                   ACGCATACGAATGAGAACAAGTTCACATGTCTTACCCAGGAACTTGTATTGAT 
                 
                   
               
               
                   
                 
                   GTATGCAGATATGATGGAGGGCAGAGATATGGTCAACATAATATCAACCACG 
                 
                   
               
               
                   
                 
                   GCGGTGCATCTCAGAAGCTTATCAGAGAAAATTGATGACATTTTGCGGTTAAT 
                 
                   
               
               
                   
                 
                   AGACGCTCTGGCAAAAGACTTGGGTAATCAAGTCTACGATGTTGTATCACTAA 
                 
                   
               
               
                   
                 
                   TGGAGGGATTTGCATACGGAGCTGTCCAGCTACTCGAGCCGTCAGGTACATTT 
                 
                   
               
               
                   
                 
                   GCAGGAGATTTCTTCGCATTCAACCTGCAGGAGCTTAAAGACATTCTAATTGGC 
                 
                   
               
               
                   
                 
                   CTCCTCCCCAATGATATAGCAGAATCCGTGACTCATGCAATCGCTACTGTATTCT 
                 
                   
               
               
                   
                 
                   CTGGTTTAGAACAGAATCAAGCAGCTGAGATGTTGTGTCTGTTGCGTCTGTGG 
                 
                   
               
               
                   
                 
                   GGTCACCCACTGCTTGAGTCCCGTATTGCAGCAAAGGCAGTCAGGAGCCAAAT 
                 
                   
               
               
                   
                 
                   GTGCGCACCGAAAATGGTAGACTTTGATATGATCCTTCAGGTACTGTCTTTCTT 
                 
                   
               
               
                   
                 
                   CAAGGGAACAATCATCAACGGGTACAGAAAGAAGAATGCAGGTGTGTGGCCG 
                 
                   
               
               
                   
                 
                   CGAGTCAAAGTGGATACAATATATGGGAAGGTCATTGGGCAACTACATGCAG 
                 
                   
               
               
                   
                 
                   ATTCAGCAGAGATTTCACACGATATCATGTTGAGAGAGTATAAGAGTTTATCT 
                 
                   
               
               
                   
                 
                   GCACTTGAATTTGAGCCATGTATAGAATATGACCCTGTCACCAACCTGAGCATG 
                 
                   
               
               
                   
                 
                   TTCCTAAAAGACAAGGCAATCGCACACCCCAACGATAATTGGCTTGCCTCGTTT 
                 
                   
               
               
                   
                 
                   AGGCGGAACCTTCTCTCCGAAGACCAGAAGAAACATGTAAAAGAAGCAACTTC 
                 
                   
               
               
                   
                 
                   GACTAATCGCCTCTTGATAGAGTTTTTAGAGTCAAATGATTTTGATCCATATAA 
                 
                   
               
               
                   
                 
                   AGAGATGGAATATCTGACGACCCTTGAGTACCTTAGAGATGACAATGTGGCAG 
                 
                   
               
               
                   
                 
                   TATCATACTCGCTCAAGGAGAAGGAAGTGAAAGTTAATGGACGGATCTTCGCT 
                 
                   
               
               
                   
                 
                   AAGCTGACAAAGAAGTTAAGGAACTGTCAGGTGATGGCGGAAGGGATCCTAG 
                 
                   
               
               
                   
                 
                   CCGATCAGATTGCACCTTTCTTTCAGGGAAATGGAGTCATTCAGGATAGCATAT 
                 
                   
               
               
                   
                 
                   CCTTGACCAAGAGTATGCTAGCGATGAGTCAACTGTCTTTTAACAGCAATAAG 
                 
                   
               
               
                   
                 
                   AAACGTATCACTGACTGTAAAGAAAGAGTATCTTCAAACCGCAATCATGATCC 
                 
                   
               
               
                   
                 
                   GAAAAGCAAGAACCGTCGGAGAGTTGCAACCTTCATAACAACTGACCTGCAAA 
                 
                   
               
               
                   
                 
                   AGTACTGTCTTAATTGGAGATATCAGACAATCAAATTGTTCGCTCATGCCATCA 
                 
                   
               
               
                   
                 
                   ATCAGTTGATGGGCCTACCTCACTTCTTCGAATGGATTCACCTAAGACTGATGG 
                 
                   
               
               
                   
                 
                   ACACTACGATGTTCGTAGGAGACCCTTTCAATCCTCCAAGTGACCCTACTGACT 
                 
                   
               
               
                   
                 
                   GTGACCTCTCAAGAGTCCCTAATGATGACATATATATTGTCAGTGCCAGAGGG 
                 
                   
               
               
                   
                 
                   GGTATCGAAGGATTATGCCAGAAGCTATGGACAATGATCTCAATTGCTGCAAT 
                 
                   
               
               
                   
                 
                   CCAACTTGCTGCAGCTAGATCGCATTGTCGTGTTGCCTGTATGGTACAGGGTGA 
                 
                   
               
               
                   
                 
                   TAATCAAGTAATAGCAGTAACGAGAGAGGTAAGATCAGACGACTCTCCGGAG 
                 
                   
               
               
                   
                 
                   ATGGTGTTGACACAGTTGCATCAAGCCAGTGATAATTTCTTCAAGGAATTAATT 
                 
                   
               
               
                   
                 
                   CATGTCAATCATTTGATTGGCCATAATTTGAAGGATCGTGAAACCATCAGGTCA 
                 
                   
               
               
                   
                 
                   GACACATTCTTCATATACAGCAAACGAATCTTCAAAGATGGAGCAATCCTCAGT 
                 
                   
               
               
                   
                 
                   CAAGTCCTCAAAAATTCATCTAAATTAGTGCTAGTGTCAGGTGATCTCAGTGAA 
                 
                   
               
               
                   
                 
                   AACACCGTAATGTCCTGTGCCAACATTGCCTCTACTGTAGCACGGCTATGCGAG 
                 
                   
               
               
                   
                 
                   AACGGGCTTCCCAAAGACTTCTGTTACTATTTAAACTATATAATGAGTTGTGTG 
                 
                   
               
               
                   
                 
                   CAGACATACTTTGACTCTGAGTTCTCCATCACCAACAATTCGCACCCCGATCTTA 
                 
                   
               
               
                   
                 
                   ATCAGTCGTGGATTGAGGACATCTCTTTTGTGCACTCATATGTTCTGACTCCTGC 
                 
                   
               
               
                   
                 
                   CCAATTAGGGGGACTGAGTAACCTTCAATACTCAAGGCTCTACACTAGAAATA 
                 
                   
               
               
                   
                 
                   TCGGTGACCCGGGGACTACTGCTTTTGCAGAGATCAAGCGACTAGAAGCAGTG 
                 
                   
               
               
                   
                 
                   GGATTACTGAGTCCTAACATTATGACTAATATCTTAACTAGGCCGCCTGGGAAT 
                 
                   
               
               
                   
                 
                   GGAGATTGGGCCAGTCTGTGCAACGACCCATACTCTTTCAATTTTGAGACTGTT 
                 
                   
               
               
                   
                 
                   GCAAGCCCAAATATTGTTCTTAAGAAACATACGCAAAGAGTCCTATTTGAAACT 
                 
                   
               
               
                   
                 
                   TGTTCAAATCCCTTATTGTCTGGAGTGCACACAGAGGATAATGAGGCAGAAGA 
                 
                   
               
               
                   
                 
                   GAAGGCATTGGCTGAATTCTTGCTTAATCAAGAGGTGATTCATCCCCGCGTTGC 
                 
                   
               
               
                   
                 
                   GCATGCCATCATGGAGGCAAGCTCTGTAGGTAGGAGAAAGCAAATTCAAGGG 
                 
                   
               
               
                   
                 
                   CTTGTTGACACAACAAACACCGTAATTAAGATTGCGCTTACTAGGAGGCCATTA 
                 
                   
               
               
                   
                 
                   GGCATCAAGAGGCTGATGCGGATAGTCAATTATTCTAGCATGCATGCAATGCT 
                 
                   
               
               
                   
                 
                   GTTTAGAGACGATGTTTTTTCCTCCAGTAGATCCAACCACCCCTTAGTCTCTTCT 
                 
                   
               
               
                   
                 
                   AATATGTGTTCTCTGACACTGGCAGACTATGCACGGAATAGAAGCTGGTCACC 
                 
                   
               
               
                   
                 
                   TTTGACGGGAGGCAGGAAAATACTGGGTGTATCTAATCCTGATACGATAGAAC 
                 
                   
               
               
                   
                 
                   TCGTAGAGGGTGAGATTCTTAGTGTAAGCGGAGGGTGTACAAGATGTGACAG 
                 
                   
               
               
                   
                 
                   CGGAGATGAACAATTTACTTGGTTCCATCTTCCAAGCAATATAGAATTGACCGA 
                 
                   
               
               
                   
                 
                   TGACACCAGCAAGAATCCTCCGATGAGGGTACCATATCTCGGGTCAAAGACAC 
                 
                   
               
               
                   
                 
                   AGGAGAGGAGAGCTGCCTCACTTGCAAAAATAGCTCATATGTCGCCACATGTA 
                 
                   
               
               
                   
                 
                   AAGGCTGCCCTAAGGGCATCATCCGTGTTGATCTGGGCTTATGGGGATAATGA 
                 
                   
               
               
                   
                 
                   AGTAAATTGGACTGCTGCTCTTACGATTGCAAAATCTCGGTGTAATGTAAACTT 
                 
                   
               
               
                   
                 
                   AGAGTATCTTCGGTTACTGTCCCCTTTACCCACGGCTGGGAATCTTCAACATAG 
                 
                   
               
               
                   
                 
                   ACTAGATGATGGTATAACTCAGATGACATTCACCCCTGCATCTCTCTACAGGGT 
                 
                   
               
               
                   
                 
                   GTCACCTTACATTCACATATCCAATGATTCTCAAAGGCTGTTCACTGAAGAAGG 
                 
                   
               
               
                   
                 
                   AGTCAAAGAGGGGAATGTGGTTTACCAACAGATCATGCTCTTGGGTTTATCTCT 
                 
                   
               
               
                   
                 
                   AATCGAATCGATCTTTCCAATGACAACAACCAGGACATATGATGAGATCACAC 
                 
                   
               
               
                   
                 
                   TGCACCTACATAGTAAATTTAGTTGCTGTATCAGAGAAGCACCTGTTGCGGTTC 
                 
                   
               
               
                   
                 
                   CTTTCGAGCTACTTGGGGTGGTACCGGAACTGAGGACAGTGACCTCAAATAAG 
                 
                   
               
               
                   
                 
                   TTTATGTATGATCCTAGCCCTGTATCGGAGGGAGACTTTGCGAGACTTGACTTA 
                 
                   
               
               
                   
                 
                   GCTATCTTCAAGAGTTATGAGCTTAATCTGGAGTCATATCCCACGATAGAGCTA 
                 
                   
               
               
                   
                 
                   ATGAACATTCTTTCAATATCCAGCGGGAAGTTGATTGGCCAGTCTGTGGTTTCT 
                 
                   
               
               
                   
                 
                   TATGATGAAGATACCTCCATAAAGAATGACGCCATAATAGTGTATGACAATAC 
                 
                   
               
               
                   
                 
                   CCGAAATTGGATCAGTGAAGCTCAGAATTCAGATGTGGTCCGCCTATTTGAAT 
                 
                   
               
               
                   
                 
                   ATGCAGCACTTGAAGTGCTCCTCGACTGTTCTTACCAACTCTATTACCTGAGAGT 
                 
                   
               
               
                   
                 
                   AAGAGGCCTGGACAATATTGTCTTATATATGGGTGATTTATACAAGAATATGC 
                 
                   
               
               
                   
                 
                   CAGGAATTCTACTTTCCAACATTGCAGCTACAATATCTCATCCCGTCATTCATTC 
                 
                   
               
               
                   
                 
                   AAGGTTACATGCAGTGGGCCTGGTCAACCATGACGGATCACACCAACTTGCAG 
                 
                   
               
               
                   
                 
                   ATACGGATTTTATCGAAATGTCTGCAAAACTATTAGTATCTTGCACCCGACGTG 
                 
                   
               
               
                   
                 
                   TGATCTCCGGCTTATATTCAGGAAATAAGTATGATCTGCTGTTCCCATCTGTCTT 
                 
                   
               
               
                   
                 
                   AGATGATAACCTGAATGAGAAGATGCTTCAGCTGATATCCCGGTTATGCTGTCT 
                 
                   
               
               
                   
                 
                   GTACACGGTACTCTTTGCTACAACAAGAGAAATCCCGAAAATAAGAGGCTTAA 
                 
                   
               
               
                   
                 
                   CTGCAGAAGAGAAATGTTCAATACTCACTGAGTATTTACTGTCGGATGCTGTG 
                 
                   
               
               
                   
                 
                   AAACCATTACTTAGCCCCGATCAAGTGAGCTCTATCATGTCTCCTAACATAATTA 
                 
                   
               
               
                   
                 
                   CATTCCCAGCTAATCTGTACTACATGTCTCGGAAGAGCCTCAATTTGATCAGGG 
                 
                   
               
               
                   
                 
                   AAAGGGAGGACAGGGATACTATCCTGGCGTTGTTGTTCCCCCAAGAGCCATTA 
                 
                   
               
               
                   
                 
                   TTAGAGTTCCCTTCTGTGCAAGATATTGGTGCTCGAGTGAAAGATCCATTCACC 
                 
                   
               
               
                   
                 
                   CGACAACCTGCGGCATTTTTGCAAGAGTTAGATTTGAGTGCTCCAGCAAGGTA 
                 
                   
               
               
                   
                 
                   TGACGCATTCACACTTAGTCAGATTCATCCTGAACTCACATCTCCAAATCCGGA 
                 
                   
               
               
                   
                 
                   GGAAGACTACTTAGTACGATACTTGTTCAGAGGGATAGGGACTGCATCTTCCT 
                 
                   
               
               
                   
                 
                   CTTGGTATAAGGCATCTCATCTCCTTTCTGTACCCGAGGTAAGATGTGCAAGAC 
                 
                   
               
               
                   
                 
                   ACGGGAACTCCTTATACTTAGCTGAAGGGAGCGGAGCCATCATGAGTCTTCTC 
                 
                   
               
               
                   
                 
                   GAACTGCATGTACCACATGAAACTATCTATTACAATACGCTCTTTTCAAATGAG 
                 
                   
               
               
                   
                 
                   ATGAACCCCCCGCAACGACATTTCGGGCCGACCCCAACTCAGTTTTTGAATTCG 
                 
                   
               
               
                   
                 
                   GTTGTTTATAGGAATCTACAGGCGGAGGTAACATGCAAAGATGGATTTGTCCA 
                 
                   
               
               
                   
                 
                   AGAGTTCCGTCCATTATGGAGAGAAAATACAGAGGAAAGCGACCTGACCTCA 
                 
                   
               
               
                   
                 
                   GATAAAGTAGTGGGGTATATTACATCTGCAGTGCCCTACAGATCTGTATCATTG 
                 
                   
               
               
                   
                 
                   CTGCATTGTGACATTGAAATTCCTCCAGGGTCCAATCAAAGCTTACTAGATCAA 
                 
                   
               
               
                   
                 
                   CTAGCTATCAATTTATCTCTGATTGCCATGCATTCTGTAAGGGAGGGCGGGGTA 
                 
                   
               
               
                   
                 
                   GTAATCATCAAAGTGTTGTATGCAATGGGATACTACTTTCATCTACTCATGAAC 
                 
                   
               
               
                   
                 
                   TTGTTTGCTCCGTGTTCCACAAAAGGATATATTCTCTCTAATGGTTATGCATGTC 
                 
                   
               
               
                   
                 
                   GAGGAGATATGGAGTGTTACCTGGTATTTGTCATGGGTTACCTGGGCGGGCCT 
                 
                   
               
               
                   
                 
                   ACATTTGTACATGAGGTGGTGAGGATGGCGAAAACTCTGGTGCAGCGGCACG 
                 
                   
               
               
                   
                 
                   GTACGCTTTTGTCTAAATCAGATGAGATCACACTGACCAGGTTATTCACCTCAC 
                 
                   
               
               
                   
                 
                   AGCGGCAGCGTGTGACAGACATCCTATCCAGTCCTTTACCAAGATTAATAAAG 
                 
                   
               
               
                   
                 
                   TACTTGAGGAAGAATATTGACACTGCGCTGATTGAAGCCGGGGGACAGCCCGT 
                 
                   
               
               
                   
                 
                   CCGTCCATTCTGTGCGGAGAGTCTGGTGAGCACGCTAGCGAACATAACTCAGA 
                 
                   
               
               
                   
                 
                   TAACCCAGATCATCGCTAGTCACATTGACACAGTTATCCGGTCTGTGATATATA 
                 
                   
               
               
                   
                 
                   TGGAAGCTGAGGGTGATCTCGCTGACACAGTATTTCTATTTACCCCTTACAATC 
                 
                   
               
               
                   
                 
                   TCTCTACTGACGGGAAAAAGAGGACATCACTTAAACAGTGCACGAGACAGATC 
                 
                   
               
               
                   
                 
                   CTAGAGGTTACAATACTAGGTCTTAGAGTCGAAAATCTCAATAAAATAGGCGA 
                 
                   
               
               
                   
                 
                   TATAATCAGCCTAGTGCTTAAAGGCATGATCTCCATGGAGGACCTTATCCCACT 
                 
                   
               
               
                   
                 
                   AAGGACATACTTGAAGCATAGTACCTGCCCTAAATATTTGAAGGCTGTCCTAG 
                 
                   
               
               
                   
                 
                   GTATTACCAAACTCAAAGAAATGTTTACAGACACTTCTGTACTGTACTTGACTC 
                 
                   
               
               
                   
                 
                   GTGCTCAACAAAAATTCTACATGAAAACTATAGGCAATGCAGTCAAAGGATAT 
                 
                   
               
               
                   
                 
                   TACAGTAACTGTGACTCTTAACGAAAATCACATATTAATAGGCTCCTTTTTTGG 
                 
                   
               
               
                   
                 
                   CCAATTGTATTCTTGTTGATTTAATCATATTATGTTAGAAAAAAGTTGAACCCTG 
                 
                   
               
               
                   
                 
                   ACTCCTTAGGACTCGAATTCGAACTCAAATAAATGTCTTAAAAAAAGGTTGCGC 
                 
                   
               
               
                   
                   ACAATTATTCTTGAGTGTAGTCTCGTCATTCACCAAATCTTTGTTTGGT GCGCGC 
                   
               
               
                   
                 GGCCGGCATGGTCCCAGCCTCCTCGCTGGCGCCGGCTGGGCAACATTCCGAGG 
                   
               
               
                   
                 GGACCGTCCCCTCGGTAATGGCGAATGGGACGTCGACTGCTAACAAAGCCCGA 
                   
               
               
                   
                 AAGGAAGCTGAGTTGGCTGCTGCCACCGCTGAGCAATAACTAGCATAACCCCTT 
                   
               
               
                   
                 GGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTGCTGAAAGGAGGAACTATATGC 
                   
               
               
                   
                 GCGCAGATCTGTCATGATGATCATTGCAATTGGATCCATATATAGGGCCCGGGT 
                   
               
               
                   
                 TATAATTACCTCAGGTCGACGTCCCATGGCCATTCGAATTCGTAATCATGGTCAT 
                   
               
               
                   
                 AGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGC 
                   
               
               
                   
                 CGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATT 
                   
               
               
                   
                 AATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTG 
                   
               
               
                   
                 CATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGC 
                   
               
               
                 Full length 
                 ACGAAAAAGAAGAATAAAAGGCAGAAGCCTTTTAAAAGGAACCCTGGGCTGTC 
                 86 
               
               
                 genome of 
                 GTAGGTGTGGGAAGGTTGTATTCCGAGTGCGCCTCCGAGGCATCTACTCTACA 
                   
               
               
                 APMV4 
                 CCTATCACAATGGCTGGTGTCTTCTCCCAGTATGAGAGGTTTGTGGACAATCAA 
                   
               
               
                 from RNA 
                 TCCCAAGTGTCAAGGAAGGATCATCGGTCCTTAGCAGGAGGATGCCTTAAAGT 
                   
               
               
                 sequencing 
                 TAACATCCCTATGCTTGTCACTGCATCTGAAGACCCCACCACTCGTTGGCAACT 
                   
               
               
                 and 
                 AGCATGCTTATCTCTAAGGCTCCTGATCTCCAACTCATCAACCAGTGCTATCCG 
                   
               
               
                 confirmation 
                 TCAGGGGGCAATACTGACTCTCATGTCATTACCATCACAAAACATGAGAGCAAC 
                   
               
               
                 of the 5’ and 
                 AGCAGCTATTGCTGGTTCCACAAATGCAGCTGTTATCAACACCATGGAAGTCTT 
                   
               
               
                 3’ ends by 
                 AAGTGTCAACGACTGGACCCCATCCTTCGACCCTAGGAGCGGTCTTTCTGAGG 
                   
               
               
                 RACE 
                 AAGATGCTCAAGTTTTCAGAGACATGGCAAGAGATCTGCCCCCTCAGTTCACCT 
                   
               
               
                   
                 CTGGATCACCCTTCACATCAGCATTGGCGGAGGGGTTCACTCCTGAAGATACT 
                   
               
               
                   
                 CATGACCTGATGGAGGCCTTGACCAGTGTGCTGATACAGATCTGGATCCTGGT 
                   
               
               
                   
                 GGCTAAGGCCATGACCAACATTGACGGCTCTGGGGAGGCCAATGAAAGACGT 
                   
               
               
                   
                 CTTGCAAAGTACATCCAAAAAGGACAGCTTAATCGTCAGTTTGCAATTGGTAAT 
                   
               
               
                   
                 CCTGCCCGTCTGATAATCCAACAGACAATCAAAAGCTCCTTAACTGTCCGTAGG 
                   
               
               
                   
                 TTCTTGGTCTCTGAGCTTCGTGCGTCACGAGGTGCAGTAAAAGAAGGATCCCC 
                   
               
               
                   
                 TTACTATGCAGCTGTTGGGGATATCCACGCTTACATCTTTAATGCGGGATTGAC 
                   
               
               
                   
                 ACCATTCTTGACCACCTTAAGATACGGGATAGGCACCAAGTACGCCGCTGTTG 
                   
               
               
                   
                 CACTCAGTGTGTTCGCTGCAGATATTGCAAAGTTGAAGAGCCTACTTACCCTGT 
                   
               
               
                   
                 ACCAGGACAAGGGTGTAGAAGCTGGATACATGGCACTCCTTGAGGATCCAGAC 
                   
               
               
                   
                 TCCATGCACTTTGCACCTGGAAACTTCCCACACATGTACTCCTATGCAATGGGG 
                   
               
               
                   
                 GTAGCTTCTTACCATGATCCTAGCATGCGCCAATACCAATACGCCAGGAGGTTC 
                   
               
               
                   
                 CTCAGCCGTCCTTTCTACTTACTAGGAAGGGACATGGCCGCCAAGAACACAGG 
                   
               
               
                   
                 CACGCTGGATGAGCAACTGGCGAAGGAACTGCAAGTATCAGAGAGAGATCGC 
                   
               
               
                   
                 GCCGCATTATCCGCTGCGATTCAATCAGCGATGGAGGGGGGAGAGTCCGACG 
                   
               
               
                   
                 ACTTCCCACTGTCGGGATCCATGCCGGCTCTCTCTGAGAATGCGCAACCAGTT 
                   
               
               
                   
                 ACCCCCAGACCTCAACAGTCCCAGCTCTCTCCCCCCCAATCATCAAACATGCC 
                   
               
               
                   
                 CCAATCAGCACCCAGGACCCCAGACTATCAACCCGACTTTGAACTGTAGGCTT 
                   
               
               
                   
                 CATCACCGCACCAACAACAGCCCAAGAAGACCACCCCTCCCCCCACACATCTC 
                   
               
               
                   
                 ACCCAGCCACCCATAAAGACTCAGTCCCACGCCCCAGCATCTCCTTCATTTAAT 
                   
               
               
                   
                 TAAAAACCGACCAACAGGGTGGGGAAGGAGAGTCATTGGCTACTGCCAATTGT 
                   
               
               
                   
                 GTGCAGCAATGGATTTTACTGACATTGATCTGTCAACTCATTGATCGAATCAT 
                   
               
               
                   
                 CATCGGCAATCATAGACTCCATACAGCATGGAGGGCTGCAACCAGCGGGCAC 
                   
               
               
                   
                 CGTCGGCCTATCGCAGATCCCAAAAGGGATAACCAGCGCATTAACCAAGGCCT 
                   
               
               
                   
                 GGGAGGCTGAGGCGGCAACTGCCGGTAATGGGGACACCCAACACAAATCTGA 
                   
               
               
                   
                 CAGTCCGGAGGATCATCAGGCCAACGACACAGATTCCCCTGAAGACACAGGTA 
                   
               
               
                   
                 CTGACCAGACCACCCAGGAGGCCAACATCGTTGAGACACCCCACCCCGAGGT 
                   
               
               
                   
                 GCTGTCAGCAGCCAAAGCCAGACTCAAGAGGCCCAAAGCAGGGAGGGACACC 
                   
               
               
                   
                 CGCGACAACTCCCCTGCGCAACCCGATCATCTTTTAAGGGGGGCCTCCTGAG 
                   
               
               
                   
                 CCCACAACCAGCAGCATCATGGGTGCAAAATCCACCCAGTCATGGAGGTCCCG 
                   
               
               
                   
                 GCACCGCCGATCCCCGCCCATCACAAACTCAGGATCATTCCCCCACCGGAGA 
                   
               
               
                   
                 GAAATGGCGATTGTCACCGACAAAGCAACCGGAGACATTGAACTGGTGGAGTG 
                   
               
               
                   
                 GTGCAACCCGGGGTGCACAGCAGTCCGAATTGAACCCACCAGACTCGACTGT 
                   
               
               
                   
                 GTATGCGGACACTGCCCCACCATCTGTAGCCTCTGCATGTATGACGACTGATC 
                   
               
               
                   
                 AGGTACAACTACTAATGAAGGAGGTTGCTGACATAAAATCACTCCTTCAGGCGT 
                   
               
               
                   
                 TAGTGAGGAACCTCGCTGTCTTGCCCCAATTGAGGAATGAGGTTGCAGCAATC 
                   
               
               
                   
                 AGAACATCACAGGCCATGATAGAGGGGACACTCAATTCGATCAAGATTCTTGAC 
                   
               
               
                   
                 CCTGGGAATTATCAGGAATCATCACTAAACAGTTGGTTCAAACCTCGCCAAGAT 
                   
               
               
                   
                 CACACTGTTGTTGTGTCTGGACCAGGGAATCCATTGGCCATGCCAACCCCAGT 
                   
               
               
                   
                 CCAAGACAACACCATATTCCTGGACGAGCTAGCCAGACCTCATCCTAGTGTGG 
                   
               
               
                   
                 TCAATCCATCCCCGCCCATCACCAACACCAATGTTGACCTTGGCCCACAGAAG 
                   
               
               
                   
                 CAGGCTGCAATAGCCTATATCTCCGCTAAATGCAAGGATCCGGGGAAACGAGA 
                   
               
               
                   
                 TCAGCTATCAAGGCTCATTGAGCGAGCAACCACCCCAAGTGAGATCAACAAAG 
                   
               
               
                   
                 TTAAAAGACAAGCCCTTGGGCTCTAGATCACTCGATCACCCCTCATGGTGATCA 
                   
               
               
                   
                 CAACAATAATCAGAACCCTTCCGAACCACATGACCAACCCAGCCCACCGCCCA 
                   
               
               
                   
                 CACCGTCCATCGACATCCCTTGCCAAACATCCTGCCGTAGCTGATTTATTCAAA 
                   
               
               
                   
                 AGAGCTCATTTGATATGACCTGGTAATCATAAAATAGGGTGGGGAAGGTGCTTT 
                   
               
               
                   
                 GCCTGTAAGGGGGCTCCCTCATCTTCAGACACGTGCCCGCCATCTCACCAACA 
                   
               
               
                   
                 GTGCAATGGCAGACATGGACACGGTGTATATCAATCTGATGGCAGATGACCCA 
                   
               
               
                   
                 ACCCACCAAAAAGAACTGCTGTCCTTTCCTCTCATCCCTGTGACCGGTCCTGAC 
                   
               
               
                   
                 GGGAAGAAGGAACTCCAACACCAGATCCGGACCCAATCCTTGCTCGCCTCAGA 
                   
               
               
                   
                 CAAACAAACTGAACGGTTCATCTTCCTCAACACTTACGGATTCATCTATGACAC 
                   
               
               
                   
                 CACACCGGACAAGACAACTTTTTCCACCCCAGAGCATATTAATCAGCCTAAGAG 
                   
               
               
                   
                 GACGACGGTGAGTGCCGCGATGATGACCATTGGCCTGGTTCCCGCCAATATAC 
                   
               
               
                   
                 CCCTGAACGAACTAACGGCTACTGTGTTCAGCCTTAAAGTAAGAGTGAGGAAA 
                   
               
               
                   
                 AGTGCGAGGTATCGGGAAGTGGTCTGGTATCAATGCAATCCAGTACCGGCCCT 
                   
               
               
                   
                 GCTTGCAGCCACCAGGTTTGGTCGCCAAGGAGGTCTCGAGTCGAGCACTGGA 
                   
               
               
                   
                 GTCAGTGTAAAGGCTCCCGAGAAGATAGATTGTGAGAAGGATTATACCTACTAC 
                   
               
               
                   
                 CCTTATTTCTTATCTGTGTGCTACATCGCCACCTCCAACCTGTTCAAGGTACCG 
                   
               
               
                   
                 AGGATGGTTGCTAATGCAACCAACAGTCAATTATACCACCTTACCATGCAGGTC 
                   
               
               
                   
                 ACATTTGCCTTTCCAAAAAACATCCCTCCAGCCAACCAGAAACTCCTGACACAG 
                   
               
               
                   
                 GTGGATGAGGGATTCGAGGGCACTGTGGATTGCCATTTTGGGAACATGCTGAA 
                   
               
               
                   
                 AAAGGATCGGAAAGGGAACATGAGGACACTGTCCCAGGCGGCAGATAAGGTC 
                   
               
               
                   
                 AGACGAATGAATATTCTTGTTGGTATCTTTGACTTGCATGGGCCAACGCTCTTC 
                   
               
               
                   
                 CTGGAGTATACCGGGAAACTGACAAAGGCTCTGCTAGGGTTCATGTCCACCAG 
                   
               
               
                   
                 CCGAACAGCAATCATCCCCATATCTCAGCTCAATCCCATGCTGAGTCAACTCAT 
                   
               
               
                   
                 GTGGAGCAGTGATGCCCAGATAGTAAAGTTAAGGGTTGTCATAACTACATCCAA 
                   
               
               
                   
                 ACGCGGCCCGTGCGGGGGTGAGCAGGAGTATGTGCTGGATCCCAAATTCACA 
                   
               
               
                   
                 GTTAAGAAAGAAAAGGCTCGACTCAACCCTTTCAAGAAGGCAGCCTAATGATTT 
                   
               
               
                   
                 AATCCGCAAGATCCCAGAAATCAGACCACTCTATACTATCCACTGATCACTGGA 
                   
               
               
                   
                 AATGTAATTGTACAGTTGATGAATCTGTGAAGAATCAATTAAAAAACCGGATCCT 
                   
               
               
                   
                 TATTAGGGTGGGGAAGTAGTTGATTGGGTGTCTAAACAAAAGCATTTCTTCACA 
                   
               
               
                   
                 CCTCCCCGCCACGAAACAACCACAATGAGGCTATCAAACACAATCTTGACCTTG 
                   
               
               
                   
                 ATTCTCATCATACTTACCGGCTATTTGATAGGTGTCCACTCCACCGATGTGAAT 
                   
               
               
                   
                 GAGAAACCAAAGTCCGAAGGGATTAGGGGTGATCTTACACCAGGTGCGGGTAT 
                   
               
               
                   
                 TTTCGTAACTCAAGTCCGACAGCTCCAGATCTACCAACAGTCTGGGTACCATGA 
                   
               
               
                   
                 TCTTGTCATCAGATTGTTACCTCTTCTACCAACAGAGCTTAATGATTGTCAAAGG 
                   
               
               
                   
                 GAAGTTGTCACAGAGTACAATAACACTGTATCACAGCTGTTGCAGCCTATCAAA 
                   
               
               
                   
                 ACCAACCTGGATACTTTGTTGGCAGATGGTAGCACAAGGGATGTTGATATACAG 
                   
               
               
                   
                 CCGCGATTCATTGGGGCAATAATAGCCACAGGTGCCCTGGCTGTAGCAACGGT 
                   
               
               
                   
                 AGCTGAGGTAACTGCAGCTCAAGCACTATCTCAGTCAAAAACGAATGCTCAAAA 
                   
               
               
                   
                 TATTCTCAAGTTGAGAGATAGTATTCAGGCCACCAACCAAGCAGTTTTTGAAATT 
                   
               
               
                   
                 TCACAGGGACTCGAAGCAACTGCAACCGTGCTATCAAAACTGCAAACTGAGCT 
                   
               
               
                   
                 CAATGAGAATATCATCCCAAGTCTGAACAACTTGTCCTGTGCTGCCATGGGGAA 
                   
               
               
                   
                 TCGCCTTGGTGTATCACTCTCACTCTATTTGACCTTAATGACCACTCTATTTGGG 
                   
               
               
                   
                 GACCAGATCACAAACCCAGTGCTGACGCCAATCTCTTACAGCACCCTATCGGC 
                   
               
               
                   
                 AATGGCGGGTGGTCACATTGGTCCAGTGATGAGTAAGATATTAGCCGGATCTG 
                   
               
               
                   
                 TCACAAGTCAGTTGGGGGCAGAACAACTGATTGCTAGTGGCTTAATACAGTCA 
                   
               
               
                   
                 CAGGTAGTAGGTTATGATTCCCAGTATCAGCTGTTGGTTATCAGGGTCAACCTT 
                   
               
               
                   
                 GTACGGATTCAGGAAGTCCAGAATACTAGGGTTGTATCACTAAGAACACTAGCA 
                   
               
               
                   
                 GTCAATAGGGATGGTGGACTTTACAGAGCCCAGGTGCCACCCGAGGTAGTTGA 
                   
               
               
                   
                 GCGATCTGGCATTGCAGAGCGGTTTTATGCAGATGATTGTGTTCTAACTACAAC 
                   
               
               
                   
                 TGATTACATCTGCTCATCGATCCGATCTTCTCGGCTTAATCCAGAGTTAGTCAA 
                   
               
               
                   
                 GTGTCTCAGTGGGGCACTTGATTCATGCACATTTGAGAGGGAAAGTGCATTACT 
                   
               
               
                   
                 GTCAACTCCCTTCTTTGTATACAACAAGGCAGTCGTCGCAAATTGTAAAGCAGC 
                   
               
               
                   
                 GACATGTAGATGTAATAAACCGCCATCTATCATTGCCCAATACTCTGCATCAGC 
                   
               
               
                   
                 TCTAGTAACCATCACCACCGACACTTGTGCTGACCTTGAAATTGAGGGTTATCG 
                   
               
               
                   
                 TTTCAACATACAGACTGAATCCAACTCATGGGTTGCACCAAACTTCACGGTCTC 
                   
               
               
                   
                 AACCTCACAAATAGTATCGGTTGATCCAATAGACATATCCTCTGACATTGCCAA 
                   
               
               
                   
                 AATTAACAATTCTATCGAGGCTGCGCGAGAGCAGCTGGAACTGAGCAACCAGA 
                   
               
               
                   
                 TCCTTTCCCGAATCAACCCACGGATTGTGAACGACGAATCACTAATAGCTATTA 
                   
               
               
                   
                 TCGTGACAATTGTTGTGCTTAGTCTCCTTGTAATTGGTCTTATTATTGTTCTCGG 
                   
               
               
                   
                 TGTGATGTACAAGAATCTTAAGAAAGTCCAACGAGCTCAAGCTGCTATGATGAT 
                   
               
               
                   
                 GCAGCAAATGAGCTCATCACAGCCTGTGACCACCAAATTGGGGACACCCTTCT 
                   
               
               
                   
                 AGGTGAATAATCATATCAATCCATTCAATAATGAGCGGGACATACCAATCACCA 
                   
               
               
                   
                 ACGACTGTGTCACAAGGCCGGTTAGGAATGCACCGGATCTCTCTCCTTCCTTTT 
                   
               
               
                   
                 TAATTAAAAACGGTTGAACTGAGGGTGAGGGGGGGGGTGTGCATGGTAGGGT 
                   
               
               
                   
                 GGGGAAGGTAGCCAATTCCTGCCCATTGGGCCGACCGTACCAAGAGAAGTCA 
                   
               
               
                   
                 ACAGAAGTATAGATGCAGGGCGACATGGAGGGTAGCCGTGATAACCTCACAGT 
                   
               
               
                   
                 AGATGATGAATTAAAGACAACATGGAGGTTAGCTTATAGAGTTGTATCCCTCCT 
                   
               
               
                   
                 ATTGATGGTGAGTGCCTTGATAATCTCTATAGTAATCCTGACGAGAGATAACAG 
                   
               
               
                   
                 CCAAAGCATAATCACGGCGATCAACCAGTCGTATGACGCAGACTCAAAGTGGC 
                   
               
               
                   
                 AAACAGGGATAGAAGGGAAAATCACCTCAATCATGACTGATACGCTCGATACCA 
                   
               
               
                   
                 GGAATGCAGCTCTTCTCCACATTCCACTCCAGCTCAATACACTTGAGGCAAACC 
                   
               
               
                   
                 TGTTGTCCGCCCTCGGAGGTAACACGGGAATTGGCCCCGGAGATCTAGAGCA 
                   
               
               
                   
                 CTGTCGTTATCCGGTTCATGACTCCGCTTACCTGCATGGAGTCAATCGATTACT 
                   
               
               
                   
                 CATCAATCAAACAGCTGACTACACAGCAGAAGGCCCCCTGGATCATGTGAACT 
                   
               
               
                   
                 TCATTCCGGCACCAGTTACGACTACTGGATGCACAAGGATCCCATCCTTTTCTG 
                   
               
               
                   
                 TATCATCATCCATTTGGTGCTATACACACAATGTGATTGAAACAGGTTGCAATGA 
                   
               
               
                   
                 CCACTCAGGTAGTAATCAATATATCAGTATGGGGGTGATTAAGAGGGCTGGCA 
                   
               
               
                   
                 ACGGCTTACCTTACTTCTCAACAGTCGTGAGTAAGTATCTGACCGATGGGTTGA 
                   
               
               
                   
                 ATAGAAAAAGCTGTTCCGTAGCTGCCGGATCCGGGCATTGTTACCTCCTTTGTA 
                   
               
               
                   
                 GCCTAGTGTCAGAGCCCGAACCTGATGACTATGTGTCACCAGATCCCACACCG 
                   
               
               
                   
                 ATGAGGTTAGGGGTGCTAACAAGGGATGGGTCTTACACTGAACAGGTGGTACC 
                   
               
               
                   
                 CGAAAGAATATTTAAGAACATATGGAGCGCAAACTACCCTGGGGTAGGGTCAG 
                   
               
               
                   
                 GTGCTATAGTAGGAAATAAGGTGTTATTCCCATTTTACGGCGGAGTGAAGAATG 
                   
               
               
                   
                 GATCAACCCCTGAGGTGATGAATAGGGGAAGATATTACTACATCCAGGATCCA 
                   
               
               
                   
                 AATGACTATTGCCCTGACCCGCTGCAAGATCAGATCTTAAGGGCAGAACAATC 
                   
               
               
                   
                 GTATTATCCTACTCGATTTGGTAGGAGGATGGTAATGCAGGGAGTCCTAACATG 
                   
               
               
                   
                 TCCAGTATCCAACAATTCAACAATAGCCAGCCAATGCCAATCTTACTATTTCAAC 
                   
               
               
                   
                 AACTCATTAGGATTCATCGGGGCGGAATCTAGGATCTATTACCTCAATGGTAAC 
                   
               
               
                   
                 ATTTACCTTTATCAAAGAAGCTCGAGCTGGTGGCCTCACCCCCAAATTTACCTA 
                   
               
               
                   
                 CTTGATTCCAGGATTGCAAGTCCGGGTACGCAGAACATTGACTCAGGCGTTAA 
                   
               
               
                   
                 CCTCAAGATGTTAAATGTTACTGTCATTACACGACCATCATCTGGCTTTTGTAAT 
                   
               
               
                   
                 AGTCAGTCAAGATGCCCTAATGACTGCTTATTCGGGGTTTATTCAGATGTCTGG 
                   
               
               
                   
                 CCTCTTAGCCTTACCTCAGACAGCATATTTGCATTTACAATGTACTTACAAGGGA 
                   
               
               
                   
                 AGACGACACGTATTGACCCAGCTTGGGCGCTATTCTCCAATCATGTAATTGGG 
                   
               
               
                   
                 CATGAGGCTCGTTTGTTCAACAAGGAGGTTAGTGCTGCTTATTCTACCACCACT 
                   
               
               
                   
                 TGTTTTTCGGACACCATCCAAAACCAGGTGTATTGTCTGAGTATACTTGAAGTC 
                   
               
               
                   
                 AGAAGTGAGCTCTTGGGGGCATTCAAGATAGTGCCATTCCTCTATCGTGTCTTA 
                   
               
               
                   
                 TAGGCACCTGCTTGGTCAAGAACCCTGAGCAGCCATAAAATTAACACTTGATCT 
                   
               
               
                   
                 TCCTTAAAAACACCTATCTAAATTACTGTCTGAGATCCCTGATTAGTTACCCTTT 
                   
               
               
                   
                 CAATCAATCAATTAATTTTTAATTAAAAACGGAAAAATGGGCCTAGTTCCAAGGA 
                   
               
               
                   
                 AAGGATGGGACCCATTAGGGTGGGGAAGGATTACTTTGTTCCTTGACTCGCAC 
                   
               
               
                   
                 CCACGTACACCCAATCCCATTCCTGTCAAGAAGGAACCCTTCCCAAACTCACCT 
                   
               
               
                   
                 TGCAATGTCCAATCAGGCAGCTGAGATTATACTACCCACCTTCCATCTGGAATC 
                   
               
               
                   
                 ACCCTTGATCGAGAATAAGTGCTTCTACTACATGCAATTACTTGGTCTCGTGTTA 
                   
               
               
                   
                 CCACATGATCACTGGAGATGGAGGGCATTCGTCAA1111ACAGTGGATCAAGC 
                   
               
               
                   
                 ACACCTTAAAAATCGTAATCCCCGCTTAATGGCCCACATCGATCACACTAAGGA 
                   
               
               
                   
                 TAGACTAAGGGCTCATGGTGTCTTGGGTTTCCACCAGACTCAGACAAGTGAGA 
                   
               
               
                   
                 GCCGTTTCCGTGTCTTGCTCCATCCTGAAACTTTACCTTGGCTATCAGCAATGG 
                   
               
               
                   
                 GAGGATGCATCAACCAGGTTCCCAAGGCATGGCGGAACACTCTGAAATCTATC 
                   
               
               
                   
                 GAGCACAGTGTGAAGCAGGAGGCGACTCAACTGAAGTTACTCATGGAAAAAAC 
                   
               
               
                   
                 CTCACTAAAGCTAACAGGAGTATCTTACTTATTCTCCAATTGCAATCCCGGGAA 
                   
               
               
                   
                 AACTGCAGCGGGAACTATGCCCGTACTAAGTGAGATGGCATCAGAACTCTTGT 
                   
               
               
                   
                 CAAATCCCATCTCCCAATTCCAATCAACATGGGGGTGTGCTGCTTCAGGGTGG 
                   
               
               
                   
                 CACCATGTAGTCAGCATCATGAGGCTCCAACAGTATCAAAGAAGGACAGGTAA 
                   
               
               
                   
                 GGAAGAGAAAGCAATCACTGAAGTTCAGTATGGCTCGGACACCTGTCTCATTAA 
                   
               
               
                   
                 TGCAGACTACACCGTCGTTTTTTCCTCACAGGACCGTGTCATAGCAGTCTTGC 
                   
               
               
                   
                 CTTTCGATGTTGTCCTCATGATGCAAGACCTGCTTGAATCCCGACGGAATGTCT 
                   
               
               
                   
                 TGTTCTGTGCCCGCTTTATGTATCCCAGAAGCCAACTACATGAGAGGATAAGTA 
                   
               
               
                   
                 CAATACTGGCCCTTGGAGACCAACTCGGGAGAAAAGCACCCCAAGTCCTGTAT 
                   
               
               
                   
                 GATTTCGTAGCTACCCTCGAATCATTTGCATACGCTGCTGTCCAACTTCATGAC 
                   
               
               
                   
                 AACAACCCTATCTACGGTGGGGCTTTCTTTGAGTTCAATATCCAAGAACTGGAA 
                   
               
               
                   
                 GCTA1111GTCCCCTGCACTTAATAAGGATCAAGTCAACTTCTACATAAGTCAAG 
                   
               
               
                   
                 TTGTCTCAGCATACAGTAACCTTCCCCCATCTGAATCAGCAGAATTGCTATGCT 
                   
               
               
                   
                 TACTACGCCTGTGGGGTCATCCCTTGCTAAACAGTCTTGATGCAGCAAAGAAA 
                   
               
               
                   
                 GTCAGAGAATCTATGTGTGCTGGGAAGGTTCTTGATTATAATGCTATTCGACTA 
                   
               
               
                   
                 GIIIIGICIIIIIATCATACGTTATTAATCAATGGGTATCGGAAGAAACATAAGG 
                   
               
               
                   
                 GTCGCTGGCCAAATGTGAATCAACATTCACTACTCAACCCGATAGTGAAGCAG 
                   
               
               
                   
                 CTTTACTTTGATCAGGAGGAGATCCCACACTCTGTTGCCCTTGAGCACTATTTA 
                   
               
               
                   
                 GATATCTCGATGATAGAATTTGAGAAGACTTTTGAAGTGGAACTATCTGATAGT 
                   
               
               
                   
                 CTAAGCATCTTTCTGAAGGATAAGTCGATAGCTTTGGATAAACAAGAATGGCAC 
                   
               
               
                   
                 AGTGGTTTTGTCTCAGAAGTGACTCCAAAGCACCTACGAATGTCTCGTCATGAT 
                   
               
               
                   
                 CGCAAGTCTACCAATAGGCTATTGTTAGCCTTTATTAACTCCCCTGAATTCGAT 
                   
               
               
                   
                 GTTAAGGAAGAGCTTAAATATTTGACTACAGGTGAGTATGCCACTGACCCAAAT 
                   
               
               
                   
                 TTCAATGTCTCTTACTCACTGAAAGAGAAGGAAGTTAAGAAAGAAGGGCGCATT 
                   
               
               
                   
                 TTCGCAAAGATGTCACAGAAAATGAGAGCATGCCAGGTTATTTGTGAAGAGTTA 
                   
               
               
                   
                 CTAGCACATCATGTGGCTCCTTTGTTTAAAGAGAATGGTGTTACACAATCGGAG 
                   
               
               
                   
                 CTATCCCTGACAAAGAATTTGTTGGCTATTAGCCAACTGAGTTACAACTCGATG 
                   
               
               
                   
                 GCCGCTAAGGTGCGATTGCTGAGGCCAGGGGACAAGTTCACCGCTGCACACT 
                   
               
               
                   
                 ATATGACCACAGACCTAAAAAAGTACTGCCTTAACTGGCGGCACCAGTCAGTCA 
                   
               
               
                   
                 AATTGTTCGCCAGAAGCCTGGATCGACTATTTGGGTTAGACCATGCTTTTTCTT 
                   
               
               
                   
                 GGATACACGTCCGTCTCACCAATAGCACTATGTACGTTGCTGACCCATTCAATC 
                   
               
               
                   
                 CACCAGACTCAGATGCATGCACAAATTTAGACGACAATAAGAACACTGGGATTT 
                   
               
               
                   
                 TTATTATAAGTGCTCGAGGTGGTATAGAAGGCCTTCAACAGAAACTATGGACTG 
                   
               
               
                   
                 GCATATCAATTGCAATCGCCCAGGCGGCAGCAGCCCTCGAGGGCTTACGAATT 
                   
               
               
                   
                 GCTGCCACTTTGCAGGGGGATAACCAGGTTTTAGCGATTACGAAAGAATTCAT 
                   
               
               
                   
                 GACCCCAGTCTCGGAGGATGTAATCCACGAGCAGCTATCTGAAGCGATGTCGC 
                   
               
               
                   
                 GATACAAGAGGACTTTCACATACCTTAATTATTTAATGGGGCACCAATTGAAGG 
                   
               
               
                   
                 ATAAAGAAACCATCCAATCCAGTGACTTCTTCGTTTACTCCAAAAGGATCTTCTT 
                   
               
               
                   
                 CAATGGGTCAATCCTAAGTCAATGCCTCAAGAACTTCAGTAAACTCACTACCAA 
                   
               
               
                   
                 TGCCACTACCCTTGCTGAGAACACTGTAGCCGGCTGCAGTGACATCTCCTCAT 
                   
               
               
                   
                 GCATAGCCCGTTGTGTGGAAAACGGGTTGCCTAAGGATGCTGCATATGTTCAG 
                   
               
               
                   
                 AATATAATCATGACTCGGCTTCAACTGTTGCTAGATCACTACTATTCTATGCATG 
                   
               
               
                   
                 GTGGCATAAACTCAGAGTTAGAGCAGCCAACTCTAAGTATCCCTGTCCGAAAC 
                   
               
               
                   
                 GCAACCTATTTACCATCTCAATTAGGCGGTTACAATCATTTGAATATGACCCGA 
                   
               
               
                   
                 CTATTCTGTCGCAATATCGGTGACCCGCTTACTAGTTCTTGGGCAGAGTCAAAA 
                   
               
               
                   
                 AGACTAATGGATGTTGGCCTTCTCAGTCGTAAGTTCTTAGAGGGGATATTATGG 
                   
               
               
                   
                 AGACCCCGGGAAGTGGGACATTTTCAACACTCATGCTTGATCCGTTCGCACT 
                   
               
               
                   
                 TAACATTGATTACTTAAGGCCACCAGAGACAATAATCCGAAAACACACCCAAAA 
                   
               
               
                   
                 AGTCTTGTTGCAGGATTGTCCTAATCCTCTATTAGCAGGTGTAGTTGACCCGAA 
                   
               
               
                   
                 CTACAACCAGGAATTAGAATTATTAGCTCAGTTCCTGCTTGATCGGGAAACCGT 
                   
               
               
                   
                 TATTCCCAGGGCTGCCCATGCCATCTTTGAACTGTCTGTCTTGGGAAGGAAAAA 
                   
               
               
                   
                 ACATATACAAGGATTGGTTGATACTACAAAAACAATTATTCAGTGCTCATTAGAA 
                   
               
               
                   
                 AGACAGCCACTGTCCTGGAGGAAAGTTGAGAACATTGTAACCTACAATGCGCA 
                   
               
               
                   
                 GTATTTCCTCGGGGCCACCCAGCAGGTTGACACCAATATCTCAGAAAGGCAGT 
                   
               
               
                   
                 GGGTGATGCCAGGTAATTTCAAGAAGCTTGTATCTCTTGACGATTGCTCAGTCA 
                   
               
               
                   
                 CGTTGTCCACTGTGTCACGGCGCATTTCTTGGGCCAATCTACTTAACTGGAGG 
                   
               
               
                   
                 GCTATAGATGGTTTGGAAACTCCAGATGTGATAGAGAGTATTGATGGCCGCCTT 
                   
               
               
                   
                 GTGCAATCATCCAATCAATGCGGCCTATGTAATCAAGGATTGGGCTCCTACTCC 
                   
               
               
                   
                 TGGTTCTTCTTGCCCTCCGGGTGTGTGTTCGACCGTCCACAAGATTCTCGAGT 
                   
               
               
                   
                 GGTTCCAAAGATGCCATACGTGGGATCCAAAACGGATGAGAGACAGACTGCGT 
                   
               
               
                   
                 CAGTGCAGGCTATACAGGGATCCACATGTCACCTTAGAGCAGCATTGAGACTT 
                   
               
               
                   
                 GTATCACTCTACCTTTGGGCCTATGGAGATTCTGACATATCATGGCTAGAAGCC 
                   
               
               
                   
                 GCGACATTGGCTCAAACACGGTGCAATATTTCTCTTGATGACCTGCGGATCCTG 
                   
               
               
                   
                 AGCCCTCTTCCTTCCTCGGCAAATTTACACCACAGATTGAATGACGGGGTAACA 
                   
               
               
                   
                 CAAGTGAAATTCATGCCCGCCACATCGAGCCGGGTGTCAAAGTTCGTCCAAAT 
                   
               
               
                   
                 TTGCAATGACAACCAGAATCTTATCCGTGATGATGGGAGTGTTGATTCCAATAT 
                   
               
               
                   
                 GATTTATCAGCAGGTTATGATATTAGGGCTTGGAGAGATTGAATGTTTGTTAGC 
                   
               
               
                   
                 TGACCCAATCGATACAAACCCAGAACAACTGATTCTTCACCTACACTCTGATAA 
                   
               
               
                   
                 TTCTTGCTGTCTCCGGGAGATGCCAACGACCGGTTTTGTACCTGCTTTAGGATT 
                   
               
               
                   
                 GACCCCATGCTTAACTGTCCCAAAGCACAATCCGTATATTTATGATGATAGCCC 
                   
               
               
                   
                 AATACCCGGTGATTTGGATCAGAGGCTCATTCAAACCAAATTCTTTATGGGTTC 
                   
               
               
                   
                 TGACAATCTAGATAATCTTGATATCTACCAGCAGCGAGCTTTACTGAGTCGGTG 
                   
               
               
                   
                 TGTGGCTTATGACATTATCCAATCAGTATTCGCTTGCGATGCACCAGTATCTCA 
                   
               
               
                   
                 GAAGAATGATGCAATCCTTCACACTGACTACCATGAAAATTGGATCTCAGAGTT 
                   
               
               
                   
                 CCGATGGGGTGACCCTCGCATAATCCAAGTAACAGCAGGTTACGAGTTAATTC 
                   
               
               
                   
                 TGTTCCTTGCATACCAGCTTTATTATCTCAGAGTGAGGGGTGACCGTGCAATCC 
                   
               
               
                   
                 TGTGTTATATTGATAGGATACTCAACAGGATGGTATCTTCCAATCTAGGCAGTC 
                   
               
               
                   
                 TCATCCAGACGCTCTCTCATCCGGAGATTAGGAGGAGATTTTCATTGAGTGATC 
                   
               
               
                   
                 AAGGGTTCCTTGTCGAAAGGGAGCTAGAGCCAGGTAAGCCACTGGTAAAACAA 
                   
               
               
                   
                 GCGGTTATGTTCCTAAGGGACTCAGTCCGCTGCGCTTTAGCAACTATCAAGGC 
                   
               
               
                   
                 AGGAATTGAGCCTGAGATCTCCCGAGGTGGCTGTACCCAGGATGAGCTGAGCT 
                   
               
               
                   
                 TTACCCTTAAGCACTTACTATGTCGGCGTCTCTGTATAATTGCTCTCATGCATTC 
                   
               
               
                   
                 GGAAGCAAAGAACTTGGTCAAAGTTAGAAACCTTCCAGTAGAGGAAAAAACCG 
                   
               
               
                   
                 CCTTACTATACCAGATGTTGATCACTGAGGCCAATGCCAGGAGATCAGGGTCT 
                   
               
               
                   
                 GCTAGTATCATCATAAGCTTAGTTTCAGCACCCCAGTGGGACATTCATACACCA 
                   
               
               
                   
                 GCGTTGTATTTTGTATCAAAGAAAATGCTGGGGATGCTCAAAAGGTCAACCACA 
                   
               
               
                   
                 CCCTTGGATATAAGTGACCTTTCTGAGAGCCAGAACCTCACACCAACAGAATTG 
                   
               
               
                   
                 AATGATGTTCCTGGTCACATGGCAGAGGAATTTCCCTGTTTGTTTAGCAGTTAT 
                   
               
               
                   
                 AACGCTACATATGAAGACACAATTACTTACAATCCAATGACTGAAAAACTCGCA 
                   
               
               
                   
                 GTGCACTTGGACAATGGTTCCACCCCTTCCAGAGCGCTTGGTCGTCACTACAT 
                   
               
               
                   
                 CCTGCGACCCCTTGGGCTTTACTCGTCTGCATGGTACCGGTCTGCAGCACTAT 
                   
               
               
                   
                 TAGCGTCAGGGGCCCTCAGTGGGTTGCCTGAGGGGTCAAGCCTGTACTTGGG 
                   
               
               
                   
                 AGAGGGGTATGGGACCACCATGACTCTACTTGAGCCCGTTGTCAAGTCCTCAA 
                   
               
               
                   
                 CTGTTTACTACCATACATTGTTTGACCCAACCCGGAATCCTTCACAGCGGAACT 
                   
               
               
                   
                 ACAAACCAGAACCGCGGGTATTCACTGATTCCATTTGGTACAAGGATGATTTCA 
                   
               
               
                   
                 CACGACCACCTGGTGGCATTGTAAATCTATGGGGTGAAGACGTACGTCAGAGT 
                   
               
               
                   
                 GATATTACACAGAAAGACACGGTTAATTTCATATTATCTCGGGTCCCGCCAAAA 
                   
               
               
                   
                 TCACTCAAATTGATACACGTTGATATTGAGTTCTCCCCAGACTCTGATGTACGG 
                   
               
               
                   
                 ACGCTACTATCTGGCTATTCCCATTGTGCACTATTGGCCTACTGGCTACTGCAA 
                   
               
               
                   
                 CCTGGAGGGCGATTTGCGGTTAGAGTTTTCTTAAGTGACCATATCATAGTCAAC 
                   
               
               
                   
                 TTGGTCACTGCCATTCTGTCCGCTTTTGACTCTAATCTGGTGTGCATTGCGTCA 
                   
               
               
                   
                 GGATTGACACACAAGGATGATGGGGCAGGTTATATTTGTGCAAAGAAGCTTGC 
                   
               
               
                   
                 AAATGTTGAGGCTTCAAGAATTGAGTATTACTTGAGGATGGTCCACGGCTGTGT 
                   
               
               
                   
                 TGACTCATTAAAAATTCCTCATCAATTAGGAATCATTAAATGGGCTGAGGGTGA 
                   
               
               
                   
                 AGTGTCCCGACTTACCAAAAAGGCGGATGATGAAATAAACTGGCGGTTAGGTG 
                   
               
               
                   
                 ATCCAGTTACCAGATCATTTGATCCGGTTTCTGAGCTAATAATTGCGCGAACAG 
                   
               
               
                   
                 GGGGATCAGTATTAATGGAATACGGGACTTTTACTAACCTCAGGTGTGCGAACT 
                   
               
               
                   
                 TGGGCAGATACATATAAACTTTTGGCTTCAATTGTAGAGACCACCTTAATGGAAAT 
                   
               
               
                   
                 AAGGGTTGAGCAAGATCAGTTGGAAGATGATTCGAGGAGACAAATCCAGGTAG 
                   
               
               
                   
                 TCCCTGCTTTTAATACAAGATCCGGGGAAGGATCCGTACATTGATTGAGTGTG 
                   
               
               
                   
                 CTCAGCTGCAGGTCATAGATGTTATCTGTGTGAACATAGATCACCTCTTTCCCA 
                   
               
               
                   
                 AACACCGACATGCTCTTGTCACACAACTTACTTACCAGTCAGTGTGCCTTGGGG 
                   
               
               
                   
                 ACTTGATTGAAGGCCCCCAAATTAAGACATATCTAAGGGCCAGGAAGTGGATC 
                   
               
               
                   
                 CAACGTAGGGGACTCAATGAGACAATTAACCATATCATCACTGGACAAGTGTCG 
                   
               
               
                   
                 CGGAATAAGGCAAGGGATTTTTTCAAGAGGCGCCTGAAGTTGGTTGGCTTTTC 
                   
               
               
                   
                 GCTCTGTGGCGGTTGGGGCTACCTCTCACTTTAGCTGCTTAGATTGTTGATTAT 
                   
               
               
                   
                 TATGAATAATCGGAGTCGAAATCGTAAATAGAAAGACATAAAATTGCAAATAAG 
                   
               
               
                   
                 CAATGATCGTATTAATATTTAATAAAAAATATGTCTTTTATTTCTT 
                   
               
               
                 Additional 
                 ccgcggTTAGAAAAAATACGGGTAGAACCGCCACC ATGCATCTGCTGTGTTTCCT   
                 87 
               
               
                 transcription 
                 
                   GTCGCTCGCCTGCTCACTGCTGGCGGCGGCACTTATCCCGTCCCCACGGGAG 
                 
                   
               
               
                 unit 
                 
                   GCTCCTGCCACCGTGGCCGCCTTCGAATCTGGGCTGGGCTTCAGCGAAGCCG 
                 
                   
               
               
                 encoding 
                 
                   AGCCCGATGGCGGAGAGGTCAAGGCATTCGAAGGAAAGGACCTCGAAGAAC 
                 
                   
               
               
                 mVEGF-C. 
                 
                   AGCTGAGATCCGTGTCCTCCGTGGACGAACTCATGTCCGTCCTGTACCCCGA 
                 
                   
               
               
                 (size = 1290 
                 
                   TTACTGGAAGATGTACAAATGCCAGCTCCGGAAGGGCGGTTGGCAGCAGCC 
                 
                   
               
               
                 nt, rule of 
                 
                   CACTCTGAACACTCGCACGGGAGATTCCGTGAAGTTTGCCGCCGCCCACTAC 
                 
                   
               
               
                 6). 
                 
                   AATACTGAGATTCTCAAGTCCATCGACAACGAATGGAGGAAAACCCAGTGTA 
                 
                   
               
               
                 Open reading 
                 
                   TGCCGCGCGAAGTCTGCATTGACGTGGGAAAGGAGTTCGGCGCTGCCACCA 
                 
                   
               
               
                 frame in 
                 
                   ACACCTTCTTTAAGCCTCCCTGCGTGTCGGTGTATCGCTGCGGGGGATGCTG 
                 
                   
               
               
                 bold. 
                 
                   CAACAGCGAAGGCCTTCAGTGCATGAACACCAGCACCGGATACCTCAGCAA 
                 
                   
               
               
                   
                 
                   GACTCTCTTCGAAATCACTGTGCCGCTGTCACAAGGCCCGAAGCCTGTGACC 
                 
                   
               
               
                   
                 
                   ATTTCCTTCGCCAACCACACCTCCTGTCGGTGCATGAGCAAGCTGGATGTGTA 
                 
                   
               
               
                   
                 
                   CAGACAGGTGCACTCCATCATCCGGAGATCGTTGCCTGCCACCCTGCCGCAG 
                 
                   
               
               
                   
                 
                   TGCCAAGCGGCTAACAAGACCTGTCCCACCAACTACGTGTGGAACAACTATA 
                 
                   
               
               
                   
                 
                   TGTGTCGGTGCCTGGCACAGCAGGACTTTATCTTCTACTCCAACGTGGAGGA 
                 
                   
               
               
                   
                 
                   CGACTCGACTAACGGTTTCCACGACGTGTGCGGACCCAACAAGGAGCTGGAT 
                 
                   
               
               
                   
                 
                   GAGGATACTTGTCAGTGCGTGTGCAAGGGTGGCCTGCGCCCGTCCTCCTGCG 
                 
                   
               
               
                   
                 
                   GACCACATAAGGAACTGGACAGGGACTCGTGCCAATGCGTCTGCAAGAACA 
                 
                   
               
               
                   
                 
                   AGCTGTTCCCTAACTCCTGCGGGGCGAACCGCGAATTCGACGAGAACACCTG 
                 
                   
               
               
                   
                 
                   TCAGTGTGTGTGCAAGCGGACTTGCCCGAGGAATCAGCCTCTTAACCCCGGA 
                 
                   
               
               
                   
                 
                   AAATGCGCCTGCGAATGCACAGAGAACACCCAGAAGTGCTTCTTGAAAGGG 
                 
                   
               
               
                   
                 
                   AAGAAGTTCCACCACCAAACCTGTTCATGCTACCGGCGCCCATGTGCCAACC 
                 
                   
               
               
                   
                 
                   GGCTGAAGCACTGCGACCCGGGATTGAGCTTCAGCGAGGAGGTCTGCAGAT 
                 
                   
               
               
                   
                 
                   GCGTGCCGTCATACTGGAAGCGACCTCATCTGAATTAGCccgcgg 
                 
                   
               
               
                 Rescue 
                 TCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAG 
                 88 
               
               
                 plasmid 
                 CGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATA 
                   
               
               
                 pNDV- 
                 ACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAA 
                   
               
               
                 mVEGF-C 
                 AAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATA 
                   
               
               
                 with the 
                 AAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATA 
                   
               
               
                 mVEGF-C 
                 CCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCG 
                   
               
               
                 transcription 
                 CTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATA 
                   
               
               
                 unit inserted 
                 GCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCT 
                   
               
               
                 at the unique 
                 GTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCG 
                   
               
               
                 Sac II site, 
                 TCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGG 
                   
               
               
                 (viral 
                 TAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGT 
                   
               
               
                 sequences in 
                 GGTGGCCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATCTGCGCTCTGCT 
                   
               
               
                 bold). CTA 
                 GAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAAC 
                   
               
               
                 = Leu 
                 CACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAA 
                   
               
               
                 changed to 
                 AAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGG 
                   
               
               
                 GCC = Ala 
                 AACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTC 
                   
               
               
                 (underlined). 
                 ACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGA 
                   
               
               
                   
                 GTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCG 
                   
               
               
                   
                 ATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTAC 
                   
               
               
                   
                 GATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCC 
                   
               
               
                   
                 ACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGA 
                   
               
               
                   
                 GCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGC 
                   
               
               
                   
                 CGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCC 
                   
               
               
                   
                 ATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCT 
                   
               
               
                   
                 CCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAG 
                   
               
               
                   
                 CGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTT 
                   
               
               
                   
                 ATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAA 
                   
               
               
                   
                 GATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTAT 
                   
               
               
                   
                 GCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACA 
                   
               
               
                   
                 TAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACT 
                   
               
               
                   
                 CTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCC 
                   
               
               
                   
                 AACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAG 
                   
               
               
                   
                 GAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAAT 
                   
               
               
                   
                 ACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCAT 
                   
               
               
                   
                 GAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCG 
                   
               
               
                   
                 CACATTTCCCCGAAAAGTGCCACCTGACGTCTAAGAAACCATTATTATCATGACA 
                   
               
               
                   
                 TTAACCTATAAAAATAGGCGTATCACGAGGCCCTTTCGTCTCGCGCGTTTCGGTG 
                   
               
               
                   
                 ATGACGGTGAAAACCTCTGACACATGCAGCTCCCGGAGACGGTCACAGCTTGTC 
                   
               
               
                   
                 TGTAAGCGGATGCCGGGAGCAGACAAGCCCGTCAGGGCGCGTCAGCGGGTGTT 
                   
               
               
                   
                 GGCGGGTGTCGGGGCTGGCTTAACTATGCGGCATCAGAGCAGATTGTACTGAG 
                   
               
               
                   
                 AGTGCACCATAAAATTGTAAACGTTAATATTTTGTTAAAATTCGCGTTAATTTTT 
                   
               
               
                   
                 GTTAAATCAGCTCATTTTTTAACCAATAGGCCGAAATCGGCAAAATCCCTTATAA 
                   
               
               
                   
                 ATCAAAAGAATAGCCCGAGATAGGGTTGAGTGTTGTTCCAGTTTGGAACAAGAG 
                   
               
               
                   
                 TCCACTATTAAAGAACGTGGACTCCAACGTCAAAGGGCGAAAAACCGTCTATCA 
                   
               
               
                   
                 GGGCGATGGCCCACTACGTGAACCATCACCCAAATCAAGTTTTTTGGGGTCGAG 
                   
               
               
                   
                 GTGCCGTAAAGCACTAAATCGGAACCCTAAAGGGAGCCCCCGATTTAGAGCTTG 
                   
               
               
                   
                 ACGGGGAAAGCCGGCGAACGTGGCGAGAAAGGAAGGGAAGAAAGCGAAAGG 
                   
               
               
                   
                 AGCGGGCGCTAGGGCGCTGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCA 
                   
               
               
                   
                 CACCCGCCGCGCTTAATGCGCCGCTACAGGGCGCGTACTATGGTTGCTTTGACG 
                   
               
               
                   
                 TATGCGGTGTGAAATACCGCACAGATGCGTAAGGAGAAAATACCGCATCAGGC 
                   
               
               
                   
                 GCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCGGTGCGGGCCT 
                   
               
               
                   
                 CTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTT 
                   
               
               
                   
                 GGGTAACGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGCCA 
                   
               
               
                   
                 AGCTTTAATACGACTCACTATAGGG ACCAAACAGAGAATCCGTGAGTTACGATA   
                   
               
               
                   
                 
                   AAAGGCGAAGGAGCAATTGAAGTCGCACGGGTAGAAGGTGTGAATCTCGAGT 
                 
                   
               
               
                   
                 
                   GCGAGCCCGAAGCACAAACTCGAGAAAGCCTTCTGCCAACATGTCTTCCGTATT 
                 
                   
               
               
                   
                 
                   TGATGAGTACGAACAGCTCCTCGCGGCTCAGACTCGCCCCAATGGAGCTCATG 
                 
                   
               
               
                   
                 
                   GAGGGGGAGAAAAAGGGAGTACCTTAAAAGTAGACGTCCCGGTATTCACTCT 
                 
                   
               
               
                   
                 
                   TAACAGTGATGACCCAGAAGATAGATGGAGCTTTGTGGTATTCTGCCTCCGGA 
                 
                   
               
               
                   
                 
                   TTGCTGTTAGCGAAGATGCCAACAAACCACTCAGGCAAGGTGCTCTCATATCTC 
                 
                   
               
               
                   
                 
                   TTTTATGCTCCCACTCACAGGTAATGAGGAACCATGTTGCCCTTGCAGGGAAAC 
                 
                   
               
               
                   
                 
                   AGAATGAAGCCACATTGGCCGTGCTTGAGATTGATGGCTTTGCCAACGGCACG 
                 
                   
               
               
                   
                 
                   CCCCAGTTCAACAATAGGAGTGGAGTGTCTGAAGAGAGAGCACAGAGATTTG 
                 
                   
               
               
                   
                 
                   CGATGATAGCAGGATCTCTCCCTCGGGCATGCAGCAACGGAACCCCGTTCGTC 
                 
                   
               
               
                   
                 
                   ACAGCCGGGGCCGAAGATGATGCACCAGAAGACATCACCGATACCCTGGAGA 
                 
                   
               
               
                   
                 
                   GGATCCTCTCTATCCAGGCTCAAGTATGGGTCACAGTAGCAAAAGCCATGACT 
                 
                   
               
               
                   
                 
                   GCGTATGAGACTGCAGATGAGTCGGAAACAAGGCGAATCAATAAGTATATGC 
                 
                   
               
               
                   
                 
                   AGCAAGGCAGGGTCCAAAAGAAATACATCCTCTACCCCGTATGCAGGAGCACA 
                 
                   
               
               
                   
                 
                   ATCCAACTCACGATCAGACAGTCTCTTGCAGTCCGCATCTTTTTGGTTAGCGAG 
                 
                   
               
               
                   
                 
                   CTCAAGAGAGGCCGCAACACGGCAGGTGGTACCTCTACTTATTATAACCTGGT 
                 
                   
               
               
                   
                 
                   AGGGGACGTAGACTCATACATCAGGAATACCGGGCTTACTGCATTCTTCTTGAC 
                 
                   
               
               
                   
                 
                   ACTCAAGTACGGAATCAACACCAAGACATCAGCCCTTGCACTTAGTAGCCTCTC 
                 
                   
               
               
                   
                 
                   AGGCGACATCCAGAAGATGAAGCAGCTCATGCGTTTGTATCGGATGAAAGGA 
                 
                   
               
               
                   
                 
                   GATAATGCGCCGTACATGACATTACTTGGTGATAGTGACCAGATGAGCTTTGC 
                 
                   
               
               
                   
                 
                   GCCTGCCGAGTATGCACAACTTTACTCCTTTGCCATGGGTATGGCATCAGTCCT 
                 
                   
               
               
                   
                 
                   AGATAAAGGTACTGGGAAATACCAATTTGCCAGGGACTTTATGAGCACATCAT 
                 
                   
               
               
                   
                 
                   TCTGGAGACTTGGAGTAGAGTACGCTCAGGCTCAGGGAAGTAGCATTAACGA 
                 
                   
               
               
                   
                 
                   GGATATGGCTGCCGAGCTAAAGCTAACCCCAGCAGCAAGGAGGGGCCTGGCA 
                 
                   
               
               
                   
                 
                   GCTGCTGCCCAACGGGTCTCCGAGGAGACCAGCAGCATAGACATGCCTACTCA 
                 
                   
               
               
                   
                 
                   ACAAGTCGGAGTCCTCACTGGGCTTAGCGAGGGGGGGTCCCAAGCTCTACAAG 
                 
                   
               
               
                   
                 
                   GCGGATCGAATAGATCGCAAGGGCAACCAGAAGCCGGGGATGGGGAGACCC 
                 
                   
               
               
                   
                 
                   AATTCCTGGATCTGATGAGAGCGGTAGCAAATAGCATGAGGGAGGCGCCAAA 
                 
                   
               
               
                   
                 
                   CTCTGCACAGGGCACTCCCCAATCGGGGCCTCCCCCAACTCCTGGGCCATCCCA 
                 
                   
               
               
                   
                 
                   AGATAACGACACCGACTGGGGGTATTGATGGACAAAACCCAGCCTGCTTCCAC 
                 
                   
               
               
                   
                 
                   AAAAACATCCCAATGCCCTCACCCGTAGTCGACCCCTCGATTTGCGGCTCTATAT 
                 
                   
               
               
                   
                 
                   GACCACACCCTCAAACAAACATCCCCCTCTTTCCTCCCTCCCCCTGCTGTACAACT 
                 
                   
               
               
                   
                 
                   ACGTACGCCCTAGATACCACAGGCACAATGCGGCTCACTAACAATCAAAACAG 
                 
                   
               
               
                   
                 
                   AGCCGAGGGAATTAGAAAAAAGTACGGGTAGAAGAGGGATATTCAGAGATC 
                 
                   
               
               
                   
                 
                   AGGGCAAGTCTCCCGAGTCTCTGCTCTCTCCTCTACCTGATAGACCAGGACAAA 
                 
                   
               
               
                   
                 
                   CATGGCCACCTTTACAGATGCAGAGATCGACGAGCTATTTGAGACAAGTGGAA 
                 
                   
               
               
                   
                 
                   CTGTCATTGACAACATAATTACAGCCCAGGGTAAACCAGCAGAGACTGTTGGA 
                 
                   
               
               
                   
                 
                   AGGAGTGCAATCCCACAAGGCAAGACCAAGGTGCTGAGCGCAGCATGGGAGA 
                 
                   
               
               
                   
                 
                   AGCATGGGAGCATCCAGCCACCGGCCAGTCAAGACAACCCCGATCGACAGGA 
                 
                   
               
               
                   
                 
                   CAGATCTGACAAACAACCATCCACACCCGAGCAAACGACCCCGCATGACAGCC 
                 
                   
               
               
                   
                 
                   CGCCGGCCACATCCGCCGACCAGCCCCCCACCCAGGCCACAGACGAAGCCGTC 
                 
                   
               
               
                   
                 
                   GACACACAGCTCAGGACCGGAGCAAGCAACTCTCTGCTGTTGATGCTTGACAA 
                 
                   
               
               
                   
                 
                   GCTCAGCAATAAATCGTCCAATGCTAAAAAGGGCCCATGGTCGAGCCCCCAAG 
                 
                   
               
               
                   
                 
                   AGGGGAATCACCAACGTCCGACTCAACAGCAGGGGAGTCAACCCAGTCGCGG 
                 
                   
               
               
                   
                 
                   AAACAGTCAGGAAAGACCGCAGAACCAAGTCAAGGCCGCCCCTGGAAACCAG 
                 
                   
               
               
                   
                 
                   GGCACAGACGTGAACACAGCATATCATGGACAATGGGAGGAGTCACAACTAT 
                 
                   
               
               
                   
                 
                   CAGCTGGTGCAACCCCTCATGCTCTCCGATCAAGGCAGAGCCAAGACAATACC 
                 
                   
               
               
                   
                 
                   CTTGTATCTGCGGATCATGTCCAGCCACCTGTAGACTTTGTGCAAGCGATGATG 
                 
                   
               
               
                   
                 
                   TCTATGATGGAGGCGATATCACAGAGAGTAAGTAAGGTTGACTATCAGCTAGA 
                 
                   
               
               
                   
                 
                   TCTTGTCTTGAAACAGACATCCTCCATCCCTATGATGCGGTCCGAAATCCAACA 
                 
                   
               
               
                   
                 
                   GCTGAAAACATCTGTTGCAGTCATGGAAGCCAACTTGGGAATGATGAAGATTC 
                 
                   
               
               
                   
                 
                   TGGATCCCGGTTGTGCCAACATTTCATCTCTGAGTGATCTACGGGCAGTTGCCC 
                 
                   
               
               
                   
                 
                   GATCTCACCCGGTTTTAGTTTCAGGCCCTGGAGACCCCTCTCCCTATGTGACACA 
                 
                   
               
               
                   
                 
                   AGGAGGCGAAATGGCACTTAATAAACTTTCGCAACCAGTGCCACATCCATCTG 
                 
                   
               
               
                   
                 
                   AATTGATTAAACCCGCCACTGCATGCGGGCCTGATATAGGAGTGGAAAAGGA 
                 
                   
               
               
                   
                 
                   CACTGTCCGTGCATTGATCATGTCACGCCCAATGCACCCGAGTTCTTCAGCCAA 
                 
                   
               
               
                   
                 
                   GCTCCTAAGCAAGTTAGATGCAGCCGGGTCGATCGAGGAAATCAGGAAAATC 
                 
                   
               
               
                   
                 
                   AAGCGCCTTGCTCTAAATGGCTAATTACTACTGCCACACGTAGCGGGTCCCTGT 
                 
                   
               
               
                   
                   CCACTCGGCATCACACGGAATCTGCACCGAGTTCCCCC     CCGCGG   TTAGAAAAAA 
                   
               
               
                   
                 TACGGGTAGAACCGCCACCATGCATCTGCTGTGTTTCCTGTCGCTCGCCTGCTCA 
                   
               
               
                   
                 CTGCTGGCGGCGGCACTTATCCCGTCCCCACGGGAGGCTCCTGCCACCGTGGCC 
                   
               
               
                   
                 GCCTTCGAATCTGGGCTGGGCTTCAGCGAAGCCGAGCCCGATGGCGGAGAGGT 
                   
               
               
                   
                 CAAGGCATTCGAAGGAAAGGACCTCGAAGAACAGCTGAGATCCGTGTCCTCCGT 
                   
               
               
                   
                 GGACGAACTCATGTCCGTCCTGTACCCCGATTACTGGAAGATGTACAAATGCCA 
                   
               
               
                   
                 GCTCCGGAAGGGCGGTTGGCAGCAGCCCACTCTGAACACTCGCACGGGAGATT 
                   
               
               
                   
                 CCGTGAAGTTTGCCGCCGCCCACTACAATACTGAGATTCTCAAGTCCATCGACAA 
                   
               
               
                   
                 CGAATGGAGGAAAACCCAGTGTATGCCGCGCGAAGTCTGCATTGACGTGGGAA 
                   
               
               
                   
                 AGGAGTTCGGCGCTGCCACCAACACCTTCTTTAAGCCTCCCTGCGTGTCGGTGTA 
                   
               
               
                   
                 TCGCTGCGGGGGATGCTGCAACAGCGAAGGCCTTCAGTGCATGAACACCAGCA 
                   
               
               
                   
                 CCGGATACCTCAGCAAGACTCTCTTCGAAATCACTGTGCCGCTGTCACAAGGCCC 
                   
               
               
                   
                 GAAGCCTGTGACCATTTCCTTCGCCAACCACACCTCCTGTCGGTGCATGAGCAAG 
                   
               
               
                   
                 CTGGATGTGTACAGACAGGTGCACTCCATCATCCGGAGATCGTTGCCTGCCACC 
                   
               
               
                   
                 CTGCCGCAGTGCCAAGCGGCTAACAAGACCTGTCCCACCAACTACGTGTGGAAC 
                   
               
               
                   
                 AACTATATGTGTCGGTGCCTGGCACAGCAGGACTTTATCTTCTACTCCAACGTGG 
                   
               
               
                   
                 AGGACGACTCGACTAACGGTTTCCACGACGTGTGCGGACCCAACAAGGAGCTG 
                   
               
               
                   
                 GATGAGGATACTTGTCAGTGCGTGTGCAAGGGTGGCCTGCGCCCGTCCTCCTGC 
                   
               
               
                   
                 GGACCACATAAGGAACTGGACAGGGACTCGTGCCAATGCGTCTGCAAGAACAA 
                   
               
               
                   
                 GCTGTTCCCTAACTCCTGCGGGGCGAACCGCGAATTCGACGAGAACACCTGTCA 
                   
               
               
                   
                 GTGTGTGTGCAAGCGGACTTGCCCGAGGAATCAGCCTCTTAACCCCGGAAAATG 
                   
               
               
                   
                 CGCCTGCGAATGCACAGAGAACACCCAGAAGTGCTTCTTGAAAGGGAAGAAGT 
                   
               
               
                   
                 TCCACCACCAAACCTGTTCATGCTACCGGCGCCCATGTGCCAACCGGCTGAAGCA 
                   
               
               
                   
                 CTGCGACCCGGGATTGAGCTTCAGCGAGGAGGTCTGCAGATGCGTGCCGTCATA 
                   
               
               
                   
                 CTGGAAGCGACCTCATCTGAATTAGCccgcgg ACCCAAGGTCCAACTCTCCAAGC   
                   
               
               
                   
                 
                   GGCAATCCTCTCTCGCTTCCTCAGCCCCACTGAATGATCGCGTAACCGTAATTAA 
                 
                   
               
               
                   
                 
                   TCTAGCTACATTTAAGATTAAGAAAAAATACGGGTAGAATTGGAGTGCCCCAA 
                 
                   
               
               
                   
                 
                   TTGTGCCAAGATGGACTCATCTAGGACAATTGGGCTGTACTTTGATTCTGCCCA 
                 
                   
               
               
                   
                 
                   TTCTTCTAGCAACCTGTTAGCATTTCCGATCGTCCTACAAGACACAGGAGATGG 
                 
                   
               
               
                   
                 
                   GAAGAAGCAAATCGCCCCGCAATATAGGATCCAGCGCCTTGACTTGTGGACTG 
                 
                   
               
               
                   
                 
                   ATAGTAAGGAGGACTCAGTATTCATCACCACCTATGGATTCATCTTTCAAGTTG 
                 
                   
               
               
                   
                 
                   GGAATGAAGAAGCCACCGTCGGCATGATCGATGATAAACCCAAGCGCGAGTT 
                 
                   
               
               
                   
                 
                   ACTTTCCGCTGCGATGCTCTGCCTAGGAAGCGTCCCAAATACCGGAGACCTTAT 
                 
                   
               
               
                   
                 
                   TGAGCTGGCAAGGGCCTGTCTCACTATGATAGTCACATGCAAGAAGAGTGCAA 
                 
                   
               
               
                   
                 
                   CTAATACTGAGAGAATGGTTTTCTCAGTAGTGCAGGCACCCCAAGTGCTGCAA 
                 
                   
               
               
                   
                 
                   AGCTGTAGGGTTGTGGCAAACAAATACTCATCAGTGAATGCAGTCAAGCACGT 
                 
                   
               
               
                   
                 
                   GAAAGCGCCAGAGAAGATTCCCGGGAGTGGAACCCTAGAATACAAGGTGAAC 
                 
                   
               
               
                   
                 
                   TTTGTCTCCTTGACTGTGGTACCGAAGAGGGATGTCTACAAGATCCCAGCTGCA 
                 
                   
               
               
                   
                 
                   GTATTGAAGGTTTCTGGCTCGAGTCTGTACAATCTTGCGCTCAATGTCACTATT 
                 
                   
               
               
                   
                 
                   AATGTGGAGGTAGACCCGAGGAGTCCTTTGGTTAAATCTCTGTCTAAGTCTGA 
                 
                   
               
               
                   
                 
                   CAGCGGATACTATGCTAACCTCTTCTTGCATATTGGACTTATGACCACTGTAGA 
                 
                   
               
               
                   
                 
                   TAGGAAGGGGAAGAAAGTGACATTTGACAAGCTGGAAAAGAAAATAAGGAG 
                 
                   
               
               
                   
                 
                   CCTTGATCTATCTGTCGGGCTCAGTGATGTGCTCGGGCCTTCCGTGTTGGTAAA 
                 
                   
               
               
                   
                 
                   AGCAAGAGGTGCACGGACTAAGCTTTTGGCACCTTTCTTCTCTAGCAGTGGGA 
                 
                   
               
               
                   
                 
                   CAGCCTGCTATCCCATAGCAAATGCTTCTCCTCAGGTGGCCAAGATACTCTGGA 
                 
                   
               
               
                   
                 
                   GTCAAACCGCGTGCCTGCGGAGCGTTAAAATCATTATCCAAGCAGGTACCCAA 
                 
                   
               
               
                   
                 
                   CGCGCTGTCGCAGTGACCGCCGACCACGAGGTTACCTCTACTAAGCTGGAGAA 
                 
                   
               
               
                   
                 
                   GGGGCACACCCTTGCCAAATACAATCCTTTTAAGAAATAAGCTGCGTCTCTGAG 
                 
                   
               
               
                   
                 
                   ATTGCGCTCCGCCCACTCACCCAGATCATCATGACACAAAAAACTAATCTGTCTT 
                 
                   
               
               
                   
                 
                   GATTATTTACAGTTAGTTTACCTGTCTATCAAGTTAGAAAAAACACGGGTAGAA 
                 
                   
               
               
                   
                 
                   GATTCTGGATCCCGGTTGGCGCCCTCCAGGTGCAAGATGGGCTCCAGACCTTCT 
                 
                   
               
               
                   
                 
                   ACCAAGAACCCAGCACCTATGATGCTGACTATCCGGGTTGCGCTGGTACTGAG 
                 
                   
               
               
                   
                 
                   TTGCATCTGTCCGGCAAACTCCATTGATGGCAGGCCTCTTGCAGCTGCAGGAAT 
                 
                   
               
               
                   
                 
                   TGTGGTTACAGGAGACAAAGCCGTCAACATATACACCTCATCCCAGACAGGAT 
                 
                   
               
               
                   
                 
                   CAATCATAGTTAAGCTCCTCCCGAATCTGCCCAAGGATAAGGAGGCATGTGCG 
                 
                   
               
               
                   
                 
                   AAAGCCCCCTTGGATGCATACAACAGGACATTGACCACTTTGCTCACCCCCCTT 
                 
                   
               
               
                   
                 
                   GGTGACTCTATCCGTAGGATACAAGAGTCTGTGACTACATCTGGAGGGGGGA 
                 
                   
               
               
                   
                 
                   GACAGGGGCGCCTTATAGGCGCCATTATTGGCGGTGTGGCTCTTGGGGTTGCA 
                 
                   
               
               
                   
                 
                   ACTGCCGCACAAATAACAGCGGCCGCAGCTCTGATACAAGCCAAACAAAATGC 
                 
                   
               
               
                   
                 
                   TGCCAACATCCTCCGACTTAAAGAGAGCATTGCCGCAACCAATGAGGCTGTGC 
                 
                   
               
               
                   
                 
                   ATGAGGTCACTGACGGATTATCGCAACTAGCAGTGGCAGTTGGGAAGATGCA 
                 
                   
               
               
                   
                 
                   GCAGTTTGTTAATGACCAATTTAATAAAACAGCTCAGGAATTAGACTGCATCA 
                 
                   
               
               
                   
                 
                   AAATTGCACAGCAAGTTGGTGTAGAGCTCAACCTGTACCTAACCGAATTGACT 
                 
                   
               
               
                   
                 
                   ACAGTATTCGGACCACAAATCACTTCACCTGCTTTAAACAAGCTGACTATTCAG 
                 
                   
               
               
                   
                 
                   GCACTTTACAATCTAGCTGGTGGAAATATGGATTACTTATTGACTAAGTTAGGT 
                 
                   
               
               
                   
                 
                   GTAGGGAACAATCAACTCAGCTCATTAATCGGTAGCGGCTTAATCACCGGTAA 
                 
                   
               
               
                   
                 
                   CCCTATTCTATACGACTCACAGACTCAACTCTTGGGTATACAGGTAACT 
                   
                     
                     
                         
                         
                     
                   
                   CCT 
                 
                   
               
               
                   
                 
                   TCAGTCGGGAACCTAAATAATATGCGTGCCACCTACTTGGAAACCTTATCCGTA 
                 
                   
               
               
                   
                 
                   AGCACAACCAGGGGATTTGCCTCGGCACTTGTCCCAAAAGTGGTGACACAGGT 
                 
                   
               
               
                   
                 
                   CGGTTCTGTGATAGAAGAACTTGACACCTCATACTGTATAGAAACTGACTTAG 
                 
                   
               
               
                   
                 
                   ATTTATATTGTACAAGAATAGTAACGTTCCCTATGTCCCCTGGTATTTATTCCTG 
                 
                   
               
               
                   
                 
                   CTTGAGCGGCAATACGTCGGCCTGTATGTACTCAAAGACCGAAGGCGCACTTA 
                 
                   
               
               
                   
                 
                   CTACACCATACATGACTATCAAAGGTTCAGTCATCGCCAACTGCAAGATGACAA 
                 
                   
               
               
                   
                 
                   CATGTAGATGTGTAAACCCCCCGGGTATCATATCGCAAAACTATGGAGAAGCC 
                 
                   
               
               
                   
                 
                   GTGTCTCTAATAGATAAACAATCATGCAATGTTTTATCCTTAGGCGGGATAACT 
                 
                   
               
               
                   
                 
                   TTAAGGCTCAGTGGGGAATTCGATGTAACTTATCAGAAGAATATCTCAATACA 
                 
                   
               
               
                   
                 
                   AGATTCTCAAGTAATAATAACAGGCAATCTTGATATCTCAACTGAGCTTGGGA 
                 
                   
               
               
                   
                 
                   ATGTCAACAACTCGATCAGTAATGCTTTGAATAAGTTAGAGGAAAGCAACAGA 
                 
                   
               
               
                   
                 
                   AAACTAGACAAAGTCAATGTCAAACTGACTAGCACATCTGCTCTCATTACCTAT 
                 
                   
               
               
                   
                 
                   ATCGTTTTGACTATCATATCTCTTGTTTTTGGTATACTTAGCCTGATTCTAGCATG 
                 
                   
               
               
                   
                 
                   CTACCTAATGTACAAGCAAAAGGCGCAACAAAAGACCTTATTATGGCTTGGGA 
                 
                   
               
               
                   
                 
                   ATAATACTCTAGATCAGATGAGAGCCACTACAAAAATGTGAACACAGATGAG 
                 
                   
               
               
                   
                 
                   GAACGAAGGTTTCCCTAATAGTAATTTGTGTGAAAGTTCTGGTAGTCTGTCAGT 
                 
                   
               
               
                   
                 
                   TCAGAGAGTTAAGAAAAAACTACCGGTTGTAGATGACCAAAGGACGATATAC 
                 
                   
               
               
                   
                 
                   GGGTAGAACGGTAAGAGAGGCCGCCCCTCAATTGCGAGCCAGGCTTCACAACC 
                 
                   
               
               
                   
                 
                   TCCGTTCTACCGCTTCACCGACAACAGTCCTCAATCATGGACCGCGCCGTTAGC 
                 
                   
               
               
                   
                 
                   CAAGTTGCGTTAGAGAATGATGAAAGAGAGGCAAAAAATACATGGCGCTTGA 
                 
                   
               
               
                   
                 
                   TATTCCGGATTGCAATCTTATTCTTAACAGTAGTGACCTTGGCTATATCTGTAGC 
                 
                   
               
               
                   
                 
                   CTCCCTTTTATATAGCATGGGGGCTAGCACACCTAGCGATCTTGTAGGCATACC 
                 
                   
               
               
                   
                 
                   GACTAGGATTTCCAGGGCAGAAGAAAAGATTACATCTACACTTGGTTCCAATC 
                 
                   
               
               
                   
                 
                   AAGATGTAGTAGATAGGATATATAAGCAAGTGGCCCTTGAGTCTCCGTTGGCA 
                 
                   
               
               
                   
                 
                   TTGTTAAATACTGAGACCACAATTATGAACGCAATAACATCTCTCTCTTATCAG 
                 
                   
               
               
                   
                 
                   ATTAATGGAGCTGCAAACAACAGTGGGTGGGGGGCACCTATCCATGACCCAG 
                 
                   
               
               
                   
                 
                   ATTATATAGGGGGGATAGGCAAAGAACTCATTGTAGATGATGCTAGTGATGTC 
                 
                   
               
               
                   
                 
                   ACATCATTCTATCCCTCTGCATTTCAAGAACATCTGAATTTTATCCCGGCGCCTA 
                 
                   
               
               
                   
                 
                   CTACAGGATCAGGTTGCACTCGAATACCCTCATTTGACATGAGTGCTACCCATT 
                 
                   
               
               
                   
                 
                   ACTGCTACACCCATAATGTAATATTGTCTGGATGCAGAGATCACTCACATTCAT 
                 
                   
               
               
                   
                 
                   ATCAGTATTTAGCACTTGGTGTGCTCCGGACATCTGCAACAGGGAGGGTATTCT 
                 
                   
               
               
                   
                 
                   TTTCTACTCTGCGTTCCATCAACCTGGACGACACCCAAAATCGGAAGTCTTGCA 
                 
                   
               
               
                   
                 
                   GTGTGAGTGCAACTCCCCTGGGTTGTGATATGCTGTGCTCGAAAGTCACGGAG 
                 
                   
               
               
                   
                 
                   ACAGAGGAAGAAGATTATAACTCAGCTGTCCCTACGCGGATGGTACATGGGA 
                 
                   
               
               
                   
                 
                   GGTTAGGGTTCGACGGCCAGTACCACGAAAAGGACCTAGATGTCACAACATTA 
                 
                   
               
               
                   
                 
                   TTCGGGGACTGGGTGGCCAACTACCCAGGAGTAGGGGGTGGATCTTTTATTGA 
                 
                   
               
               
                   
                 
                   CAGCCGCGTATGGTTCTCAGTCTACGGAGGGTTAAAACCCAATTCACCCAGTG 
                 
                   
               
               
                   
                 
                   ACACTGTACAGGAAGGGAAATATGTGATATACAAGCGATACAATGACACATG 
                 
                   
               
               
                   
                 
                   CCCAGATGAGCAAGACTACCAGATTCGAATGGCCAAGTCTTCGTATAAGCCTG 
                 
                   
               
               
                   
                 
                   GACGGTTTGGTGGGAAACGCATACAGCAGGCTATCTTATCTATCAAGGTGTCA 
                 
                   
               
               
                   
                 
                   ACATCCTTAGGCGAAGACCCGGTACTGACTGTACCGCCCAACACAGTCACACTC 
                 
                   
               
               
                   
                 
                   ATGGGGGCCGAAGGCAGAATTCTCACAGTAGGGACATCTCATTTCTTGTATCA 
                 
                   
               
               
                   
                 
                   ACGAGGGTCATCATACTTCTCTCCCGCGTTATTATATCCTATGACAGTCAGCAAC 
                 
                   
               
               
                   
                 
                   AAAACAGCCACTCTTCATAGTCCTTATACATTCAATGCCTTCACTCGGCCAGGTA 
                 
                   
               
               
                   
                 
                   GTATCCCTTGCCAGGCTTCAGCAAGATGCCCCAACTCGTGTGTTACTGGAGTCT 
                 
                   
               
               
                   
                 
                   ATACAGATCCATATCCCCTAATCTTCTATAGAAACCACACCTTGCGAGGGGTAT 
                 
                   
               
               
                   
                 
                   TCGGGACAATGCTTGATGGTGTACAAGCAAGACTTAACCCTGCGTCTGCAGTA 
                 
                   
               
               
                   
                 
                   TTCGATAGCACATCCCGCAGTCGCATTACTCGAGTGAGTTCAAGCAGTACCAAA 
                 
                   
               
               
                   
                 
                   GCAGCATACACAACATCAACTTGTTTTAAAGTGGTCAAGACTAATAAGACCTAT 
                 
                   
               
               
                   
                 
                   TGTCTCAGCATTGCTGAAATATCTAATACTCTCTTCGGAGAATTCAGAATCGTCC 
                 
                   
               
               
                   
                 
                   CGTTACTAGTTGAGATCCTCAAAGATGACGGGGTTAGAGAAGCCAGGTCTGGC 
                 
                   
               
               
                   
                 
                   TAGTTGAGTCAATTATAAAGGAGTTGGAAAGATGGCATTGTATCACCTATCTTC 
                 
                   
               
               
                   
                 
                   TGCGACATCAAGAATCAAACCGAATGCCGGCGCGTGCTCGAATTCCATGTTGC 
                 
                   
               
               
                   
                 
                   CAGTTGACCACAATCAGCCAGTGCTCATGCGATCAGATTAAGCCTTGTCAATAG 
                 
                   
               
               
                   
                 
                   TCTCTTGATTAAGAAAAAATGTAAGTGGCAATGAGATACAAGGCAAAACAGCT 
                 
                   
               
               
                   
                 
                   CATGGTTAACAATACGGGTAGGACATGGCGAGCTCCGGTCCTGAAAGGGCAG 
                 
                   
               
               
                   
                 
                   AGCATCAGATTATCCTACCAGAGTCACACCTGTCTTCACCATTGGTCAAGCACA 
                 
                   
               
               
                   
                 
                   AACTACTCTATTACTGGAAATTAACTGGGCTACCGCTTCCTGATGAATGTGACT 
                 
                   
               
               
                   
                 
                   TCGACCACCTCATTCTCAGCCGACAATGGAAAAAAATACTTGAATCGGCCTCTC 
                 
                   
               
               
                   
                 
                   CTGATACTGAGAGAATGATAAAACTCGGAAGGGCAGTACACCAAACTCTTAAC 
                 
                   
               
               
                   
                 
                   CACAATTCCAGAATAACCGGAGTGCTCCACCCCAGGTGTTTAGAAGAACTGGC 
                 
                   
               
               
                   
                 
                   TAATATTGAGGTCCCAGATTCAACCAACAAATTTCGGAAGATTGAGAAGAAGA 
                 
                   
               
               
                   
                 
                   TCCAAATTCACAACACGAGATATGGAGAACTGTTCACAAGGCTGTGTACGCAT 
                 
                   
               
               
                   
                 
                   ATAGAGAAGAAACTGCTGGGGTCATCTTGGTCTAACAATGTCCCCCGGTCAGA 
                 
                   
               
               
                   
                 
                   GGAGTTCAGCAGCATTCGTACGGATCCGGCATTCTGGTTTCACTCAAAATGGTC 
                 
                   
               
               
                   
                 
                   CACAGCCAAGTTTGCATGGCTCCATATAAAACAGATCCAGAGGCATCTGATGG 
                 
                   
               
               
                   
                 
                   TGGCAGCTAGGACAAGGTCTGCGGCCAACAAATTGGTGATGCTAACCCATAAG 
                 
                   
               
               
                   
                 
                   GTAGGCCAAGTCTTTGTCACTCCTGAACTTGTCGTTGTGACGCATACGAATGAG 
                 
                   
               
               
                   
                 
                   AACAAGTTCACATGTCTTACCCAGGAACTTGTATTGATGTATGCAGATATGATG 
                 
                   
               
               
                   
                 
                   GAGGGCAGAGATATGGTCAACATAATATCAACCACGGCGGTGCATCTCAGAA 
                 
                   
               
               
                   
                 
                   GCTTATCAGAGAAAATTGATGACATTTTGCGGTTAATAGACGCTCTGGCAAAA 
                 
                   
               
               
                   
                 
                   GACTTGGGTAATCAAGTCTACGATGTTGTATCACTAATGGAGGGATTTGCATA 
                 
                   
               
               
                   
                 
                   CGGAGCTGTCCAGCTACTCGAGCCGTCAGGTACATTTGCAGGAGATTTCTTCGC 
                 
                   
               
               
                   
                 
                   ATTCAACCTGCAGGAGCTTAAAGACATTCTAATTGGCCTCCTCCCCAATGATAT 
                 
                   
               
               
                   
                 
                   AGCAGAATCCGTGACTCATGCAATCGCTACTGTATTCTCTGGTTTAGAACAGAA 
                 
                   
               
               
                   
                 
                   TCAAGCAGCTGAGATGTTGTGTCTGTTGCGTCTGTGGGGTCACCCACTGCTTGA 
                 
                   
               
               
                   
                 
                   GTCCCGTATTGCAGCAAAGGCAGTCAGGAGCCAAATGTGCGCACCGAAAATG 
                 
                   
               
               
                   
                 
                   GTAGACTTTGATATGATCCTTCAGGTACTGTCTTTCTTCAAGGGAACAATCATC 
                 
                   
               
               
                   
                 
                   AACGGGTACAGAAAGAAGAATGCAGGTGTGTGGCCGCGAGTCAAAGTGGAT 
                 
                   
               
               
                   
                 
                   ACAATATATGGGAAGGTCATTGGGCAACTACATGCAGATTCAGCAGAGATTTC 
                 
                   
               
               
                   
                 
                   ACACGATATCATGTTGAGAGAGTATAAGAGTTTATCTGCACTTGAATTTGAGCC 
                 
                   
               
               
                   
                 
                   ATGTATAGAATATGACCCTGTCACCAACCTGAGCATGTTCCTAAAAGACAAGG 
                 
                   
               
               
                   
                 
                   CAATCGCACACCCCAACGATAATTGGCTTGCCTCGTTTAGGCGGAACCTTCTCT 
                 
                   
               
               
                   
                 
                   CCGAAGACCAGAAGAAACATGTAAAAGAAGCAACTTCGACTAATCGCCTCTTG 
                 
                   
               
               
                   
                 
                   ATAGAGTTTTTAGAGTCAAATGATTTTGATCCATATAAAGAGATGGAATATCT 
                 
                   
               
               
                   
                 
                   GACGACCCTTGAGTACCTTAGAGATGACAATGTGGCAGTATCATACTCGCTCA 
                 
                   
               
               
                   
                 
                   AGGAGAAGGAAGTGAAAGTTAATGGACGGATCTTCGCTAAGCTGACAAAGAA 
                 
                   
               
               
                   
                 
                   GTTAAGGAACTGTCAGGTGATGGCGGAAGGGATCCTAGCCGATCAGATTGCA 
                 
                   
               
               
                   
                 
                   CCTTTCTTTCAGGGAAATGGAGTCATTCAGGATAGCATATCCTTGACCAAGAGT 
                 
                   
               
               
                   
                 
                   ATGCTAGCGATGAGTCAACTGTCTTTTAACAGCAATAAGAAACGTATCACTGA 
                 
                   
               
               
                   
                 
                   CTGTAAAGAAAGAGTATCTTCAAACCGCAATCATGATCCGAAAAGCAAGAACC 
                 
                   
               
               
                   
                 
                   GTCGGAGAGTTGCAACCTTCATAACAACTGACCTGCAAAAGTACTGTCTTAATT 
                 
                   
               
               
                   
                 
                   GGAGATATCAGACAATCAAATTGTTCGCTCATGCCATCAATCAGTTGATGGGC 
                 
                   
               
               
                   
                 
                   CTACCTCACTTCTTCGAATGGATTCACCTAAGACTGATGGACACTACGATGTTC 
                 
                   
               
               
                   
                 
                   GTAGGAGACCCTTTCAATCCTCCAAGTGACCCTACTGACTGTGACCTCTCAAGA 
                 
                   
               
               
                   
                 
                   GTCCCTAATGATGACATATATATTGTCAGTGCCAGAGGGGGTATCGAAGGATT 
                 
                   
               
               
                   
                 
                   ATGCCAGAAGCTATGGACAATGATCTCAATTGCTGCAATCCAACTTGCTGCAGC 
                 
                   
               
               
                   
                 
                   TAGATCGCATTGTCGTGTTGCCTGTATGGTACAGGGTGATAATCAAGTAATAG 
                 
                   
               
               
                   
                 
                   CAGTAACGAGAGAGGTAAGATCAGACGACTCTCCGGAGATGGTGTTGACACA 
                 
                   
               
               
                   
                 
                   GTTGCATCAAGCCAGTGATAATTTCTTCAAGGAATTAATTCATGTCAATCATTT 
                 
                   
               
               
                   
                 
                   GATTGGCCATAATTTGAAGGATCGTGAAACCATCAGGTCAGACACATTCTTCAT 
                 
                   
               
               
                   
                 
                   ATACAGCAAACGAATCTTCAAAGATGGAGCAATCCTCAGTCAAGTCCTCAAAA 
                 
                   
               
               
                   
                 
                   ATTCATCTAAATTAGTGCTAGTGTCAGGTGATCTCAGTGAAAACACCGTAATGT 
                 
                   
               
               
                   
                 
                   CCTGTGCCAACATTGCCTCTACTGTAGCACGGCTATGCGAGAACGGGCTTCCCA 
                 
                   
               
               
                   
                 
                   AAGACTTCTGTTACTATTTAAACTATATAATGAGTTGTGTGCAGACATACTTTG 
                 
                   
               
               
                   
                 
                   ACTCTGAGTTCTCCATCACCAACAATTCGCACCCCGATCTTAATCAGTCGTGGAT 
                 
                   
               
               
                   
                 
                   TGAGGACATCTCTTTTGTGCACTCATATGTTCTGACTCCTGCCCAATTAGGGGG 
                 
                   
               
               
                   
                 
                   ACTGAGTAACCTTCAATACTCAAGGCTCTACACTAGAAATATCGGTGACCCGG 
                 
                   
               
               
                   
                 
                   GGACTACTGCTTTTGCAGAGATCAAGCGACTAGAAGCAGTGGGATTACTGAGT 
                 
                   
               
               
                   
                 
                   CCTAACATTATGACTAATATCTTAACTAGGCCGCCTGGGAATGGAGATTGGGC 
                 
                   
               
               
                   
                 
                   CAGTCTGTGCAACGACCCATACTCTTTCAATTTTGAGACTGTTGCAAGCCCAAA 
                 
                   
               
               
                   
                 
                   TATTGTTCTTAAGAAACATACGCAAAGAGTCCTATTTGAAACTTGTTCAAATCC 
                 
                   
               
               
                   
                 
                   CTTATTGTCTGGAGTGCACACAGAGGATAATGAGGCAGAAGAGAAGGCATTG 
                 
                   
               
               
                   
                 
                   GCTGAATTCTTGCTTAATCAAGAGGTGATTCATCCCCGCGTTGCGCATGCCATC 
                 
                   
               
               
                   
                 
                   ATGGAGGCAAGCTCTGTAGGTAGGAGAAAGCAAATTCAAGGGCTTGTTGACA 
                 
                   
               
               
                   
                 
                   CAACAAACACCGTAATTAAGATTGCGCTTACTAGGAGGCCATTAGGCATCAAG 
                 
                   
               
               
                   
                 
                   AGGCTGATGCGGATAGTCAATTATTCTAGCATGCATGCAATGCTGTTTAGAGA 
                 
                   
               
               
                   
                 
                   CGATGTTTTTTCCTCCAGTAGATCCAACCACCCCTTAGTCTCTTCTAATATGTGTT 
                 
                   
               
               
                   
                 
                   CTCTGACACTGGCAGACTATGCACGGAATAGAAGCTGGTCACCTTTGACGGGA 
                 
                   
               
               
                   
                 
                   GGCAGGAAAATACTGGGTGTATCTAATCCTGATACGATAGAACTCGTAGAGG 
                 
                   
               
               
                   
                 
                   GTGAGATTCTTAGTGTAAGCGGAGGGTGTACAAGATGTGACAGCGGAGATGA 
                 
                   
               
               
                   
                 
                   ACAATTTACTTGGTTCCATCTTCCAAGCAATATAGAATTGACCGATGACACCAG 
                 
                   
               
               
                   
                 
                   CAAGAATCCTCCGATGAGGGTACCATATCTCGGGTCAAAGACACAGGAGAGG 
                 
                   
               
               
                   
                 
                   AGAGCTGCCTCACTTGCAAAAATAGCTCATATGTCGCCACATGTAAAGGCTGCC 
                 
                   
               
               
                   
                 
                   CTAAGGGCATCATCCGTGTTGATCTGGGCTTATGGGGATAATGAAGTAAATTG 
                 
                   
               
               
                   
                 
                   GACTGCTGCTCTTACGATTGCAAAATCTCGGTGTAATGTAAACTTAGAGTATCT 
                 
                   
               
               
                   
                 
                   TCGGTTACTGTCCCCTTTACCCACGGCTGGGAATCTTCAACATAGACTAGATGA 
                 
                   
               
               
                   
                 
                   TGGTATAACTCAGATGACATTCACCCCTGCATCTCTCTACAGGGTGTCACCTTAC 
                 
                   
               
               
                   
                 
                   ATTCACATATCCAATGATTCTCAAAGGCTGTTCACTGAAGAAGGAGTCAAAGA 
                 
                   
               
               
                   
                 
                   GGGGAATGTGGTTTACCAACAGATCATGCTCTTGGGTTTATCTCTAATCGAATC 
                 
                   
               
               
                   
                 
                   GATCTTTCCAATGACAACAACCAGGACATATGATGAGATCACACTGCACCTACA 
                 
                   
               
               
                   
                 
                   TAGTAAATTTAGTTGCTGTATCAGAGAAGCACCTGTTGCGGTTCCTTTCGAGCT 
                 
                   
               
               
                   
                 
                   ACTTGGGGTGGTACCGGAACTGAGGACAGTGACCTCAAATAAGTTTATGTATG 
                 
                   
               
               
                   
                 
                   ATCCTAGCCCTGTATCGGAGGGAGACTTTGCGAGACTTGACTTAGCTATCTTCA 
                 
                   
               
               
                   
                 
                   AGAGTTATGAGCTTAATCTGGAGTCATATCCCACGATAGAGCTAATGAACATT 
                 
                   
               
               
                   
                 
                   CTTTCAATATCCAGCGGGAAGTTGATTGGCCAGTCTGTGGTTTCTTATGATGAA 
                 
                   
               
               
                   
                 
                   GATACCTCCATAAAGAATGACGCCATAATAGTGTATGACAATACCCGAAATTG 
                 
                   
               
               
                   
                 
                   GATCAGTGAAGCTCAGAATTCAGATGTGGTCCGCCTATTTGAATATGCAGCACT 
                 
                   
               
               
                   
                 
                   TGAAGTGCTCCTCGACTGTTCTTACCAACTCTATTACCTGAGAGTAAGAGGCCT 
                 
                   
               
               
                   
                 
                   GGACAATATTGTCTTATATATGGGTGATTTATACAAGAATATGCCAGGAATTCT 
                 
                   
               
               
                   
                 
                   ACTTTCCAACATTGCAGCTACAATATCTCATCCCGTCATTCATTCAAGGTTACAT 
                 
                   
               
               
                   
                 
                   GCAGTGGGCCTGGTCAACCATGACGGATCACACCAACTTGCAGATACGGATTT 
                 
                   
               
               
                   
                 
                   TATCGAAATGTCTGCAAAACTATTAGTATCTTGCACCCGACGTGTGATCTCCGG 
                 
                   
               
               
                   
                 
                   CTTATATTCAGGAAATAAGTATGATCTGCTGTTCCCATCTGTCTTAGATGATAA 
                 
                   
               
               
                   
                 
                   CCTGAATGAGAAGATGCTTCAGCTGATATCCCGGTTATGCTGTCTGTACACGGT 
                 
                   
               
               
                   
                 
                   ACTCTTTGCTACAACAAGAGAAATCCCGAAAATAAGAGGCTTAACTGCAGAAG 
                 
                   
               
               
                   
                 
                   AGAAATGTTCAATACTCACTGAGTATTTACTGTCGGATGCTGTGAAACCATTAC 
                 
                   
               
               
                   
                 
                   TTAGCCCCGATCAAGTGAGCTCTATCATGTCTCCTAACATAATTACATTCCCAGC 
                 
                   
               
               
                   
                 
                   TAATCTGTACTACATGTCTCGGAAGAGCCTCAATTTGATCAGGGAAAGGGAGG 
                 
                   
               
               
                   
                 
                   ACAGGGATACTATCCTGGCGTTGTTGTTCCCCCAAGAGCCATTATTAGAGTTCC 
                 
                   
               
               
                   
                 
                   CTTCTGTGCAAGATATTGGTGCTCGAGTGAAAGATCCATTCACCCGACAACCTG 
                 
                   
               
               
                   
                 
                   CGGCATTTTTGCAAGAGTTAGATTTGAGTGCTCCAGCAAGGTATGACGCATTCA 
                 
                   
               
               
                   
                 
                   CACTTAGTCAGATTCATCCTGAACTCACATCTCCAAATCCGGAGGAAGACTACT 
                 
                   
               
               
                   
                 
                   TAGTACGATACTTGTTCAGAGGGATAGGGACTGCATCTTCCTCTTGGTATAAGG 
                 
                   
               
               
                   
                 
                   CATCTCATCTCCTTTCTGTACCCGAGGTAAGATGTGCAAGACACGGGAACTCCT 
                 
                   
               
               
                   
                 
                   TATACTTAGCTGAAGGGAGCGGAGCCATCATGAGTCTTCTCGAACTGCATGTA 
                 
                   
               
               
                   
                 
                   CCACATGAAACTATCTATTACAATACGCTCTTTTCAAATGAGATGAACCCCCCG 
                 
                   
               
               
                   
                 
                   CAACGACATTTCGGGCCGACCCCAACTCAGTTTTTGAATTCGGTTGTTTATAGG 
                 
                   
               
               
                   
                 
                   AATCTACAGGCGGAGGTAACATGCAAAGATGGATTTGTCCAAGAGTTCCGTCC 
                 
                   
               
               
                   
                 
                   ATTATGGAGAGAAAATACAGAGGAAAGCGACCTGACCTCAGATAAAGTAGTG 
                 
                   
               
               
                   
                 
                   GGGTATATTACATCTGCAGTGCCCTACAGATCTGTATCATTGCTGCATTGTGAC 
                 
                   
               
               
                   
                 
                   ATTGAAATTCCTCCAGGGTCCAATCAAAGCTTACTAGATCAACTAGCTATCAAT 
                 
                   
               
               
                   
                 
                   TTATCTCTGATTGCCATGCATTCTGTAAGGGAGGGCGGGGTAGTAATCATCAA 
                 
                   
               
               
                   
                 
                   AGTGTTGTATGCAATGGGATACTACTTTCATCTACTCATGAACTTGTTTGCTCCG 
                 
                   
               
               
                   
                 
                   TGTTCCACAAAAGGATATATTCTCTCTAATGGTTATGCATGTCGAGGAGATATG 
                 
                   
               
               
                   
                 
                   GAGTGTTACCTGGTATTTGTCATGGGTTACCTGGGCGGGCCTACATTTGTACAT 
                 
                   
               
               
                   
                 
                   GAGGTGGTGAGGATGGCGAAAACTCTGGTGCAGCGGCACGGTACGCTTTTGT 
                 
                   
               
               
                   
                 
                   CTAAATCAGATGAGATCACACTGACCAGGTTATTCACCTCACAGCGGCAGCGT 
                 
                   
               
               
                   
                 
                   GTGACAGACATCCTATCCAGTCCTTTACCAAGATTAATAAAGTACTTGAGGAA 
                 
                   
               
               
                   
                 
                   GAATATTGACACTGCGCTGATTGAAGCCGGGGGACAGCCCGTCCGTCCATTCT 
                 
                   
               
               
                   
                 
                   GTGCGGAGAGTCTGGTGAGCACGCTAGCGAACATAACTCAGATAACCCAGATC 
                 
                   
               
               
                   
                 
                   ATCGCTAGTCACATTGACACAGTTATCCGGTCTGTGATATATATGGAAGCTGAG 
                 
                   
               
               
                   
                 
                   GGTGATCTCGCTGACACAGTATTTCTATTTACCCCTTACAATCTCTCTACTGACG 
                 
                   
               
               
                   
                 
                   GGAAAAAGAGGACATCACTTAAACAGTGCACGAGACAGATCCTAGAGGTTAC 
                 
                   
               
               
                   
                 
                   AATACTAGGTCTTAGAGTCGAAAATCTCAATAAAATAGGCGATATAATCAGCC 
                 
                   
               
               
                   
                 
                   TAGTGCTTAAAGGCATGATCTCCATGGAGGACCTTATCCCACTAAGGACATACT 
                 
                   
               
               
                   
                 
                   TGAAGCATAGTACCTGCCCTAAATATTTGAAGGCTGTCCTAGGTATTACCAAAC 
                 
                   
               
               
                   
                 
                   TCAAAGAAATGTTTACAGACACTTCTGTACTGTACTTGACTCGTGCTCAACAAA 
                 
                   
               
               
                   
                 
                   AATTCTACATGAAAACTATAGGCAATGCAGTCAAAGGATATTACAGTAACTGT 
                 
                   
               
               
                   
                 
                   GACTCTTAACGAAAATCACATATTAATAGGCTCCTTTTTTGGCCAATTGTATTCT 
                 
                   
               
               
                   
                 
                   TGTTGATTTAATCATATTATGTTAGAAAAAAGTTGAACCCTGACTCCTTAGGAC 
                 
                   
               
               
                   
                 
                   TCGAATTCGAACTCAAATAAATGTCTTAAAAAAAGGTTGCGCACAATTATTCTT 
                 
                   
               
               
                   
                   GAGTGTAGTCTCGTCATTCACCAAATCTTTGTTTGGT GCGCGCGGCCGGCATGG 
                   
               
               
                   
                 TCCCAGCCTCCTCGCTGGCGCCGGCTGGGCAACATTCCGAGGGGACCGTCCCCT 
                   
               
               
                   
                 CGGTAATGGCGAATGGGACGTCGACTGCTAACAAAGCCCGAAAGGAAGCTGAG 
                   
               
               
                   
                 TTGGCTGCTGCCACCGCTGAGCAATAACTAGCATAACCCCTTGGGGCCTCTAAAC 
                   
               
               
                   
                 GGGTCTTGAGGGGTTTTTTGCTGAAAGGAGGAACTATATGCGCGCAGATCTGTC 
                   
               
               
                   
                 ATGATGATCATTGCAATTGGATCCATATATAGGGCCCGGGTTATAATTACCTCAG 
                   
               
               
                   
                 GTCGACGTCCCATGGCCATTCGAATTCGTAATCATGGTCATAGCTGTTTCCTGTG 
                   
               
               
                   
                 TGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGT 
                   
               
               
                   
                 GTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCT 
                   
               
               
                   
                 CACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGG 
                   
               
               
                   
                 CCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGC 
                   
               
               
                 Additional 
                   GTCGAC ATTTTTAATTAAAATAGGGTGGGGAAGGTACCGCCACC ATGCACCTGC   
                 89 
               
               
                 transcription 
                 
                   TGTGCTTCCTGAGCCTGGCCTGCAGCCTGCTGGCCGCCGCCCTGATCCCCAGCC 
                 
                   
               
               
                 unit 
                 
                   CCAGAGAGGCCCCCGCCACCGTGGCCGCCTTCGAGAGCGGCCTGGGCTTCAGC 
                 
                   
               
               
                 encoding 
                 
                   GAGGCCGAGCCCGACGGCGGCGAGGTGAAGGCCTTCGAGGGCAAGGACCTG 
                 
                   
               
               
                 codon 
                 
                   GAGGAGCAGCTGAGAAGCGTGAGCAGCGTGGACGAGCTGATGAGCGTGCTG 
                 
                   
               
               
                 optimized 
                 
                   TACCCCGACTACTGGAAGATGTACAAGTGCCAGCTGAGAAAGGGCGGCTGGC 
                 
                   
               
               
                 mVEGF-C 
                 
                   AGCAGCCCACCCTGAACACCAGAACCGGCGACAGCGTGAAGTTCGCCGCCGCC 
                 
                   
               
               
                 with APMV 
                 
                   CACTACAACACCGAGATCCTGAAGAGCATCGACAACGAGTGGAGAAAGACCC 
                 
                   
               
               
                 gene end, 
                 
                   AGTGCATGCCCAGAGAGGTGTGCATCGACGTGGGCAAGGAGTTCGGCGCCGC 
                 
                   
               
               
                 intergenic 
                 
                   CACCAACACCTTCTTCAAGCCCCCCTGCGTGAGCGTGTACAGATGCGGCGGCTG 
                 
                   
               
               
                 and gene 
                 
                   CTGCAACAGCGAGGGCCTGCAGTGCATGAACACCAGCACCGGCTACCTGAGCA 
                 
                   
               
               
                 start 
                 
                   AGACCCTGTTCGAGATCACCGTGCCCCTGAGCCAGGGCCCCAAGCCCGTGACC 
                 
                   
               
               
                 sequences 
                 
                   ATCAGCTTCGCCAACCACACCAGCTGCAGATGCATGAGCAAGCTGGACGTGTA 
                 
                   
               
               
                 and Kozak 
                 
                   CAGACAGGTGCACAGCATCATCAGAAGAAGCCTGCCCGCCACCCTGCCCCAGT 
                 
                   
               
               
                 sequence, 
                 
                   GCCAGGCCGCCAACAAGACCTGCCCCACCAACTACGTGTGGAACAACTACATG 
                 
                   
               
               
                 (size =1302 
                 
                   TGCAGATGCCTGGCCCAGCAGGACTTCATCTTCTACAGCAACGTGGAGGACGA 
                 
                   
               
               
                 nt, rule of 6 
                 
                   CAGCACCAACGGCTTCCACGACGTGTGCGGCCCCAACAAGGAGCTGGACGAG 
                 
                   
               
               
                 OK). 
                 
                   GACACCTGCCAGTGCGTGTGCAAGGGCGGCCTGAGACCCAGCAGCTGCGGCCC 
                 
                   
               
               
                 Flanking Sal 
                 
                   CCACAAGGAGCTGGACAGAGACAGCTGCCAGTGCGTGTGCAAGAACAAGCTG 
                 
                   
               
               
                 I sites 
                 
                   TTCCCCAACAGCTGCGGCGCCAACAGAGAGTTCGACGAGAACACCTGCCAGTG 
                 
                   
               
               
                 underlined. 
                 
                   CGTGTGCAAGAGAACCTGCCCCAGAAACCAGCCCCTGAACCCCGGCAAGTGCG 
                 
                   
               
               
                 Open reading 
                 
                   CCTGCGAGTGCACCGAGAACACCCAGAAGTGCTTCCTGAAGGGCAAGAAGTTC 
                 
                   
               
               
                 frame in 
                 
                   CACCACCAGACCTGCAGCTGCTACAGAAGACCCTGCGCCAACAGACTGAAGCA 
                 
                   
               
               
                 bold. 
                 
                   CTGCGACCCCGGCCTGAGCTTCAGCGAGGAGGTGTGCAGATGCGTGCCCAGCT 
                 
                   
               
               
                   
                   ACTGGAAGAGACCCCACCTGAACTGA CCGG GTCGAC   
                   
               
               
                 pRz- 
                 TCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCG 
                 90 
               
               
                 APMV4- 
                 AGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGG 
                   
               
               
                 mVEGF-C 
                 ATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGT 
                   
               
               
                 Rescue 
                 AAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCA 
                   
               
               
                 plasmid 
                 TCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAA 
                   
               
               
                 containing 
                 GATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACC 
                   
               
               
                 the full- 
                 CTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCT 
                   
               
               
                 length cDNA 
                 TTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAA 
                   
               
               
                 of APMV4 
                 GCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCC 
                   
               
               
                 with an 
                 GGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGC 
                   
               
               
                 additional 
                 AGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACA 
                   
               
               
                 transcription 
                 GAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAACAGTATTTGGT 
                   
               
               
                 unit 
                 ATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGA 
                   
               
               
                 encoding a 
                 TCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCA 
                   
               
               
                 codon- 
                 GATTACGCGCAGAAAAAAACGATCTCAAGAAGATCCTTTGATCTTTTCTACGGG 
                   
               
               
                 optimized 
                 GTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATT 
                   
               
               
                 mVEGF-C. 
                 ATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAA 
                   
               
               
                 (Additional 
                 TCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGA 
                   
               
               
                 transcription 
                 GGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCC 
                   
               
               
                 unit in bold.) 
                 CGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTG 
                   
               
               
                   
                 CAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAAC 
                   
               
               
                   
                 CAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCT 
                   
               
               
                   
                 CCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTA 
                   
               
               
                   
                 ATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCG 
                   
               
               
                   
                 TCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACA 
                   
               
               
                   
                 TGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTT 
                   
               
               
                   
                 GTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCA 
                   
               
               
                   
                 TAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTAC 
                   
               
               
                   
                 TCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCC 
                   
               
               
                   
                 GGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCA 
                   
               
               
                   
                 TCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGA 
                   
               
               
                   
                 GATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTA 
                   
               
               
                   
                 CTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAA 
                   
               
               
                   
                 AAGGGAATAAGGGCGACACGGAAATGTTGAATACTCATACTCTTCCTTTTTCAA 
                   
               
               
                   
                 TATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAAT 
                   
               
               
                   
                 GTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGC 
                   
               
               
                   
                 CACCTGACGTCTAAGAAACCATTATTATCATGACATTAACCTATAAAAATAGGCG 
                   
               
               
                   
                 TATCACGAGGCCCTTTCGTCTCGCGCGTTTCGGTGATGACGGTGAAAACCTCT 
                   
               
               
                   
                 GACACATGCAGCTCCCGGAGACGGTCACAGCTTGTCTGTAAGCGGATGCCGG 
                   
               
               
                   
                 GAGCAGACAAGCCCGTCAGGGCGCGTCAGCGGGTGTTGGCGGGTGTCGGGG 
                   
               
               
                   
                 CTGGCTTAACTATGCGGCATCAGAGCAGATTGTACTGAGAGTGCACCATAAAAT 
                   
               
               
                   
                 TGTAAACGTTAATATTTTGTTAAAATTCGCGTTAAATTTTTGTTAAATCAGCTCAT 
                   
               
               
                   
                 TTTTTAACCAATAGGCCGAAATCGGCAAAATCCCTTATAAATCAAAAGAATAGCC 
                   
               
               
                   
                 CGAGATAGGGTTGAGTGTTGTTCCAGTTTGGAACAAGAGTCCACTATTAAAGAA 
                   
               
               
                   
                 CGTGGACTCCAACGTCAAAGGGCGAAAAACCGTCTATCAGGGCGATGGCCCA 
                   
               
               
                   
                 CTACGTGAACCATCACCCAAATCAAGTTTTTTGGGGTCGAGGTGCCGTAAAGC 
                   
               
               
                   
                 ACTAAATCGGAACCCTAAAGGGAGCCCCCGATTTAGAGCTTGACGGGGAAAGC 
                   
               
               
                   
                 CGGCGAACGTGGCGAGAAAGGAAGGGAAGAAAGCGAAAGGAGCGGGCGCTA 
                   
               
               
                   
                 GGGCGCTGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCACACCCGCCGC 
                   
               
               
                   
                 GCTTAATGCGCCGCTACAGGGCGCGTACTATGGTTGCTTTGACGTATGCGGTG 
                   
               
               
                   
                 TGAAATACCGCACAGATGCGTAAGGAGAAAATACCGCATCAGGCGCCATTCGC 
                   
               
               
                   
                 CATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCGGTGCGGGCCTCTTCGCT 
                   
               
               
                   
                 ATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAA 
                   
               
               
                   
                 CGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGCCAAGCTT 
                   
               
               
                   
                 TAATACGACTCACTATAGGGAGATTGGTCTGATGAGTCCGTGAGGACGAAACG 
                   
               
               
                   
                 GAGTCTAGACTCCGTCACGAAAAAGAAGAATAAAAGGCAGAAGCCTTTTAAAAG 
                   
               
               
                   
                 GAACCCTGGGCTGTCGTAGGTGTGGGAAGGTTGTATTCCGAGTGCGCCTCCG 
                   
               
               
                   
                 AGGCATCTACTCTACACCTATCACAATGGCTGGTGTCTTCTCCCAGTATGAGAG 
                   
               
               
                   
                 GTTTGTGGACAATCAATCCCAAGTGTCAAGGAAGGATCATCGGTCCTTAGCAG 
                   
               
               
                   
                 GAGGATGCCTTAAAGTTAACATCCCTATGCTTGTCACTGCATCTGAAGACCCCA 
                   
               
               
                   
                 CCACTCGTTGGCAACTAGCATGCTTATCTCTAAGGCTCCTGATCTCCAACTCAT 
                   
               
               
                   
                 CAACCAGTGCTATCCGTCAGGGGGCAATACTGACTCTCATGTCATTACCATCAC 
                   
               
               
                   
                 AAAACATGAGAGCAACAGCAGCTATTGCTGGTTCCACAAATGCAGCTGTTATCA 
                   
               
               
                   
                 ACACCATGGAAGTCTTAAGTGTCAACGACTGGACCCCATCCTTCGACCCTAGG 
                   
               
               
                   
                 AGCGGTCTTTCTGAGGAAGATGCTCAAGTTTTCAGAGACATGGCAAGAGATCT 
                   
               
               
                   
                 GCCCCCTCAGTTCACCTCTGGATCACCCTTCACATCAGCATTGGCGGAGGGGT 
                   
               
               
                   
                 TCACTCCTGAAGATACTCATGACCTGATGGAGGCCTTGACCAGTGTGCTGATA 
                   
               
               
                   
                 CAGATCTGGATCCTGGTGGCTAAGGCCATGACCAACATTGACGGCTCTGGGGA 
                   
               
               
                   
                 GGCCAATGAAAGACGTCTTGCAAAGTACATCCAAAAAGGACAGCTTAATCGTCA 
                   
               
               
                   
                 GTTTGCAATTGGTAATCCTGCCCGTCTGATAATCCAACAGACAATCAAAAGCTC 
                   
               
               
                   
                 CTTAACTGTCCGTAGGTTCTTGGTCTCTGAGCTTCGTGCGTCACGAGGTGCAG 
                   
               
               
                   
                 TAAAAGAAGGATCCCCTTACTATGCAGCTGTTGGGGATATCCACGCTTACATCT 
                   
               
               
                   
                 TTAATGCGGGATTGACACCATTCTTGACCACCTTAAGATACGGGATAGGCACCA 
                   
               
               
                   
                 AGTACGCCGCTGTTGCACTCAGTGTGTTCGCTGCAGATATTGCAAAGTTGAAG 
                   
               
               
                   
                 AGCCTACTTACCCTGTACCAGGACAAGGGTGTAGAAGCTGGATACATGGCACT 
                   
               
               
                   
                 CCTTGAGGATCCAGACTCCATGCACTTTGCACCTGGAAACTTCCCACACATGTA 
                   
               
               
                   
                 CTCCTATGCAATGGGGGTAGCTTCTTACCATGATCCTAGCATGCGCCAATACCA 
                   
               
               
                   
                 ATACGCCAGGAGGTTCCTCAGCCGTCCTTTCTACTTACTAGGAAGGGACATGG 
                   
               
               
                   
                 CCGCCAAGAACACAGGCACGCTGGATGAGCAACTGGCGAAGGAACTGCAAGT 
                   
               
               
                   
                 ATCAGAGAGAGATCGCGCCGCATTATCCGCTGCGATTCAATCAGCGATGGAGG 
                   
               
               
                   
                 GGGGAGAGTCCGACGACTTCCCACTGTCGGGATCCATGCCGGCTCTCTCTGA 
                   
               
               
                   
                 GAATGCGCAACCAGTTACCCCCAGACCTCAACAGTCCCAGCTCTCTCCCCCCC 
                   
               
               
                   
                 AATCATCAAACATGCCCCAATCAGCACCCAGGACCCCAGACTATCAACCCGAC 
                   
               
               
                   
                 TTTGAACTGTAGGCTTCATCACCGCACCAACAACAGCCCAAGAAGACCACCCC 
                   
               
               
                   
                 TCCCCCCACACATCTCACCCAGCCACCCATAAAGACTCAGTGGCGCGCCCCAG 
                   
               
               
                   
                 CATCTCCTTCATTTAATTAAAAACCGACCAACAGGGTGGGGAAGGAGAGTCATT 
                   
               
               
                   
                 GGCTACTGCCAATTGTGTGCAGCAATGGATTTTACTGACATTGATGCTGTCAAC 
                   
               
               
                   
                 TCATTGATCGAATCATCATCGGCAATCATAGACTCCATACAGCATGGAGGGCTG 
                   
               
               
                   
                 CAACCAGCGGGCACCGTCGGCCTATCGCAGATCCCAAAAGGGATAACCAGCG 
                   
               
               
                   
                 CATTAACCAAGGCCTGGGAGGCTGAGGCGGCAACTGCCGGTAATGGGGACAC 
                   
               
               
                   
                 CCAACACAAATCTGACAGTCCGGAGGATCATCAGGCCAACGACACAGATTCCC 
                   
               
               
                   
                 CTGAAGACACAGGTACTGACCAGACCACCCAGGAGGCCAACATCGTTGAGACA 
                   
               
               
                   
                 CCCCACCCCGAGGTGCTGTCAGCAGCCAAAGCCAGACTCAAGAGGCCCAAAG 
                   
               
               
                   
                 CAGGGAGGGACACCCGCGACAACTCCCCTGCGCAACCCGATCATCTTTTAAG 
                   
               
               
                   
                 GGGGGCCTCCTGAGCCCACAACCAGCAGCATCATGGGTGCAAAATCCACCCA 
                   
               
               
                   
                 GTCATGGAGGTCCCGGCACCGCCGATCCCCGCCCATCACAAACTCAGGATCAT 
                   
               
               
                   
                 TCCCCCACCGGAGAGAAATGGCGATTGTCACCGACAAAGCAACCGGAGACATT 
                   
               
               
                   
                 GAACTGGTGGAGTGGTGCAACCCGGGGTGCACAGCAGTCCGAATTGAACCCA 
                   
               
               
                   
                 CCAGACTCGACTGTGTATGCGGACACTGCCCCACCATCTGTAGCCTCTGCATG 
                   
               
               
                   
                 TATGACGACTGATCAGGTACAACTACTAATGAAGGAGGTTGCTGACATAAAATC 
                   
               
               
                   
                 ACTCCTTCAGGCGTTAGTGAGGAACCTCGCTGTCTTGCCCCAATTGAGGAATG 
                   
               
               
                   
                 AGGTTGCAGCAATCAGAACATCACAGGCCATGATAGAGGGGACACTCAATTCG 
                   
               
               
                   
                 ATCAAGATTCTTGACCCTGGGAATTATCAGGAATCATCACTAAACAGTTGGTTC 
                   
               
               
                   
                 AAACCTCGCCAAGATCACACTGTTGTTGTGTCTGGACCAGGGAATCCATTGGC 
                   
               
               
                   
                 CATGCCAACCCCAGTCCAAGACAACACCATATTCCTGGACGAGCTAGCCAGAC 
                   
               
               
                   
                 CTCATCCTAGTGTGGTCAATCCATCCCCGCCCATCACCAACACCAATGTTGACC 
                   
               
               
                   
                 TTGGCCCACAGAAGCAGGCTGCAATAGCCTATATCTCCGCTAAATGCAAGGAT 
                   
               
               
                   
                 CCGGGGAAACGAGATCAGCTATCAAGGCTCATTGAGCGAGCAACCACCCCAA 
                   
               
               
                   
                 GTGAGATCAACAAAGTTAAAAGACAAGCCCTTGGGCTCTAGATCACTCGATCAC 
                   
               
               
                   
                 CCCTCATGGTGATCACAACAATAATCAGAACCCTTCCGAACCACATGACCAACC 
                   
               
               
                   
                 CAGCCCACCGCCCACACCGTCC GTCGACATTTTTAATTAAAATAGGGTGGGG   
                   
               
               
                   
                 
                   AAGGTACCGCCACCATGCACCTGCTGTGCTTCCTGAGCCTGGCCTGCAGCCT 
                 
                   
               
               
                   
                 
                   GCTGGCCGCCGCCCTGATCCCCAGCCCCAGAGAGGCCCCCGCCACCGTGGC 
                 
                   
               
               
                   
                 
                   CGCCTTCGAGAGCGGCCTGGGCTTCAGCGAGGCCGAGCCCGACGGCGGCG 
                 
                   
               
               
                   
                 
                   AGGTGAAGGCCTTCGAGGGCAAGGACCTGGAGGAGCAGCTGAGAAGCGTGA 
                 
                   
               
               
                   
                 
                   GCAGCGTGGACGAGCTGATGAGCGTGCTGTACCCCGACTACTGGAAGATGT 
                 
                   
               
               
                   
                 
                   ACAAGTGCCAGCTGAGAAAGGGCGGCTGGCAGCAGCCCACCCTGAACACCA 
                 
                   
               
               
                   
                 
                   GAACCGGCGACAGCGTGAAGTTCGCCGCCGCCCACTACAACACCGAGATCC 
                 
                   
               
               
                   
                 
                   TGAAGAGCATCGACAACGAGTGGAGAAAGACCCAGTGCATGCCCAGAGAGG 
                 
                   
               
               
                   
                 
                   TGTGCATCGACGTGGGCAAGGAGTTCGGCGCCGCCACCAACACCTTCTTCAA 
                 
                   
               
               
                   
                 
                   GCCCCCCTGCGTGAGCGTGTACAGATGCGGCGGCTGCTGCAACAGCGAGGG 
                 
                   
               
               
                   
                 
                   CCTGCAGTGCATGAACACCAGCACCGGCTACCTGAGCAAGACCCTGTTCGAG 
                 
                   
               
               
                   
                 
                   ATCACCGTGCCCCTGAGCCAGGGCCCCAAGCCCGTGACCATCAGCTTCGCC 
                 
                   
               
               
                   
                 
                   AACCACACCAGCTGCAGATGCATGAGCAAGCTGGACGTGTACAGACAGGTG 
                 
                   
               
               
                   
                 
                   CACAGCATCATCAGAAGAAGCCTGCCCGCCACCCTGCCCCAGTGCCAGGCC 
                 
                   
               
               
                   
                 
                   GCCAACAAGACCTGCCCCACCAACTACGTGTGGAACAACTACATGTGCAGAT 
                 
                   
               
               
                   
                 
                   GCCTGGCCCAGCAGGACTTCATCTTCTACAGCAACGTGGAGGACGACAGCA 
                 
                   
               
               
                   
                 
                   CCAACGGCTTCCACGACGTGTGCGGCCCCAACAAGGAGCTGGACGAGGACA 
                 
                   
               
               
                   
                 
                   CCTGCCAGTGCGTGTGCAAGGGCGGCCTGAGACCCAGCAGCTGCGGCCCCC 
                 
                   
               
               
                   
                 
                   ACAAGGAGCTGGACAGAGACAGCTGCCAGTGCGTGTGCAAGAACAAGCTGT 
                 
                   
               
               
                   
                 
                   TCCCCAACAGCTGCGGCGCCAACAGAGAGTTCGACGAGAACACCTGCCAGT 
                 
                   
               
               
                   
                 
                   GCGTGTGCAAGAGAACCTGCCCCAGAAACCAGCCCCTGAACCCCGGCAAGT 
                 
                   
               
               
                   
                 
                   GCGCCTGCGAGTGCACCGAGAACACCCAGAAGTGCTTCCTGAAGGGCAAGA 
                 
                   
               
               
                   
                 
                   AGTTCCACCACCAGACCTGCAGCTGCTACAGAAGACCCTGCGCCAACAGACT 
                 
                   
               
               
                   
                 
                   GAAGCACTGCGACCCCGGCCTGAGCTTCAGCGAGGAGGTGTGCAGATGCGT 
                 
                   
               
               
                   
                   GCCCAGCTACTGGAAGAGACCCCACCTGAACTGACCGGGTCGAC ATCCCTTG 
                   
               
               
                   
                 CCAAACATCCTGCCGTAGCTGATTTATTCAAAAGAGCTCATTTGATATGACCTG 
                   
               
               
                   
                 GTAATCATAAAATAGGGTGGGGAAGGTGCTTTGCCTGTAAGGGGGCTCCCTCA 
                   
               
               
                   
                 TCTTCAGACACGTGCCCGCCATCTCACCAACAGTGCAATGGCAGACATGGACA 
                   
               
               
                   
                 CGGTGTATATCAATCTGATGGCAGATGACCCAACCCACCAAAAAGAACTGCTGT 
                   
               
               
                   
                 CCTTTCCTCTCATCCCTGTGACCGGTCCTGACGGGAAGAAGGAACTCCAACAC 
                   
               
               
                   
                 CAGATCCGGACCCAATCCTTGCTCGCCTCAGACAAACAAACTGAACGGTTCAT 
                   
               
               
                   
                 CTTCCTCAACACTTACGGATTCATCTATGACACCACACCGGACAAGACAACTTT 
                   
               
               
                   
                 TTCCACCCCAGAGCATATTAATCAGCCTAAGAGGACGACGGTGAGTGCCGCGA 
                   
               
               
                   
                 TGATGACCATTGGCCTGGTTCCCGCCAATATACCCCTGAACGAACTAACGGCT 
                   
               
               
                   
                 ACTGTGTTCAGCCTTAAAGTAAGAGTGAGGAAAAGTGCGAGGTATCGGGAAGT 
                   
               
               
                   
                 GGTCTGGTATCAATGCAATCCAGTACCGGCCCTGCTTGCAGCCACCAGGTTTG 
                   
               
               
                   
                 GTCGCCAAGGAGGTCTCGAGTCGAGCACTGGAGTCAGTGTAAAGGCTCCCGA 
                   
               
               
                   
                 GAAGATAGATTGTGAGAAGGATTATACCTACTACCCTTATTTCTTATCTGTGTGC 
                   
               
               
                   
                 TACATCGCCACCTCCAACCTGTTCAAGGTACCGAGGATGGTTGCTAATGCAAC 
                   
               
               
                   
                 CAACAGTCAATTATACCACCTTACCATGCAGGTCACATTTGCCTTTCCAAAAAAC 
                   
               
               
                   
                 ATCCCTCCAGCCAACCAGAAACTCCTGACACAGGTGGATGAGGGATTCGAGGG 
                   
               
               
                   
                 CACTGTGGATTGCCATTTTGGGAACATGCTGAAAAAGGATCGGAAAGGGAACA 
                   
               
               
                   
                 TGAGGACACTGTCCCAGGCGGCAGATAAGGTCAGACGAATGAATATTCTTGTT 
                   
               
               
                   
                 GGTATCTTTGACTTGCATGGGCCAACGCTCTTCCTGGAGTATACCGGGAAACT 
                   
               
               
                   
                 GACAAAGGCTCTGCTAGGGTTCATGTCCACCAGCCGAACAGCAATCATCCCCA 
                   
               
               
                   
                 TATCTCAGCTCAATCCCATGCTGAGTCAACTCATGTGGAGCAGTGATGCCCAG 
                   
               
               
                   
                 ATAGTAAAGTTAAGGGTTGTCATAACTACATCCAAACGCGGCCCGTGCGGGGG 
                   
               
               
                   
                 TGAGCAGGAGTATGTGCTGGATCCCAAATTCACAGTTAAGAAAGAAAAGGCTC 
                   
               
               
                   
                 GACTCAACCCTTTCAAGAAGGCAGCCTAATGATTTAATCCGCAAGATCCCAGAA 
                   
               
               
                   
                 ATCAGACCACTCTATACTATCCACTGATCACTGGAAATGTAATCCTGCAGGTGA 
                   
               
               
                   
                 TGAATCTGTGAAGAATCAATTAAAAAACCGGATCCTTATTAGGGTGGGGAAGTA 
                   
               
               
                   
                 GTTGATTGGGTGTCTAAACAAAAGCATTTCTTCACACCTCCCCGCCACGAAACA 
                   
               
               
                   
                 ACCACAATGAGGCTATCAAACACAATCTTGACCTTGATTCTCATCATACTTACCG 
                   
               
               
                   
                 GCTATTTGATAGGTGTCCACTCCACCGATGTGAATGAGAAACCAAAGTCCGAA 
                   
               
               
                   
                 GGGATTAGGGGTGATCTTACACCAGGTGCGGGTATTTTCGTAACTCAAGTCCG 
                   
               
               
                   
                 ACAGCTCCAGATCTACCAACAGTCTGGGTACCATGATCTTGTCATCAGATTGTT 
                   
               
               
                   
                 ACCTCTTCTACCAACAGAGCTTAATGATTGTCAAAGGGAAGTTGTCACAGAGTA 
                   
               
               
                   
                 CAATAACACTGTATCACAGCTGTTGCAGCCTATCAAAACCAACCTGGATACTTT 
                   
               
               
                   
                 GTTGGCAGATGGTAGCACAAGGGATGTTGATATACAGCCGCGATTCATTGGGG 
                   
               
               
                   
                 CAATAATAGCCACAGGTGCCCTGGCTGTAGCAACGGTAGCTGAGGTAACTGCA 
                   
               
               
                   
                 GCTCAAGCACTATCTCAGTCAAAAACGAATGCTCAAAATATTCTCAAGTTGAGA 
                   
               
               
                   
                 GATAGTATTCAGGCCACCAACCAAGCAGTTTTTGAAATTTCACAGGGACTCGAA 
                   
               
               
                   
                 GCAACTGCAACCGTGCTATCAAAACTGCAAACTGAGCTCAATGAGAATATCATC 
                   
               
               
                   
                 CCAAGTCTGAACAACTTGTCCTGTGCTGCCATGGGGAATCGCCTTGGTGTATC 
                   
               
               
                   
                 ACTCTCACTCTATTTGACCTTAATGACCACTCTATTTGGGGACCAGATCACAAA 
                   
               
               
                   
                 CCCAGTGCTGACGCCAATCTCTTACAGCACCCTATCGGCAATGGCGGGTGGTC 
                   
               
               
                   
                 ACATTGGTCCAGTGATGAGTAAGATATTAGCCGGATCTGTCACAAGTCAGTTGG 
                   
               
               
                   
                 GGGCAGAACAACTGATTGCTAGTGGCTTAATACAGTCACAGGTAGTAGGTTAT 
                   
               
               
                   
                 GATTCCCAGTATCAGCTGTTGGTTATCAGGGTCAACCTTGTACGGATTCAGGAA 
                   
               
               
                   
                 GTCCAGAATACTAGGGTTGTATCACTAAGAACACTAGCAGTCAATAGGGATGGT 
                   
               
               
                   
                 GGACTTTACAGAGCCCAGGTGCCACCCGAGGTAGTTGAGCGATCTGGCATTGC 
                   
               
               
                   
                 AGAGCGGTTTTATGCAGATGATTGTGTTCTAACTACAACTGATTACATCTGCTCA 
                   
               
               
                   
                 TCGATCCGATCTTCTCGGCTTAATCCAGAGTTAGTCAAGTGTCTCAGTGGGGCA 
                   
               
               
                   
                 CTTGATTCATGCACATTTGAGAGGGAAAGTGCATTACTGTCAACTCCCTTCTTT 
                   
               
               
                   
                 GTATACAACAAGGCAGTCGTCGCAAATTGTAAAGCAGCGACATGTAGATGTAAT 
                   
               
               
                   
                 AAACCGCCATCTATCATTGCCCAATACTCTGCATCAGCTCTAGTAACCATCACC 
                   
               
               
                   
                 ACCGACACTTGTGCTGACCTTGAAATTGAGGGTTATCGTTTCAACATACAGACT 
                   
               
               
                   
                 GAATCCAACTCATGGGTTGCACCAAACTTCACGGTCTCAACCTCACAAATAGTA 
                   
               
               
                   
                 TCGGTTGATCCAATAGACATATCCTCTGACATTGCCAAAATTAACAATTCTATCG 
                   
               
               
                   
                 AGGCTGCGCGAGAGCAGCTGGAACTGAGCAACCAGATCCTTTCCCGAATCAAC 
                   
               
               
                   
                 CCACGGATTGTGAACGACGAATCACTAATAGCTATTATCGTGACAATTGTTGTG 
                   
               
               
                   
                 CTTAGTCTCCTTGTAATTGGTCTTATTATTGTTCTCGGTGTGATGTACAAGAATC 
                   
               
               
                   
                 TTAAGAAAGTCCAACGAGCTCAAGCTGCTATGATGATGCAGCAAATGAGCTCAT 
                   
               
               
                   
                 CACAGCCTGTGACCACCAAATTGGGGACACCCTTCTAGGTGAATAATCATATCA 
                   
               
               
                   
                 ATCCATTCAATAATGAGCGGGACATACCAATCACCAACGACTGTGTCACAAGGC 
                   
               
               
                   
                 CGGTTAGGAATGCACCGGATCTCTCTCCTTCCTTTTTAATTAAAAACGATCGAA 
                   
               
               
                   
                 CTGAGGGTGAGGGGGGGGGTGTGCATGGTAGGGTGGGGAAGGTAGCCAATT 
                   
               
               
                   
                 CCTGCCCATTGGGCCGACCGTACCAAGAGAAGTCAACAGAAGTATAGATGCAG 
                   
               
               
                   
                 GGCGACATGGAGGGTAGCCGTGATAACCTCACAGTAGATGATGAATTAAAGAC 
                   
               
               
                   
                 AACATGGAGGTTAGCTTATAGAGTTGTATCCCTCCTATTGATGGTGAGTGCCTT 
                   
               
               
                   
                 GATAATCTCTATAGTAATCCTGACGAGAGATAACAGCCAAAGCATAATCACGGC 
                   
               
               
                   
                 GATCAACCAGTCGTATGACGCAGACTCAAAGTGGCAAACAGGGATAGAAGGGA 
                   
               
               
                   
                 AAATCACCTCAATCATGACTGATACGCTCGATACCAGGAATGCAGCTCTTCTCC 
                   
               
               
                   
                 ACATTCCACTCCAGCTCAATACACTTGAGGCAAACCTGTTGTCCGCCCTCGGA 
                   
               
               
                   
                 GGTAACACGGGAATTGGCCCCGGAGATCTAGAGCACTGTCGTTATCCGGTTCA 
                   
               
               
                   
                 TGACTCCGCTTACCTGCATGGAGTCAATCGATTACTCATCAATCAAACAGCTGA 
                   
               
               
                   
                 CTACACAGCAGAAGGCCCCCTGGATCATGTGAACTTCATTCCGGCACCAGTTA 
                   
               
               
                   
                 CGACTACTGGATGCACAAGGATCCCATCCTTTTCTGTATCATCATCCATTTGGT 
                   
               
               
                   
                 GCTATACACACAATGTGATTGAAACAGGTTGCAATGACCACTCAGGTAGTAATC 
                   
               
               
                   
                 AATATATCAGTATGGGGGTGATTAAGAGGGCTGGCAACGGCTTACCTTACTTCT 
                   
               
               
                   
                 CAACAGTCGTGAGTAAGTATCTGACCGATGGGTTGAATAGAAAAAGCTGTTCC 
                   
               
               
                   
                 GTAGCTGCCGGATCCGGGCATTGTTACCTCCTTTGTAGCCTAGTGTCAGAGCC 
                   
               
               
                   
                 CGAACCTGATGACTATGTGTCACCAGATCCCACACCGATGAGGTTAGGGGTGC 
                   
               
               
                   
                 TAACAAGGGATGGGTCTTACACTGAACAGGTGGTACCCGAAAGAATATTTAAGA 
                   
               
               
                   
                 ACATATGGAGCGCAAACTACCCTGGGGTAGGGTCAGGTGCTATAGTAGGAAAT 
                   
               
               
                   
                 AAGGTGTTATTCCCA1111ACGGCGGAGTGAAGAATGGATCAACCCCTGAGGT 
                   
               
               
                   
                 GATGAATAGGGGAAGATATTACTACATCCAGGATCCAAATGACTATTGCCCTGA 
                   
               
               
                   
                 CCCGCTGCAAGATCAGATCTTAAGGGCAGAACAATCGTATTATCCTACTCGATT 
                   
               
               
                   
                 TGGTAGGAGGATGGTAATGCAGGGAGTCCTAACATGTCCAGTATCCAACAATT 
                   
               
               
                   
                 CAACAATAGCCAGCCAATGCCAATCTTACTATTTCAACAACTCATTAGGATTCAT 
                   
               
               
                   
                 CGGGGCGGAATCTAGGATCTATTACCTCAATGGTAACATTTACCTTTATCAAAG 
                   
               
               
                   
                 AAGCTCGAGCTGGTGGCCTCACCCCCAAATTTACCTACTTGATTCCAGGATTGC 
                   
               
               
                   
                 AAGTCCGGGTACGCAGAACATTGACTCAGGCGTTAACCTCAAGATGTTAAATGT 
                   
               
               
                   
                 TACTGTCATTACACGACCATCATCTGGCTTTTGAATAGTCAGTCAAGATGCCC 
                   
               
               
                   
                 TAATGACTGCTTATTCGGGGTTTATTCAGATGTCTGGCCTCTTAGCCTTACCTC 
                   
               
               
                   
                 AGACAGCATATTTGCATTTACAATGTACTTACAAGGGAAGACGACACGTATTGA 
                   
               
               
                   
                 CCCAGCTTGGGCGCTATTCTCCAATCATGTAATTGGGCATGAGGCTCGTTTGTT 
                   
               
               
                   
                 CAACAAGGAGGTTAGTGCTGCTTATTCTACCACCACTTGTTTTTCGGACACCAT 
                   
               
               
                   
                 CCAAAACCAGGTGTATTGTCTGAGTATACTTGAAGTCAGAAGTGAGCTCTTGGG 
                   
               
               
                   
                 GGCATTCAAGATAGTGCCATTCCTCTATCGTGTCTTATAGGCACCTGCTTGGTC 
                   
               
               
                   
                 AAGAACCCTGAGCGGCCGTAAAATTAACACTTGATCTTCCTTAAAAACACCTAT 
                   
               
               
                   
                 CTAAATTACTGTCTGAGATCCCTGATTAGTTACCCTTTCAATCAATCAATTAATTT 
                   
               
               
                   
                 TTAATTAAAAACGGAAAAATGGGCCTAGTTCCAAGGAAAGGATGGGACCCATTA 
                   
               
               
                   
                 GGGTGGGGAAGGATTACTTTGTTCCTTGACTCGCACCCACGTACACCCAATCC 
                   
               
               
                   
                 CATTCCTGTCAAGAAGGAACCCTTCCCAAACTCACCTTGCAATGTCCAATCAGG 
                   
               
               
                   
                 CAGCTGAGATTATACTACCCACCTTCCATCTGGAATCACCCTTGATCGAGAATA 
                   
               
               
                   
                 AGTGCTTCTACTACATGCAATTACTTGGTCTCGTGTTACCACATGATCACTGGA 
                   
               
               
                   
                 GATGGAGGGCATTCGTCAA1111ACAGTGGATCAAGCACACCTTAAAAATCGTA 
                   
               
               
                   
                 ATCCCCGCTTAATGGCCCACATCGATCACACTAAGGATAGACTAAGGGCTCAT 
                   
               
               
                   
                 GGTGTCTTGGGTTTCCACCAGACTCAGACAAGTGAGAGCCGTTTCCGTGTCTT 
                   
               
               
                   
                 GCTCCATCCTGAAACTTTACCTTGGCTATCAGCAATGGGAGGATGCATCAACCA 
                   
               
               
                   
                 GGTTCCCAAGGCATGGCGGAACACTCTGAAATCTATCGAGCACAGTGTGAAGC 
                   
               
               
                   
                 AGGAGGCGACTCAACTGAAGTTACTCATGGAAAAAACCTCACTAAAGCTAACAG 
                   
               
               
                   
                 GAGTATCTTACTTATTCTCCAATTGCAATCCCGGGAAAACTGCAGCGGGAACTA 
                   
               
               
                   
                 TGCCCGTACTAAGTGAGATGGCATCAGAACTCTTGTCAAATCCCATCTCCCAAT 
                   
               
               
                   
                 TCCAATCAACATGGGGGTGTGCTGCTTCAGGGTGGCACCATGTAGTCAGCATC 
                   
               
               
                   
                 ATGAGGCTCCAACAGTATCAAAGAAGGACAGGTAAGGAAGAGAAAGCAATCAC 
                   
               
               
                   
                 TGAAGTTCAGTATGGCTCGGACACCTGTCTCATTAATGCAGACTACACCGTCGT 
                   
               
               
                   
                 TTTTTCCGCACAGGACCGTGTCATAGCAGTCTTGCCTTTCGATGTTGTCCTCAT 
                   
               
               
                   
                 GATGCAAGACCTGCTTGAATCCCGACGGAATGTCTTGTTCTGTGCCCGCTTTAT 
                   
               
               
                   
                 GTATCCCAGAAGCCAACTACATGAGAGGATAAGTACAATACTGGCCCTTGGAG 
                   
               
               
                   
                 ACCAACTCGGGAGAAAAGCACCCCAAGTCCTGTATGATTTCGTAGCTACCCTC 
                   
               
               
                   
                 GAATCATTTGCATACGCTGCTGTCCAACTTCATGACAACAACCCTATCTACGGT 
                   
               
               
                   
                 GGGGCTTTCTTTGAGTTCAATATCCAAGAACTGGAAGCTATTTTGTCCCCTGCA 
                   
               
               
                   
                 CTTAATAAGGATCAAGTCAACTTCTACATAAGTCAAGTTGTCTCAGCATACAGTA 
                   
               
               
                   
                 ACCTTCCCCCATCTGAATCAGCAGAATTGCTATGCTTACTACGCCTGTGGGGTC 
                   
               
               
                   
                 ATCCCTTGCTAAACAGTCTTGATGCAGCAAAGAAAGTCAGAGAATCTATGTGTG 
                   
               
               
                   
                 CTGGGAAGGTTCTTGATTATAATGCTATTCGACTAGTTTTGTCTTTTTATCATAC 
                   
               
               
                   
                 GTTATTAATCAATGGGTATCGGAAGAAACATAAGGGTCGCTGGCCAAATGTGAA 
                   
               
               
                   
                 TCAACATTCACTACTCAACCCGATAGTGAAGCAGCTTTACTTTGATCAGGAGGA 
                   
               
               
                   
                 GATCCCACACTCTGTTGCCCTTGAGCACTATTTAGATATCTCGATGATAGAATTT 
                   
               
               
                   
                 GAGAAGACTTTGAAGTGGAACTATCTGATAGTCTAAGCATCTTTCTGAAGGAT 
                   
               
               
                   
                 AAGTCGATAGCTTTGGATAAACAAGAATGGCACAGTGGTTTTGTCTCAGAAGTG 
                   
               
               
                   
                 ACTCCAAAGCACCTACGAATGTCTCGTCATGATCGCAAGTCTACCAATAGGCTA 
                   
               
               
                   
                 TTGTTAGCCTTTATTAACTCCCCTGAATTCGATGTTAAGGAAGAGCTTAAATATT 
                   
               
               
                   
                 TGACTACAGGTGAGTATGCCACTGACCCAAATTTCAATGTCTCTTACTCACTGA 
                   
               
               
                   
                 AAGAGAAGGAAGTTAAGAAAGAAGGGCGCATTTTCGCAAAGATGTCACAGAAA 
                   
               
               
                   
                 ATGAGAGCATGCCAGGTTATTTGTGAAGAGTTACTAGCACATCATGTGGCTCCT 
                   
               
               
                   
                 TTGTTTAAAGAGAATGGTGTTACACAATCGGAGCTATCCCTGACAAAGAATTTG 
                   
               
               
                   
                 TTGGCTATTAGCCAACTGAGTTACAACTCGATGGCCGCTAAGGTGCGATTGCT 
                   
               
               
                   
                 GAGGCCAGGGGACAAGTTCACCGCTGCACACTATATGACCACAGACCTAAAAA 
                   
               
               
                   
                 AGTACTGCCTTAACTGGCGGCACCAGTCAGTCAAATTGTTCGCCAGAAGCCTG 
                   
               
               
                   
                 GATCGACTATTTGGGTTAGACCATGCTTTTTCTTGGATACACGTCCGTCTCACC 
                   
               
               
                   
                 AATAGCACTATGTACGTTGCTGACCCATTCAATCCACCAGACTCAGATGCATGC 
                   
               
               
                   
                 ACAAATTTAGACGACAATAAGAACACTGGGATTTTTATTATAAGTGCTCGAGGT 
                   
               
               
                   
                 GGTATAGAAGGCCTTCAACAGAAACTATGGACTGGCATATCAATTGCAATCGCC 
                   
               
               
                   
                 CAGGCGGCAGCAGCCCTCGAGGGCTTACGAATTGCTGCCACTTTGCAGGGGG 
                   
               
               
                   
                 ATAACCAGGTTTTAGCGATTACGAAAGAATTCATGACCCCAGTCTCGGAGGATG 
                   
               
               
                   
                 TAATCCACGAGCAGCTATCTGAAGCGATGTCGCGATACAAGAGGACTTTCACAT 
                   
               
               
                   
                 ACCTTAATTATTTAATGGGGCACCAATTGAAGGATAAAGAAACCATCCAATCCA 
                   
               
               
                   
                 GTGACTTCTTCGTTTACTCCAAAAGGATCTTCTTCAATGGGTCAATCCTAAGTCA 
                   
               
               
                   
                 ATGCCTCAAGAACTTCAGTAAACTCACTACCAATGCCACTACCCTTGCTGAGAA 
                   
               
               
                   
                 CACTGTAGCCGGCTGCAGTGACATCTCCTCATGCATAGCCCGTTGTGTGGAAA 
                   
               
               
                   
                 ACGGGTTGCCTAAGGATGCTGCATATGTTCAGAATATAATCATGACTCGGCTTC 
                   
               
               
                   
                 AACTGTTGCTAGATCACTACTATTCTATGCATGGTGGCATAAACTCAGAGTTAG 
                   
               
               
                   
                 AGCAGCCAACTCTAAGTATCCCTGTCCGAAACGCAACCTATTTACCATCTCAAT 
                   
               
               
                   
                 TAGGCGGTTACAATCATTTGAATATGACCCGACTATTCTGTCGCAATATCGGTG 
                   
               
               
                   
                 ACCCGCTTACTAGTTCTTGGGCAGAGTCAAAAAGACTAATGGATGTTGGCCTTC 
                   
               
               
                   
                 TCAGTCGTAAGTTCTTAGAGGGGATATTATGGAGACCCCCGGGAAGTGGGACA 
                   
               
               
                   
                 TTTTCAACACTCATGCTTGATCCGTTCGCACTTAACATTGATTACTTAAGGCCAC 
                   
               
               
                   
                 CAGAGACAATAATCCGAAAACACACCCAAAAAGTCTTGTTGCAGGATTGTCCTA 
                   
               
               
                   
                 ATCCTCTATTAGCAGGTGTAGTTGACCCGAACTACAACCAGGAATTAGAATTAT 
                   
               
               
                   
                 TAGCTCAGTTCCTGCTTGATCGGGAAACCGTTATTCCCAGGGCTGCCCATGCC 
                   
               
               
                   
                 ATCTTTGAACTGTCTGTCTTGGGAAGGAAAAAACATATACAAGGATTGGTTGAT 
                   
               
               
                   
                 ACTACAAAAACAATTATTCAGTGCTCATTAGAAAGACAGCCACTGTCCTGGAGG 
                   
               
               
                   
                 AAAGTTGAGAACATTGTAACCTACAATGCGCAGTATTTCCTCGGGGCCACCCA 
                   
               
               
                   
                 GCAGGTTGACACCAATATCTCAGAAAGGCAGTGGGTGATGCCAGGTAATTTCA 
                   
               
               
                   
                 AGAAGCTTGTATCTCTTGACGATTGCTCAGTCACGTTGTCCACTGTGTCACGGC 
                   
               
               
                   
                 GCATTTCTTGGGCCAATCTACTTAACTGGAGGGCTATAGATGGTTTGGAAACTC 
                   
               
               
                   
                 CAGATGTGATAGAGAGTATTGATGGCCGCCTTGTGCAATCATCCAATCAATGCG 
                   
               
               
                   
                 GCCTATGTAATCAAGGATTGGGCTCCTACTCCTGGTTCTTCTTGCCCTCCGGGT 
                   
               
               
                   
                 GTGTGTTCGACCGTCCACAAGATTCTCGAGTGGTTCCAAAGATGCCATACGTG 
                   
               
               
                   
                 GGATCCAAAACGGATGAGAGACAGACTGCGTCAGTGCAGGCTATACAGGGATC 
                   
               
               
                   
                 CACATGTCACCTTAGAGCAGCATTGAGACTTGTATCACTCTACCTTTGGGCCTA 
                   
               
               
                   
                 TGGAGATTCTGACATATCATGGCTAGAAGCCGCGACATTGGCTCAAACACGGT 
                   
               
               
                   
                 GCAATATTTCTCTTGATGACCTGCGGATCCTGAGCCCTCTTCCTTCCTCGGCAA 
                   
               
               
                   
                 ATTTACACCACAGATTGAATGACGGGGTAACACAAGTGAAATTCATGCCCGCCA 
                   
               
               
                   
                 CATCGAGCCGGGTGTCAAAGTTCGTCCAAATTTGCAATGACAACCAGAATCTTA 
                   
               
               
                   
                 TCCGTGATGATGGGAGTGTTGATTCCAATATGATTTATCAGCAGGTTATGATATT 
                   
               
               
                   
                 AGGGCTTGGAGAGATTGAATGTTTGTTAGCTGACCCAATCGATACAAACCCAGA 
                   
               
               
                   
                 ACAACTGATTCTTCACCTACACTCTGATAATTCTTGCTGTCTCCGGGAGATGCC 
                   
               
               
                   
                 AACGACCGGTTTTGTACCTGCTTTAGGATTGACCCCATGCTTAACTGTCCCAAA 
                   
               
               
                   
                 GCACAATCCGTATATTTATGATGATAGCCCAATACCCGGTGATTTGGATCAGAG 
                   
               
               
                   
                 GCTCATTCAAACCAAATTCTTTATGGGTTCTGACAATCTAGATAATCTTGATATC 
                   
               
               
                   
                 TACCAGCAGCGAGCTTTACTGAGTCGGTGTGTGGCTTATGACATTATCCAATCA 
                   
               
               
                   
                 GTATTCGCTTGCGATGCACCAGTATCTCAGAAGAATGATGCAATCCTTCACACT 
                   
               
               
                   
                 GACTACCATGAAAATTGGATCTCAGAGTTCCGATGGGGTGACCCTCGCATAAT 
                   
               
               
                   
                 CCAAGTAACAGCAGGTTACGAGTTAATTCTGTTCCTTGCATACCAGCTTTATTAT 
                   
               
               
                   
                 CTCAGAGTGAGGGGTGACCGTGCAATCCTGTGTTATATTGATAGGATACTCAAC 
                   
               
               
                   
                 AGGATGGTATCTTCCAATCTAGGCAGTCTCATCCAGACGCTCTCTCATCCGGA 
                   
               
               
                   
                 GATTAGGAGGAGATTTTCATTGAGTGATCAAGGGTTCCTTGTCGAAAGGGAGC 
                   
               
               
                   
                 TAGAGCCAGGTAAGCCACTGGTAAAACAAGCGGTTATGTTCCTAAGGGACTCA 
                   
               
               
                   
                 GTCCGCTGCGCTTTAGCAACTATCAAGGCAGGAATTGAGCCTGAGATCTCCCG 
                   
               
               
                   
                 AGGTGGCTGTACCCAGGATGAGCTGAGCTTTACCCTTAAGCACTTACTATGTC 
                   
               
               
                   
                 GGCGTCTCTGTATAATTGCTCTCATGCATTCGGAAGCAAAGAACTTGGTCAAAG 
                   
               
               
                   
                 TTAGAAACCTTCCAGTAGAGGAAAAAACCGCCTTACTATACCAGATGTTGATCA 
                   
               
               
                   
                 CTGAGGCCAATGCCAGGAGATCAGGGTCTGCTAGTATCATCATAAGCTTAGTTT 
                   
               
               
                   
                 CAGCACCCCAGTGGGACATTCATACACCAGCGTTGTATTTTGTATCAAAGAAAA 
                   
               
               
                   
                 TGCTGGGGATGCTCAAAAGGTCAACCACACCCTTGGATATAAGTGACCTTTCTG 
                   
               
               
                   
                 AGAGCCAGAACCTCACACCAACAGAATTGAATGATGTTCCTGGTCACATGGCA 
                   
               
               
                   
                 GAGGAATTTCCCTGTTTGTTTAGCAGTTATAACGCTACATATGAAGACACAATTA 
                   
               
               
                   
                 CTTACAATCCAATGACTGAAAAACTCGCAGTGCACTTGGACAATGGTTCCACCC 
                   
               
               
                   
                 CTTCCAGAGCGCTTGGTCGTCACTACATCCTGCGACCCCTTGGGCTTTACTCG 
                   
               
               
                   
                 TCTGCATGGTACCGGTCTGCAGCACTATTAGCGTCAGGGGCCCTCAGTGGGTT 
                   
               
               
                   
                 GCCTGAGGGGTCAAGCCTGTACTTGGGAGAGGGGTATGGGACCACCATGACT 
                   
               
               
                   
                 CTACTTGAGCCCGTTGTCAAGTCCTCAACTGTTTACTACCATACATTGTTTGACC 
                   
               
               
                   
                 CAACCCGGAATCCTTCACAGCGGAACTACAAACCAGAACCGCGGGTATTCACT 
                   
               
               
                   
                 GATTCCATTTGGTACAAGGATGATTTCACACGACCACCTGGTGGCATTGTAAAT 
                   
               
               
                   
                 CTATGGGGTGAAGACGTACGTCAGAGTGATATTACACAGAAAGACACGGTTAA 
                   
               
               
                   
                 TTTCATATTATCTCGGGTCCCGCCAAAATCACTCAAATTGATACACGTTGATATT 
                   
               
               
                   
                 GAGTTCTCCCCAGACTCTGATGTACGGACGCTACTATCTGGCTATTCCCATTGT 
                   
               
               
                   
                 GCACTATTGGCCTACTGGCTACTGCAACCTGGAGGGCGATTTGCGGTTAGAGT 
                   
               
               
                   
                 TTTCTTAAGTGACCATATCATAGTCAACTTGGTCACTGCCATTCTGTCCGCTTTT 
                   
               
               
                   
                 GACTCTAATCTGGTGTGCATTGCGTCAGGATTGACACACAAGGATGATGGGGC 
                   
               
               
                   
                 AGGTTATATTTGTGCAAAGAAGCTTGCAAATGTTGAGGCTTCAAGAATTGAGTA 
                   
               
               
                   
                 TTACTTGAGGATGGTCCACGGCTGTGTTGACTCATTAAAAATTCCTCATCAATTA 
                   
               
               
                   
                 GGAATCATTAAATGGGCTGAGGGTGAAGTGTCCCGACTTACCAAAAAGGCGGA 
                   
               
               
                   
                 TGATGAAATAAACTGGCGGTTAGGTGATCCAGTTACCAGATCATTTGATCCGGT 
                   
               
               
                   
                 TTCTGAGCTAATAATTGCGCGAACAGGGGGATCAGTATTAATGGAATACGGGA 
                   
               
               
                   
                 CTTTTACTAACCTCAGGTGTGCGAACTTGGCAGATACATATAAACTTTTGGCTTC 
                   
               
               
                   
                 AATTGTAGAGACCACCTTAATGGAAATAAGGGTTGAGCAAGATCAGTTGGAAGA 
                   
               
               
                   
                 TGATTCGAGGAGACAAATCCAGGTAGTCCCTGC1111AATACAAGATCCGGGG 
                   
               
               
                   
                 GAAGGATCCGTACATTGATTGAGTGTGCTCAGCTGCAGGTCATAGATGTTATCT 
                   
               
               
                   
                 GTGTGAACATAGATCACCTCTTTCCCAAACACCGACATGCTCTTGTCACACAAC 
                   
               
               
                   
                 TTACTTACCAGTCAGTGTGCCTTGGGGACTTGATTGAAGGCCCCCAAATTAAGA 
                   
               
               
                   
                 CATATCTAAGGGCCAGGAAGTGGATCCAACGTAGGGGACTCAATGAGACAATT 
                   
               
               
                   
                 AACCATATCATCACTGGACAAGTGTCGCGGAATAAGGCAAGGGATTTTTTCAAG 
                   
               
               
                   
                 AGGCGCCTGAAGTTGGTTGGCTTTTCGCTCTGTGGCGGTTGGGGCTACCTCTC 
                   
               
               
                   
                 ACTTTAGCTGCTTAGATTGTTGATTATTATGAATAATCGGAGTCGAAATCGTAAA 
                   
               
               
                   
                 TAGAAAGACATAAAATTGCAAATAAGCAATGATCGTATTAATATTTAATAAAAAAT 
                   
               
               
                   
                 ATGTCTTTTATTTCTTGCGCGCGGCCGGCATGGTCCCAGCCTCCTCGCTGGCG 
                   
               
               
                   
                 CCGGCTGGGCAACATTCCGAGGGGACCGTCCCCTCGGTAATGGCGAATGGGA 
                   
               
               
                   
                 CGTCGACTGCTAACAAAGCCCGAAAGGAAGCTGAGTTGGCTGCTGCCACCGCT 
                   
               
               
                   
                 GAGCAATAACTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTT 
                   
               
               
                   
                 TTTGCTGAAAGGAGGAACTATATGCGCGCAGATCTGTCATGATGATCATTGCAA 
                   
               
               
                   
                 TTGGATCCATATATAGGGCCCGGGTTATAATTACCTCAGGTCGACGTCCCATG 
                   
               
               
                   
                 GCCATTCGAATTCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCC 
                   
               
               
                   
                 GCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGG 
                   
               
               
                   
                 GTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTT 
                   
               
               
                   
                 TCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCG 
                   
               
               
                   
                 GGGAGAGGCGGTTTGCGTATTGGGCGC 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 VEGF-C/VEGF-D SEQUENCES 
               
            
           
           
               
               
               
            
               
                   
                   
                 SEQ ID 
               
               
                 Description 
                 Sequence 
                 NO. 
               
               
                   
               
            
           
           
               
               
               
            
               
                 mouse VEGF- 
                 ATGCACTTGCTGTGCTTCTTGTCTCTGGCGTGTTCCCTGCTCG 
                 1 
               
               
                 C full length 
                 CCGCTGCGCTGATCCCCAGTCCGCGCGAGGCGCCCGCCACCG 
                   
               
               
                 wt native 
                 TCGCCGCCTTCGAGTCGGGACTGGGCTTCTCGGAAGCGGAGC 
                   
               
               
                   
                 CCGACGGGGGCGAGGTCAAGGCTTTTGAAGGCAAAGACCTG 
                   
               
               
                   
                 GAGGAGCAGTTGCGGTCTGTGTCCAGCGTAGATGAGCTGATG 
                   
               
               
                   
                 TCTGTCCTGTACCCAGACTACTGGAAAATGTACAAGTGCCAG 
                   
               
               
                   
                 CTGCGGAAAGGCGGCTGGCAGCAGCCCACCCTCAATACCAGG 
                   
               
               
                   
                 ACAGGGGACAGTGTAAAATTTGCTGCTGCACATTATAACACA 
                   
               
               
                   
                 GAGATCCTGAAAAGTATTGATAATGAGTGGAGAAAGACTCA 
                   
               
               
                   
                 ATGCATGCCACGTGAGGTGTGTATAGATGTGGGGAAGGAGTT 
                   
               
               
                   
                 TGGAGCAGCCACAAACACCTTCTTTAAACCTCCATGTGTGTCC 
                   
               
               
                   
                 GTCTACAGATGTGGGGGTTGCTGCAACAGCGAGGGGCTGCAG 
                   
               
               
                   
                 TGCATGAACACCAGCACAGGTTACCTCAGCAAGACGTTGTTT 
                   
               
               
                   
                 GAAATTACAGTGCCTCTCTCACAAGGCCCCAAACCAGTCACA 
                   
               
               
                   
                 ATCAGTTTTGCCAATCACACTTCCTGCCGGTGCATGTCTAAAC 
                   
               
               
                   
                 TGGATGTTTACAGACAAGTTCATTCAATTATTAGACGTTCTCT 
                   
               
               
                   
                 GCCAGCAACATTACCACAGTGTCAGGCAGCTAACAAGACATG 
                   
               
               
                   
                 TCCAACAAACTATGTGTGGAATAACTACATGTGCCGATGCCT 
                   
               
               
                   
                 GGCTCAGCAGGATTTTATCTTTTATTCAAATGTTGAAGATGAC 
                   
               
               
                   
                 TCAACCAATGGATTCCATGATGTCTGTGGACCCAACAAGGAG 
                   
               
               
                   
                 CTGGATGAAGACACCTGTCAGTGTGTCTGCAAGGGGGGGCTT 
                   
               
               
                   
                 CGGCCATCTAGTTGTGGACCCCACAAAGAACTAGATAGAGAC 
                   
               
               
                   
                 TCATGTCAGTGTGTCTGTAAAAACAAACTTTTCCCTAATTCAT 
                   
               
               
                   
                 GTGGAGCCAACAGGGAATTTGATGAGAATACATGTCAGTGTG 
                   
               
               
                   
                 TATGTAAAAGAACGTGTCCAAGAAATCAGCCCCTGAATCCTG 
                   
               
               
                   
                 GGAAATGTGCCTGTGAATGTACAGAAAACACACAGAAGTGCT 
                   
               
               
                   
                 TCCTTAAAGGGAAGAAGTTCCACCATCAAACATGCAGTTGTT 
                   
               
               
                   
                 ACAGAAGACCGTGTGCGAATCGACTGAAGCATTGTGATCCAG 
                   
               
               
                   
                 GACTGTCCTTTAGTGAAGAAGTATGCCGCTGTGTCCCATCGTA 
                   
               
               
                   
                 TTGGAAAAGGCCACATCTGAACTAA 
                   
               
               
                   
               
               
                 mouse VEGF- 
                 ATGCACTTGCTGTGCTTCTTGTCTCTGGCGTGTTCCCTGCTCG 
                 2 
               
               
                 C full length 
                 CCGCTGCGCTGATCCCCAGTCCGCGCGAGGCGCCCGCCACCG 
                   
               
               
                 Cys152Ser 
                 TCGCCGCCTTCGAGTCGGGACTGGGCTTCTCGGAAGCGGAGC 
                   
               
               
                 mutation 
                 CCGACGGGGGCGAGGTCAAGGCTTTTGAAGGCAAAGACCTG 
                   
               
               
                 native 
                 GAGGAGCAGTTGCGGTCTGTGTCCAGCGTAGATGAGCTGATG 
                   
               
               
                   
                 TCTGTCCTGTACCCAGACTACTGGAAAATGTACAAGTGCCAG 
                   
               
               
                   
                 CTGCGGAAAGGCGGCTGGCAGCAGCCCACCCTCAATACCAGG 
                   
               
               
                   
                 ACAGGGGACAGTGTAAAATTTGCTGCTGCACATTATAACACA 
                   
               
               
                   
                 GAGATCCTGAAAAGTATTGATAATGAGTGGAGAAAGACTCA 
                   
               
               
                   
                 ATGCATGCCACGTGAGGTGTGTATAGATGTGGGGAAGGAGTT 
                   
               
               
                   
                 TGGAGCAGCCACAAACACCTTCTTTAAACCTCCATCTGTGTCC 
                   
               
               
                   
                 GTCTACAGATGTGGGGGTTGCTGCAACAGCGAGGGGCTGCAG 
                   
               
               
                   
                 TGCATGAACACCAGCACAGGTTACCTCAGCAAGACGTTGTTT 
                   
               
               
                   
                 GAAATTACAGTGCCTCTCTCACAAGGCCCCAAACCAGTCACA 
                   
               
               
                   
                 ATCAGTTTTGCCAATCACACTTCCTGCCGGTGCATGTCTAAAC 
                   
               
               
                   
                 TGGATGTTTACAGACAAGTTCATTCAATTATTAGACGTTCTCT 
                   
               
               
                   
                 GCCAGCAACATTACCACAGTGTCAGGCAGCTAACAAGACATG 
                   
               
               
                   
                 TCCAACAAACTATGTGTGGAATAACTACATGTGCCGATGCCT 
                   
               
               
                   
                 GGCTCAGCAGGATTTTATCTTTTATTCAAATGTTGAAGATGAC 
                   
               
               
                   
                 TCAACCAATGGATTCCATGATGTCTGTGGACCCAACAAGGAG 
                   
               
               
                   
                 CTGGATGAAGACACCTGTCAGTGTGTCTGCAAGGGGGGGCTT 
                   
               
               
                   
                 CGGCCATCTAGTTGTGGACCCCACAAAGAACTAGATAGAGAC 
                   
               
               
                   
                 TCATGTCAGTGTGTCTGTAAAAACAAACTTTTCCCTAATTCAT 
                   
               
               
                   
                 GTGGAGCCAACAGGGAATTTGATGAGAATACATGTCAGTGTG 
                   
               
               
                   
                 TATGTAAAAGAACGTGTCCAAGAAATCAGCCCCTGAATCCTG 
                   
               
               
                   
                 GGAAATGTGCCTGTGAATGTACAGAAAACACACAGAAGTGCT 
                   
               
               
                   
                 TCCTTAAAGGGAAGAAGTTCCACCATCAAACATGCAGTTGTT 
                   
               
               
                   
                 ACAGAAGACCGTGTGCGAATCGACTGAAGCATTGTGATCCAG 
                   
               
               
                   
                 GACTGTCCTTTAGTGAAGAAGTATGCCGCTGTGTCCCATCGTA 
                   
               
               
                   
                 TTGGAAAAGGCCACATCTGAACTAA 
                   
               
               
                   
               
               
                 mouse VEGF- 
                 ATGCACTTGCTGTGCTTCTTGTCTCTGGCGTGTTCCCTGCTCG 
                 3 
               
               
                 C full length 
                 CCGCTGCGCTGATCCCCAGTCCGCGCGAGGCGCCCGCCACCG 
                   
               
               
                 Cys133Ala 
                 TCGCCGCCTTCGAGTCGGGACTGGGCTTCTCGGAAGCGGAGC 
                   
               
               
                 mutation 
                 CCGACGGGGGCGAGGTCAAGGCTTTTGAAGGCAAAGACCTG 
                   
               
               
                 native 
                 GAGGAGCAGTTGCGGTCTGTGTCCAGCGTAGATGAGCTGATG 
                   
               
               
                   
                 TCTGTCCTGTACCCAGACTACTGGAAAATGTACAAGTGCCAG 
                   
               
               
                   
                 CTGCGGAAAGGCGGCTGGCAGCAGCCCACCCTCAATACCAGG 
                   
               
               
                   
                 ACAGGGGACAGTGTAAAATTTGCTGCTGCACATTATAACACA 
                   
               
               
                   
                 GAGATCCTGAAAAGTATTGATAATGAGTGGAGAAAGACTCA 
                   
               
               
                   
                 ATGCATGCCACGTGAGGTGGCTATAGATGTGGGGAAGGAGTT 
                   
               
               
                   
                 TGGAGCAGCCACAAACACCTTCTTTAAACCTCCATGTGTGTCC 
                   
               
               
                   
                 GTCTACAGATGTGGGGGTTGCTGCAACAGCGAGGGGCTGCAG 
                   
               
               
                   
                 TGCATGAACACCAGCACAGGTTACCTCAGCAAGACGTTGTTT 
                   
               
               
                   
                 GAAATTACAGTGCCTCTCTCACAAGGCCCCAAACCAGTCACA 
                   
               
               
                   
                 ATCAGTTTTGCCAATCACACTTCCTGCCGGTGCATGTCTAAAC 
                   
               
               
                   
                 TGGATGTTTACAGACAAGTTCATTCAATTATTAGACGTTCTCT 
                   
               
               
                   
                 GCCAGCAACATTACCACAGTGTCAGGCAGCTAACAAGACATG 
                   
               
               
                   
                 TCCAACAAACTATGTGTGGAATAACTACATGTGCCGATGCCT 
                   
               
               
                   
                 GGCTCAGCAGGATTTTATCTTTTATTCAAATGTTGAAGATGAC 
                   
               
               
                   
                 TCAACCAATGGATTCCATGATGTCTGTGGACCCAACAAGGAG 
                   
               
               
                   
                 CTGGATGAAGACACCTGTCAGTGTGTCTGCAAGGGGGGGCTT 
                   
               
               
                   
                 CGGCCATCTAGTTGTGGACCCCACAAAGAACTAGATAGAGAC 
                   
               
               
                   
                 TCATGTCAGTGTGTCTGTAAAAACAAACTTTTCCCTAATTCAT 
                   
               
               
                   
                 GTGGAGCCAACAGGGAATTTGATGAGAATACATGTCAGTGTG 
                   
               
               
                   
                 TATGTAAAAGAACGTGTCCAAGAAATCAGCCCCTGAATCCTG 
                   
               
               
                   
                 GGAAATGTGCCTGTGAATGTACAGAAAACACACAGAAGTGCT 
                   
               
               
                   
                 TCCTTAAAGGGAAGAAGTTCCACCATCAAACATGCAGTTGTT 
                   
               
               
                   
                 ACAGAAGACCGTGTGCGAATCGACTGAAGCATTGTGATCCAG 
                   
               
               
                   
                 GACTGTCCTTTAGTGAAGAAGTATGCCGCTGTGTCCCATCGTA 
                   
               
               
                   
                 TTGGAAAAGGCCACATCTGAACTAA 
                   
               
               
                   
               
               
                 mouse VEGF- 
                 GCACATTATAACACAGAGATCCTGAAAAGTATTGATAATGAG 
                 4 
               
               
                 C mature 
                 TGGAGAAAGACTCAATGCATGCCACGTGAGGTGTGTATAGAT 
                   
               
               
                 (dNdC) wt 
                 GTGGGGAAGGAGTTTGGAGCAGCCACAAACACCTTCTTTAAA 
                   
               
               
                 native 
                 CCTCCATGTGTGTCCGTCTACAGATGTGGGGGTTGCTGCAAC 
                   
               
               
                   
                 AGCGAGGGGCTGCAGTGCATGAACACCAGCACAGGTTACCTC 
                   
               
               
                   
                 AGCAAGACGTTGTTTGAAATTACAGTGCCTCTCTCACAAGGC 
                   
               
               
                   
                 CCCAAACCAGTCACAATCAGTTTTGCCAATCACACTTCCTGCC 
                   
               
               
                   
                 GGTGCATGTCTAAACTGGATGTTTACAGACAAGTTCATTCAA 
                   
               
               
                   
                 TTATTAGACGT 
                   
               
               
                   
               
               
                 mouse VEGF- 
                 GCACATTATAACACAGAGATCCTGAAAAGTATTGATAATGAG 
                 5 
               
               
                 C mature 
                 TGGAGAAAGACTCAATGCATGCCACGTGAGGTGTGTATAGAT 
                   
               
               
                 (dNdC) 
                 GTGGGGAAGGAGTTTGGAGCAGCCACAAACACCTTCTTTAAA 
                   
               
               
                 Cys152Ser 
                 CCTCCATCTGTGTCCGTCTACAGATGTGGGGGTTGCTGCAACA 
                   
               
               
                 mutation 
                 GCGAGGGGCTGCAGTGCATGAACACCAGCACAGGTTACCTCA 
                   
               
               
                 native 
                 GCAAGACGTTGTTTGAAATTACAGTGCCTCTCTCACAAGGCC 
                   
               
               
                   
                 CCAAACCAGTCACAATCAGTTTTGCCAATCACACTTCCTGCCG 
                   
               
               
                   
                 GTGCATGTCTAAACTGGATGTTTACAGACAAGTTCATTCAATT 
                   
               
               
                   
                 ATTAGACGT 
                   
               
               
                   
               
               
                 mouse VEGF- 
                 GCACATTATAACACAGAGATCCTGAAAAGTATTGATAATGAG 
                 6 
               
               
                 C mature 
                 TGGAGAAAGACTCAATGCATGCCACGTGAGGTGGCTATAGAT 
                   
               
               
                 (dNdC) 
                 GTGGGGAAGGAGTTTGGAGCAGCCACAAACACCTTCTTTAAA 
                   
               
               
                 Cys133Ala 
                 CCTCCATGTGTGTCCGTCTACAGATGTGGGGGTTGCTGCAAC 
                   
               
               
                 mutation 
                 AGCGAGGGGCTGCAGTGCATGAACACCAGCACAGGTTACCTC 
                   
               
               
                 native 
                 AGCAAGACGTTGTTTGAAATTACAGTGCCTCTCTCACAAGGC 
                   
               
               
                   
                 CCCAAACCAGTCACAATCAGTTTTGCCAATCACACTTCCTGCC 
                   
               
               
                   
                 GGTGCATGTCTAAACTGGATGTTTACAGACAAGTTCATTCAA 
                   
               
               
                   
                 TTATTAGACGT 
                   
               
               
                   
               
               
                 mouse VEGF- 
                 ATGCATCTGCTGTGTTTCCTGTCGCTCGCCTGCTCACTGCTGG 
                 7 
               
               
                 C full length 
                 CGGCGGCACTTATCCCGTCCCCACGGGAGGCTCCTGCCACCG 
                   
               
               
                 wt codon 
                 TGGCCGCCTTCGAATCTGGGCTGGGCTTCAGCGAAGCCGAGC 
                   
               
               
                 optimized 1 
                 CCGATGGCGGAGAGGTCAAGGCATTCGAAGGAAAGGACCTC 
                   
               
               
                 (MS) 
                 GAAGAACAGCTGAGATCCGTGTCCTCCGTGGACGAACTCATG 
                   
               
               
                 (“SNI 
                 TCCGTCCTGTACCCCGATTACTGGAAGATGTACAAATGCCAG 
                   
               
               
                 VEGF-C FL 
                 CTCCGGAAGGGCGGTTGGCAGCAGCCCACTCTGAACACTCGC 
                   
               
               
                 WT” or “FL- 
                 ACGGGAGATTCCGTGAAGTTTGCCGCCGCCCACTACAATACT 
                   
               
               
                 WT”) 
                 GAGATTCTCAAGTCCATCGACAACGAATGGAGGAAAACCCA 
                   
               
               
                   
                 GTGTATGCCGCGCGAAGTCTGCATTGACGTGGGAAAGGAGTT 
                   
               
               
                   
                 CGGCGCTGCCACCAACACCTTCTTTAAGCCTCCCTGCGTGTCG 
                   
               
               
                   
                 GTGTATCGCTGCGGGGGATGCTGCAACAGCGAAGGCCTTCAG 
                   
               
               
                   
                 TGCATGAACACCAGCACCGGATACCTCAGCAAGACTCTCTTC 
                   
               
               
                   
                 GAAATCACTGTGCCGCTGTCACAAGGCCCGAAGCCTGTGACC 
                   
               
               
                   
                 ATTTCCTTCGCCAACCACACCTCCTGTCGGTGCATGAGCAAGC 
                   
               
               
                   
                 TGGATGTGTACAGACAGGTGCACTCCATCATCCGGAGATCGT 
                   
               
               
                   
                 TGCCTGCCACCCTGCCGCAGTGCCAAGCGGCTAACAAGACCT 
                   
               
               
                   
                 GTCCCACCAACTACGTGTGGAACAACTATATGTGTCGGTGCC 
                   
               
               
                   
                 TGGCACAGCAGGACTTTATCTTCTACTCCAACGTGGAGGACG 
                   
               
               
                   
                 ACTCGACTAACGGTTTCCACGACGTGTGCGGACCCAACAAGG 
                   
               
               
                   
                 AGCTGGATGAGGATACTTGTCAGTGCGTGTGCAAGGGTGGCC 
                   
               
               
                   
                 TGCGCCCGTCCTCCTGCGGACCACATAAGGAACTGGACAGGG 
                   
               
               
                   
                 ACTCGTGCCAATGCGTCTGCAAGAACAAGCTGTTCCCTAACT 
                   
               
               
                   
                 CCTGCGGGGCGAACCGCGAATTCGACGAGAACACCTGTCAGT 
                   
               
               
                   
                 GTGTGTGCAAGCGGACTTGCCCGAGGAATCAGCCTCTTAACC 
                   
               
               
                   
                 CCGGAAAATGCGCCTGCGAATGCACAGAGAACACCCAGAAG 
                   
               
               
                   
                 TGCTTCTTGAAAGGGAAGAAGTTCCACCACCAAACCTGTTCA 
                   
               
               
                   
                 TGCTACCGGCGCCCATGTGCCAACCGGCTGAAGCACTGCGAC 
                   
               
               
                   
                 CCGGGATTGAGCTTCAGCGAGGAGGTCTGCAGATGCGTGCCG 
                   
               
               
                   
                 TCATACTGGAAGCGACCTCATCTGAATTAGTGA 
                   
               
               
                   
               
               
                 mouse VEGF- 
                 ATGCATCTGCTGTGTTTCCTGTCGCTCGCCTGCTCACTGCTGG 
                 8 
               
               
                 C full length 
                 CGGCGGCACTTATCCCGTCCCCACGGGAGGCTCCTGCCACCG 
                   
               
               
                 Cys152Ser 
                 TGGCCGCCTTCGAATCTGGGCTGGGCTTCAGCGAAGCCGAGC 
                   
               
               
                 mutation 
                 CCGATGGCGGAGAGGTCAAGGCATTCGAAGGAAAGGACCTC 
                   
               
               
                 codon 
                 GAAGAACAGCTGAGATCCGTGTCCTCCGTGGACGAACTCATG 
                   
               
               
                 optimized 1 
                 TCCGTCCTGTACCCCGATTACTGGAAGATGTACAAATGCCAG 
                   
               
               
                 (MS) 
                 CTCCGGAAGGGCGGTTGGCAGCAGCCCACTCTGAACACTCGC 
                   
               
               
                 (“SN3 
                 ACGGGAGATTCCGTGAAGTTTGCCGCCGCCCACTACAATACT 
                   
               
               
                 VEGF-C FL 
                 GAGATTCTCAAGTCCATCGACAACGAATGGAGGAAAACCCA 
                   
               
               
                 152S” or “FL 
                 GTGTATGCCGCGCGAAGTCTGCATTGACGTGGGAAAGGAGTT 
                   
               
               
                 -152S”) 
                 CGGCGCTGCCACCAACACCTTCTTTAAGCCTCCCTCCGTGTCG 
                   
               
               
                   
                 GTGTATCGCTGCGGGGGATGCTGCAACAGCGAAGGCCTTCAG 
                   
               
               
                   
                 TGCATGAACACCAGCACCGGATACCTCAGCAAGACTCTCTTC 
                   
               
               
                   
                 GAAATCACTGTGCCGCTGTCACAAGGCCCGAAGCCTGTGACC 
                   
               
               
                   
                 ATTTCCTTCGCCAACCACACCTCCTGTCGGTGCATGAGCAAGC 
                   
               
               
                   
                 TGGATGTGTACAGACAGGTGCACTCCATCATCCGGAGATCGT 
                   
               
               
                   
                 TGCCTGCCACCCTGCCGCAGTGCCAAGCGGCTAACAAGACCT 
                   
               
               
                   
                 GTCCCACCAACTACGTGTGGAACAACTATATGTGTCGGTGCC 
                   
               
               
                   
                 TGGCACAGCAGGACTTTATCTTCTACTCCAACGTGGAGGACG 
                   
               
               
                   
                 ACTCGACTAACGGTTTCCACGACGTGTGCGGACCCAACAAGG 
                   
               
               
                   
                 AGCTGGATGAGGATACTTGTCAGTGCGTGTGCAAGGGTGGCC 
                   
               
               
                   
                 TGCGCCCGTCCTCCTGCGGACCACATAAGGAACTGGACAGGG 
                   
               
               
                   
                 ACTCGTGCCAATGCGTCTGCAAGAACAAGCTGTTCCCTAACT 
                   
               
               
                   
                 CCTGCGGGGCGAACCGCGAATTCGACGAGAACACCTGTCAGT 
                   
               
               
                   
                 GTGTGTGCAAGCGGACTTGCCCGAGGAATCAGCCTCTTAACC 
                   
               
               
                   
                 CCGGAAAATGCGCCTGCGAATGCACAGAGAACACCCAGAAG 
                   
               
               
                   
                 TGCTTCTTGAAAGGGAAGAAGTTCCACCACCAAACCTGTTCA 
                   
               
               
                   
                 TGCTACCGGCGCCCATGTGCCAACCGGCTGAAGCACTGCGAC 
                   
               
               
                   
                 CCGGGATTGAGCTTCAGCGAGGAGGTCTGCAGATGCGTGCCG 
                   
               
               
                   
                 TCATACTGGAAGCGACCTCATCTGAATTAGTGA 
                   
               
               
                   
               
               
                 mouse VEGF- 
                 ATGCATCTGCTGTGTTTCCTGTCGCTCGCCTGCTCACTGCTGG 
                 9 
               
               
                 C full length 
                 CGGCGGCACTTATCCCGTCCCCACGGGAGGCTCCTGCCACCG 
                   
               
               
                 Cys133Ala 
                 TGGCCGCCTTCGAATCTGGGCTGGGCTTCAGCGAAGCCGAGC 
                   
               
               
                 mutation 
                 CCGATGGCGGAGAGGTCAAGGCATTCGAAGGAAAGGACCTC 
                   
               
               
                 codon 
                 GAAGAACAGCTGAGATCCGTGTCCTCCGTGGACGAACTCATG 
                   
               
               
                 optimized 1 
                 TCCGTCCTGTACCCCGATTACTGGAAGATGTACAAATGCCAG 
                   
               
               
                 (MS) 
                 CTCCGGAAGGGCGGTTGGCAGCAGCCCACTCTGAACACTCGC 
                   
               
               
                 (“SN2 VEGF- 
                 ACGGGAGATTCCGTGAAGTTTGCCGCCGCCCACTACAATACT 
                   
               
               
                 CFL 133A” 
                 GAGATTCTCAAGTCCATCGACAACGAATGGAGGAAAACCCA 
                   
               
               
                 or “FL- 
                 GTGTATGCCGCGCGAAGTCGCCATTGACGTGGGAAAGGAGTT 
                   
               
               
                 133A”) 
                 CGGCGCTGCCACCAACACCTTCTTTAAGCCTCCCTGCGTGTCG 
                   
               
               
                   
                 GTGTATCGCTGCGGGGGATGCTGCAACAGCGAAGGCCTTCAG 
                   
               
               
                   
                 TGCATGAACACCAGCACCGGATACCTCAGCAAGACTCTCTTC 
                   
               
               
                   
                 GAAATCACTGTGCCGCTGTCACAAGGCCCGAAGCCTGTGACC 
                   
               
               
                   
                 ATTTCCTTCGCCAACCACACCTCCTGTCGGTGCATGAGCAAGC 
                   
               
               
                   
                 TGGATGTGTACAGACAGGTGCACTCCATCATCCGGAGATCGT 
                   
               
               
                   
                 TGCCTGCCACCCTGCCGCAGTGCCAAGCGGCTAACAAGACCT 
                   
               
               
                   
                 GTCCCACCAACTACGTGTGGAACAACTATATGTGTCGGTGCC 
                   
               
               
                   
                 TGGCACAGCAGGACTTTATCTTCTACTCCAACGTGGAGGACG 
                   
               
               
                   
                 ACTCGACTAACGGTTTCCACGACGTGTGCGGACCCAACAAGG 
                   
               
               
                   
                 AGCTGGATGAGGATACTTGTCAGTGCGTGTGCAAGGGTGGCC 
                   
               
               
                   
                 TGCGCCCGTCCTCCTGCGGACCACATAAGGAACTGGACAGGG 
                   
               
               
                   
                 ACTCGTGCCAATGCGTCTGCAAGAACAAGCTGTTCCCTAACT 
                   
               
               
                   
                 CCTGCGGGGCGAACCGCGAATTCGACGAGAACACCTGTCAGT 
                   
               
               
                   
                 GTGTGTGCAAGCGGACTTGCCCGAGGAATCAGCCTCTTAACC 
                   
               
               
                   
                 CCGGAAAATGCGCCTGCGAATGCACAGAGAACACCCAGAAG 
                   
               
               
                   
                 TGCTTCTTGAAAGGGAAGAAGTTCCACCACCAAACCTGTTCA 
                   
               
               
                   
                 TGCTACCGGCGCCCATGTGCCAACCGGCTGAAGCACTGCGAC 
                   
               
               
                   
                 CCGGGATTGAGCTTCAGCGAGGAGGTCTGCAGATGCGTGCCG 
                   
               
               
                   
                 TCATACTGGAAGCGACCTCATCTGAATTAGTGA 
                   
               
               
                   
               
               
                 mouse VEGF- 
                 GCCCACTACAATACTGAGATTCTCAAGTCCATCGACAACGAA 
                 10 
               
               
                 C mature 
                 TGGAGGAAAACCCAGTGTATGCCGCGCGAAGTCTGCATTGAC 
                   
               
               
                 (dNdC) wt 
                 GTGGGAAAGGAGTTCGGCGCTGCCACCAACACCTTCTTTAAG 
                   
               
               
                 codon 
                 CCTCCCTGCGTGTCGGTGTATCGCTGCGGGGGATGCTGCAAC 
                   
               
               
                 optimized 1 
                 AGCGAAGGCCTTCAGTGCATGAACACCAGCACCGGATACCTC 
                   
               
               
                 (MS) 
                 AGCAAGACTCTCTTCGAAATCACTGTGCCGCTGTCACAAGGC 
                   
               
               
                 (SN4 
                 CCGAAGCCTGTGACCATTTCCTTCGCCAACCACACCTCCTGTC 
                   
               
               
                 VEGF-C 
                 GGTGCATGAGCAAGCTGGATGTGTACAGACAGGTGCACTCCA 
                   
               
               
                 DNDC WT” 
                 TCATCCGGAGA 
                   
               
               
                 or “dNdC- 
                   
                   
               
               
                 WT”) 
                   
                   
               
               
                   
               
               
                 mouse VEGF- 
                 GCCCACTACAATACTGAGATTCTCAAGTCCATCGACAACGAA 
                 11 
               
               
                 C mature 
                 TGGAGGAAAACCCAGTGTATGCCGCGCGAAGTCTGCATTGAC 
                   
               
               
                 (dNdC) 
                 GTGGGAAAGGAGTTCGGCGCTGCCACCAACACCTTCTTTAAG 
                   
               
               
                 Cys152Ser 
                 CCTCCCTCCGTGTCGGTGTATCGCTGCGGGGGATGCTGCAAC 
                   
               
               
                 mutation 
                 AGCGAAGGCCTTCAGTGCATGAACACCAGCACCGGATACCTC 
                   
               
               
                 codon 
                 AGCAAGACTCTCTTCGAAATCACTGTGCCGCTGTCACAAGGC 
                   
               
               
                 optimized 1 
                 CCGAAGCCTGTGACCATTTCCTTCGCCAACCACACCTCCTGTC 
                   
               
               
                 (MS) 
                 GGTGCATGAGCAAGCTGGATGTGTACAGACAGGTGCACTCCA 
                   
               
               
                 (SN6 VEGF- 
                 TCATCCGGAGA 
                   
               
               
                 CDNDC 
                   
                   
               
               
                 152S” or 
                   
                   
               
               
                 “dNdC- 
                   
                   
               
               
                 152S”) 
                   
                   
               
               
                   
               
               
                 mouse VEGF- 
                 GCCCACTACAATACTGAGATTCTCAAGTCCATCGACAACGAA 
                 12 
               
               
                 C mature 
                 TGGAGGAAAACCCAGTGTATGCCGCGCGAAGTCGCCATTGAC 
                   
               
               
                 (dNdC) 
                 GTGGGAAAGGAGTTCGGCGCTGCCACCAACACCTTCTTTAAG 
                   
               
               
                 Cys133Ala 
                 CCTCCCTGCGTGTCGGTGTATCGCTGCGGGGGATGCTGCAAC 
                   
               
               
                 mutation 
                 AGCGAAGGCCTTCAGTGCATGAACACCAGCACCGGATACCTC 
                   
               
               
                 codon 
                 AGCAAGACTCTCTTCGAAATCACTGTGCCGCTGTCACAAGGC 
                   
               
               
                 optimized 1 
                 CCGAAGCCTGTGACCATTTCCTTCGCCAACCACACCTCCTGTC 
                   
               
               
                 (MS) 
                 GGTGCATGAGCAAGCTGGATGTGTACAGACAGGTGCACTCCA 
                   
               
               
                 (“SN5 VEGF- 
                 TCATCCGGAGA 
                   
               
               
                 CDNDC 
                   
                   
               
               
                 133A” or 
                   
                   
               
               
                 “dNdC- 
                   
                   
               
               
                 133A”) 
                   
                   
               
               
                   
               
               
                 mouse VEGF- 
                 ATGCACCTGCTGTGCTTCCTGAGCCTGGCCTGCAGCCTGCTGG 
                 13 
               
               
                 C full length 
                 CCGCCGCCCTGATCCCCAGCCCCAGAGAGGCCCCCGCCACCG 
                   
               
               
                 wt codon 
                 TGGCCGCCTTCGAGAGCGGCCTGGGCTTCAGCGAGGCCGAGC 
                   
               
               
                 optimized 2 
                 CCGACGGCGGCGAGGTGAAGGCCTTCGAGGGCAAGGACCTG 
                   
               
               
                 (AGS) 
                 GAGGAGCAGCTGAGAAGCGTGAGCAGCGTGGACGAGCTGAT 
                   
               
               
                   
                 GAGCGTGCTGTACCCCGACTACTGGAAGATGTACAAGTGCCA 
                   
               
               
                   
                 GCTGAGAAAGGGCGGCTGGCAGCAGCCCACCCTGAACACCA 
                   
               
               
                   
                 GAACCGGCGACAGCGTGAAGTTCGCCGCCGCCCACTACAACA 
                   
               
               
                   
                 CCGAGATCCTGAAGAGCATCGACAACGAGTGGAGAAAGACC 
                   
               
               
                   
                 CAGTGCATGCCCAGAGAGGTGTGCATCGACGTGGGCAAGGA 
                   
               
               
                   
                 GTTCGGCGCCGCCACCAACACCTTCTTCAAGCCCCCCTGCGTG 
                   
               
               
                   
                 AGCGTGTACAGATGCGGCGGCTGCTGCAACAGCGAGGGCCTG 
                   
               
               
                   
                 CAGTGCATGAACACCAGCACCGGCTACCTGAGCAAGACCCTG 
                   
               
               
                   
                 TTCGAGATCACCGTGCCCCTGAGCCAGGGCCCCAAGCCCGTG 
                   
               
               
                   
                 ACCATCAGCTTCGCCAACCACACCAGCTGCAGATGCATGAGC 
                   
               
               
                   
                 AAGCTGGACGTGTACAGACAGGTGCACAGCATCATCAGAAG 
                   
               
               
                   
                 AAGCCTGCCCGCCACCCTGCCCCAGTGCCAGGCCGCCAACAA 
                   
               
               
                   
                 GACCTGCCCCACCAACTACGTGTGGAACAACTACATGTGCAG 
                   
               
               
                   
                 ATGCCTGGCCCAGCAGGACTTCATCTTCTACAGCAACGTGGA 
                   
               
               
                   
                 GGACGACAGCACCAACGGCTTCCACGACGTGTGCGGCCCCAA 
                   
               
               
                   
                 CAAGGAGCTGGACGAGGACACCTGCCAGTGCGTGTGCAAGG 
                   
               
               
                   
                 GCGGCCTGAGACCCAGCAGCTGCGGCCCCCACAAGGAGCTG 
                   
               
               
                   
                 GACAGAGACAGCTGCCAGTGCGTGTGCAAGAACAAGCTGTTC 
                   
               
               
                   
                 CCCAACAGCTGCGGCGCCAACAGAGAGTTCGACGAGAACAC 
                   
               
               
                   
                 CTGCCAGTGCGTGTGCAAGAGAACCTGCCCCAGAAACCAGCC 
                   
               
               
                   
                 CCTGAACCCCGGCAAGTGCGCCTGCGAGTGCACCGAGAACAC 
                   
               
               
                   
                 CCAGAAGTGCTTCCTGAAGGGCAAGAAGTTCCACCACCAGAC 
                   
               
               
                   
                 CTGCAGCTGCTACAGAAGACCCTGCGCCAACAGACTGAAGCA 
                   
               
               
                   
                 CTGCGACCCCGGCCTGAGCTTCAGCGAGGAGGTGTGCAGATG 
                   
               
               
                   
                 CGTGCCCAGCTACTGGAAGAGACCCCACCTGAAC 
                   
               
               
                   
               
               
                 mouse VEGF- 
                 ATGCACCTGCTGTGCTTCCTGAGCCTGGCCTGCAGCCTGCTGG 
                 14 
               
               
                 C full length 
                 CCGCCGCCCTGATCCCCAGCCCCAGAGAGGCCCCCGCCACCG 
                   
               
               
                 Cys152Ser 
                 TGGCCGCCTTCGAGAGCGGCCTGGGCTTCAGCGAGGCCGAGC 
                   
               
               
                 mutation 
                 CCGACGGCGGCGAGGTGAAGGCCTTCGAGGGCAAGGACCTG 
                   
               
               
                 codon 
                 GAGGAGCAGCTGAGAAGCGTGAGCAGCGTGGACGAGCTGAT 
                   
               
               
                 optimized 2 
                 GAGCGTGCTGTACCCCGACTACTGGAAGATGTACAAGTGCCA 
                   
               
               
                 (AGS) 
                 GCTGAGAAAGGGCGGCTGGCAGCAGCCCACCCTGAACACCA 
                   
               
               
                   
                 GAACCGGCGACAGCGTGAAGTTCGCCGCCGCCCACTACAACA 
                   
               
               
                   
                 CCGAGATCCTGAAGAGCATCGACAACGAGTGGAGAAAGACC 
                   
               
               
                   
                 CAGTGCATGCCCAGAGAGGTGTGCATCGACGTGGGCAAGGA 
                   
               
               
                   
                 GTTCGGCGCCGCCACCAACACCTTCTTCAAGCCCCCCTCCGTG 
                   
               
               
                   
                 AGCGTGTACAGATGCGGCGGCTGCTGCAACAGCGAGGGCCTG 
                   
               
               
                   
                 CAGTGCATGAACACCAGCACCGGCTACCTGAGCAAGACCCTG 
                   
               
               
                   
                 TTCGAGATCACCGTGCCCCTGAGCCAGGGCCCCAAGCCCGTG 
                   
               
               
                   
                 ACCATCAGCTTCGCCAACCACACCAGCTGCAGATGCATGAGC 
                   
               
               
                   
                 AAGCTGGACGTGTACAGACAGGTGCACAGCATCATCAGAAG 
                   
               
               
                   
                 AAGCCTGCCCGCCACCCTGCCCCAGTGCCAGGCCGCCAACAA 
                   
               
               
                   
                 GACCTGCCCCACCAACTACGTGTGGAACAACTACATGTGCAG 
                   
               
               
                   
                 ATGCCTGGCCCAGCAGGACTTCATCTTCTACAGCAACGTGGA 
                   
               
               
                   
                 GGACGACAGCACCAACGGCTTCCACGACGTGTGCGGCCCCAA 
                   
               
               
                   
                 CAAGGAGCTGGACGAGGACACCTGCCAGTGCGTGTGCAAGG 
                   
               
               
                   
                 GCGGCCTGAGACCCAGCAGCTGCGGCCCCCACAAGGAGCTG 
                   
               
               
                   
                 GACAGAGACAGCTGCCAGTGCGTGTGCAAGAACAAGCTGTTC 
                   
               
               
                   
                 CCCAACAGCTGCGGCGCCAACAGAGAGTTCGACGAGAACAC 
                   
               
               
                   
                 CTGCCAGTGCGTGTGCAAGAGAACCTGCCCCAGAAACCAGCC 
                   
               
               
                   
                 CCTGAACCCCGGCAAGTGCGCCTGCGAGTGCACCGAGAACAC 
                   
               
               
                   
                 CCAGAAGTGCTTCCTGAAGGGCAAGAAGTTCCACCACCAGAC 
                   
               
               
                   
                 CTGCAGCTGCTACAGAAGACCCTGCGCCAACAGACTGAAGCA 
                   
               
               
                   
                 CTGCGACCCCGGCCTGAGCTTCAGCGAGGAGGTGTGCAGATG 
                   
               
               
                   
                 CGTGCCCAGCTACTGGAAGAGACCCCACCTGAAC 
                   
               
               
                   
               
               
                 mouse VEGF- 
                 ATGCACCTGCTGTGCTTCCTGAGCCTGGCCTGCAGCCTGCTGG 
                 15 
               
               
                 C full length 
                 CCGCCGCCCTGATCCCCAGCCCCAGAGAGGCCCCCGCCACCG 
                   
               
               
                 Cys133Ala 
                 TGGCCGCCTTCGAGAGCGGCCTGGGCTTCAGCGAGGCCGAGC 
                   
               
               
                 mutation 
                 CCGACGGCGGCGAGGTGAAGGCCTTCGAGGGCAAGGACCTG 
                   
               
               
                 codon 
                 GAGGAGCAGCTGAGAAGCGTGAGCAGCGTGGACGAGCTGAT 
                   
               
               
                 optimized 2 
                 GAGCGTGCTGTACCCCGACTACTGGAAGATGTACAAGTGCCA 
                   
               
               
                 (AGS) 
                 GCTGAGAAAGGGCGGCTGGCAGCAGCCCACCCTGAACACCA 
                   
               
               
                   
                 GAACCGGCGACAGCGTGAAGTTCGCCGCCGCCCACTACAACA 
                   
               
               
                   
                 CCGAGATCCTGAAGAGCATCGACAACGAGTGGAGAAAGACC 
                   
               
               
                   
                 CAGTGCATGCCCAGAGAGGTGGCCATCGACGTGGGCAAGGA 
                   
               
               
                   
                 GTTCGGCGCCGCCACCAACACCTTCTTCAAGCCCCCCTGCGTG 
                   
               
               
                   
                 AGCGTGTACAGATGCGGCGGCTGCTGCAACAGCGAGGGCCTG 
                   
               
               
                   
                 CAGTGCATGAACACCAGCACCGGCTACCTGAGCAAGACCCTG 
                   
               
               
                   
                 TTCGAGATCACCGTGCCCCTGAGCCAGGGCCCCAAGCCCGTG 
                   
               
               
                   
                 ACCATCAGCTTCGCCAACCACACCAGCTGCAGATGCATGAGC 
                   
               
               
                   
                 AAGCTGGACGTGTACAGACAGGTGCACAGCATCATCAGAAG 
                   
               
               
                   
                 AAGCCTGCCCGCCACCCTGCCCCAGTGCCAGGCCGCCAACAA 
                   
               
               
                   
                 GACCTGCCCCACCAACTACGTGTGGAACAACTACATGTGCAG 
                   
               
               
                   
                 ATGCCTGGCCCAGCAGGACTTCATCTTCTACAGCAACGTGGA 
                   
               
               
                   
                 GGACGACAGCACCAACGGCTTCCACGACGTGTGCGGCCCCAA 
                   
               
               
                   
                 CAAGGAGCTGGACGAGGACACCTGCCAGTGCGTGTGCAAGG 
                   
               
               
                   
                 GCGGCCTGAGACCCAGCAGCTGCGGCCCCCACAAGGAGCTG 
                   
               
               
                   
                 GACAGAGACAGCTGCCAGTGCGTGTGCAAGAACAAGCTGTTC 
                   
               
               
                   
                 CCCAACAGCTGCGGCGCCAACAGAGAGTTCGACGAGAACAC 
                   
               
               
                   
                 CTGCCAGTGCGTGTGCAAGAGAACCTGCCCCAGAAACCAGCC 
                   
               
               
                   
                 CCTGAACCCCGGCAAGTGCGCCTGCGAGTGCACCGAGAACAC 
                   
               
               
                   
                 CCAGAAGTGCTTCCTGAAGGGCAAGAAGTTCCACCACCAGAC 
                   
               
               
                   
                 CTGCAGCTGCTACAGAAGACCCTGCGCCAACAGACTGAAGCA 
                   
               
               
                   
                 CTGCGACCCCGGCCTGAGCTTCAGCGAGGAGGTGTGCAGATG 
                   
               
               
                   
                 CGTGCCCAGCTACTGGAAGAGACCCCACCTGAAC 
                   
               
               
                   
               
               
                 mouse VEGF- 
                 GCCCACTACAACACCGAGATCCTGAAGAGCATCGACAACGA 
                 16 
               
               
                 C mature 
                 GTGGAGAAAGACCCAGTGCATGCCCAGAGAGGTGTGCATCG 
                   
               
               
                 (dNdC) wt 
                 ACGTGGGCAAGGAGTTCGGCGCCGCCACCAACACCTTCTTCA 
                   
               
               
                 codon 
                 AGCCCCCCTGCGTGAGCGTGTACAGATGCGGCGGCTGCTGCA 
                   
               
               
                 optimized 2 
                 ACAGCGAGGGCCTGCAGTGCATGAACACCAGCACCGGCTACC 
                   
               
               
                 (AGS) 
                 TGAGCAAGACCCTGTTCGAGATCACCGTGCCCCTGAGCCAGG 
                   
               
               
                   
                 GCCCCAAGCCCGTGACCATCAGCTTCGCCAACCACACCAGCT 
                   
               
               
                   
                 GCAGATGCATGAGCAAGCTGGACGTGTACAGACAGGTGCAC 
                   
               
               
                   
                 AGCATCATCAGAAGA 
                   
               
               
                   
               
               
                 mouse VEGF- 
                 GCCCACTACAACACCGAGATCCTGAAGAGCATCGACAACGA 
                 17 
               
               
                 C mature 
                 GTGGAGAAAGACCCAGTGCATGCCCAGAGAGGTGTGCATCG 
                   
               
               
                 (dNdC) 
                 ACGTGGGCAAGGAGTTCGGCGCCGCCACCAACACCTTCTTCA 
                   
               
               
                 Cys152Ser 
                 AGCCCCCCTCCGTGAGCGTGTACAGATGCGGCGGCTGCTGCA 
                   
               
               
                 mutation 
                 ACAGCGAGGGCCTGCAGTGCATGAACACCAGCACCGGCTACC 
                   
               
               
                 codon 
                 TGAGCAAGACCCTGTTCGAGATCACCGTGCCCCTGAGCCAGG 
                   
               
               
                 optimized 2 
                 GCCCCAAGCCCGTGACCATCAGCTTCGCCAACCACACCAGCT 
                   
               
               
                 (AGS) 
                 GCAGATGCATGAGCAAGCTGGACGTGTACAGACAGGTGCAC 
                   
               
               
                   
                 AGCATCATCAGAAGA 
                   
               
               
                   
               
               
                 mouse VEGF- 
                 GCCCACTACAACACCGAGATCCTGAAGAGCATCGACAACGA 
                 18 
               
               
                 C mature 
                 GTGGAGAAAGACCCAGTGCATGCCCAGAGAGGTGGCCATCG 
                   
               
               
                 (dNdC) 
                 ACGTGGGCAAGGAGTTCGGCGCCGCCACCAACACCTTCTTCA 
                   
               
               
                 Cys133Ala 
                 AGCCCCCCTGCGTGAGCGTGTACAGATGCGGCGGCTGCTGCA 
                   
               
               
                 mutation 
                 ACAGCGAGGGCCTGCAGTGCATGAACACCAGCACCGGCTACC 
                   
               
               
                 codon 
                 TGAGCAAGACCCTGTTCGAGATCACCGTGCCCCTGAGCCAGG 
                   
               
               
                 optimized 2 
                 GCCCCAAGCCCGTGACCATCAGCTTCGCCAACCACACCAGCT 
                   
               
               
                 (AGS) 
                 GCAGATGCATGAGCAAGCTGGACGTGTACAGACAGGTGCAC 
                   
               
               
                   
                 AGCATCATCAGAAGA 
                   
               
               
                   
               
               
                 mouse VEGF- 
                 MHLLCFLSLACSLLAAALIPSPREAPATVAAFESGLGFSEAEPDG 
                 19 
               
               
                 C full length 
                 GEVKAFEGKDLEEQLRSVSSVDELMSVLYPDYWKMYKCQLRK 
                   
               
               
                 wt 
                 GGWQQPTLNTRTGDSVKFAAAHYNTEILKSIDNEWRKTQCMPR 
                   
               
               
                   
                 EVCIDVGKEFGAATNTFFKPPCVSVYRCGGCCNSEGLQCMNTST 
                   
               
               
                   
                 GYLSKTLFEITVPLSQGPKPVTISFANHTSCRCMSKLDVYRQVHS 
                   
               
               
                   
                 IIRRSLPATLPQCQAANKTCPTNYVWNNYMCRCLAQQDFIFYSN 
                   
               
               
                   
                 VEDDSTNGFHDVCGPNKELDEDTCQCVCKGGLRPSSCGPHKEL 
                   
               
               
                   
                 DRDSCQCVCKNKLFPNSCGANREFDENTCQCVCKRTCPRNQPL 
                   
               
               
                   
                 NPGKCACECTENTQKCFLKGKKFHHQTCSCYRRPCANRLKHCD 
                   
               
               
                   
                 PGLSFSEEVCRCVPSYWKRPHLN 
                   
               
               
                   
               
               
                 mouse VEGF- 
                 MHLLCFLSLACSLLAAALIPSPREAPATVAAFESGLGFSEAEPDG 
                 20 
               
               
                 C full length 
                 GEVKAFEGKDLEEQLRSVSSVDELMSVLYPDYWKMYKCQLRK 
                   
               
               
                 Cys152Ser 
                 GGWQQPTLNTRTGDSVKFAAAHYNTEILKSIDNEWRKTQCMPR 
                   
               
               
                 mutation 
                 EVCIDVGKEFGAATNTFFKPPSVSVYRCGGCCNSEGLQCMNTST 
                   
               
               
                   
                 GYLSKTLFEITVPLSQGPKPVTISFANHTSCRCMSKLDVYRQVHS 
                   
               
               
                   
                 IIRRSLPATLPQCQAANKTCPTNYVWNNYMCRCLAQQDFIFYSN 
                   
               
               
                   
                 VEDDSTNGFHDVCGPNKELDEDTCQCVCKGGLRPSSCGPHKEL 
                   
               
               
                   
                 DRDSCQCVCKNKLFPNSCGANREFDENTCQCVCKRTCPRNQPL 
                   
               
               
                   
                 NPGKCACECTENTQKCFLKGKKFHHQTCSCYRRPCANRLKHCD 
                   
               
               
                   
                 PGLSFSEEVCRCVPSYWKRPHLN 
                   
               
               
                   
               
               
                 mouse VEGF- 
                 MHLLCFLSLACSLLAAALIPSPREAPATVAAFESGLGFSEAEPDG 
                 21 
               
               
                 C full length 
                 GEVKAFEGKDLEEQLRSVSSVDELMSVLYPDYWKMYKCQLRK 
                   
               
               
                 Cys133Ala 
                 GGWQQPTLNTRTGDSVKFAAAHYNTEILKSIDNEWRKTQCMPR 
                   
               
               
                 mutation 
                 EVAIDVGKEFGAATNTFFKPPCVSVYRCGGCCNSEGLQCMNTST 
                   
               
               
                   
                 GYLSKTLFEITVPLSQGPKPVTISFANHTSCRCMSKLDVYRQVHS 
                   
               
               
                   
                 IIRRSLPATLPQCQAANKTCPTNYVWNNYMCRCLAQQDFIFYSN 
                   
               
               
                   
                 VEDDSTNGFHDVCGPNKELDEDTCQCVCKGGLRPSSCGPHKEL 
                   
               
               
                   
                 DRDSCQCVCKNKLFPNSCGANREFDENTCQCVCKRTCPRNQPL 
                   
               
               
                   
                 NPGKCACECTENTQKCFLKGKKFHHQTCSCYRRPCANRLKHCD 
                   
               
               
                   
                 PGLSFSEEVCRCVPSYWKRPHLN 
                   
               
               
                   
               
               
                 mouse VEGF- 
                 AHYNTEILKSIDNEWRKTQCMPREVCIDVGKEFGAATNTFFKPP 
                 22 
               
               
                 C mature 
                 CVSVYRCGGCCNSEGLQCMNTSTGYLSKTLFEITVPLSQGPKPV 
                   
               
               
                 (dNdC) wt 
                 TISFANHTSCRCMSKLDVYRQVHSIIRR 
                   
               
               
                   
               
               
                 mouse VEGF- 
                 AHYNTEILKSIDNEWRKTQCMPREVCIDVGKEFGAATNTFFKPP 
                 23 
               
               
                 C mature 
                 SVSVYRCGGCCNSEGLQCMNTSTGYLSKTLFEITVPLSQGPKPV 
                   
               
               
                 (dNdC) 
                 TISFANHTSCRCMSKLDVYRQVHSIIRR 
                   
               
               
                 Cys152Ser 
                   
                   
               
               
                   
               
               
                 mouse VEGF- 
                 AHYNTEILKSIDNEWRKTQCMPREVAIDVGKEFGAATNTFFKPP 
                 24 
               
               
                 C mature 
                 CVSVYRCGGCCNSEGLQCMNTSTGYLSKTLFEITVPLSQGPKPV 
                   
               
               
                 (dNdC) 
                 TISFANHTSCRCMSKLDVYRQVHSIIRR 
                   
               
               
                 Cys133Ala 
                   
                   
               
               
                   
               
               
                 Signal peptide 
                 ATGCGGGTGCCCGCCCAGCTGCTGGGCCTGCTCCTGCTCTGG 
                 25 
               
               
                 IgG light 
                 CTGCCAGGCGCTAGATGT 
                   
               
               
                 chain 
                   
                   
               
               
                   
               
               
                 Signal peptide 
                 MRVPAQLLGLLLLWLPGARC 
                 26 
               
               
                 IgG light 
                   
                   
               
               
                 chain 
                   
                   
               
               
                   
               
               
                 Signal peptide 
                 ATGGGCGTGAAGGTGCTGTTCGCCCTGATCTGCATCGCCGTG 
                 27 
               
               
                 
                   Gaussia 
                 
                 GCCGAGGCC 
                   
               
               
                 
                   luciferase 
                 
                   
                   
               
               
                   
               
               
                 Signal peptide 
                 MGVKVLFALICIAVAEA 
                 28 
               
               
                 
                   Gaussia 
                 
                   
                   
               
               
                 
                   luciferase 
                 
                   
                   
               
               
                   
               
               
                 human VEGF- 
                 ATGCACTTGCTGGGCTTCTTCTCTGTGGCGTGTTCTCTGCTCG 
                 29 
               
               
                 C full length 
                 CCGCTGCGCTGCTCCCGGGTCCTCGCGAGGCGCCCGCCGCCG 
                   
               
               
                 wt native 
                 CCGCCGCCTTCGAGTCCGGACTCGACCTCTCGGACGCGGAGC 
                   
               
               
                   
                 CCGACGCGGGCGAGGCCACGGCTTATGCAAGCAAAGATCTG 
                   
               
               
                   
                 GAGGAGCAGTTACGGTCTGTGTCCAGTGTAGATGAACTCATG 
                   
               
               
                   
                 ACTGTACTCTACCCAGAATATTGGAAAATGTACAAGTGTCAG 
                   
               
               
                   
                 CTAAGGAAAGGAGGCTGGCAACATAACAGAGAACAGGCCAA 
                   
               
               
                   
                 CCTCAACTCAAGGACAGAAGAGACTATAAAATTTGCTGCAGC 
                   
               
               
                   
                 ACATTATAATACAGAGATCTTGAAAAGTATTGATAATGAGTG 
                   
               
               
                   
                 GAGAAAGACTCAATGCATGCCACGGGAGGTGTGTATAGATGT 
                   
               
               
                   
                 GGGGAAGGAGTTTGGAGTCGCGACAAACACCTTCTTTAAACC 
                   
               
               
                   
                 TCCATGTGTGTCCGTCTACAGATGTGGGGGTTGCTGCAATAGT 
                   
               
               
                   
                 GAGGGGCTGCAGTGCATGAACACCAGCACGAGCTACCTCAGC 
                   
               
               
                   
                 AAGACGTTATTTGAAATTACAGTGCCTCTCTCTCAAGGCCCCA 
                   
               
               
                   
                 AACCAGTAACAATCAGTTTTGCCAATCACACTTCCTGCCGAT 
                   
               
               
                   
                 GCATGTCTAAACTGGATGTTTACAGACAAGTTCATTCCATTAT 
                   
               
               
                   
                 TAGACGTTCCCTGCCAGCAACACTACCACAGTGTCAGGCAGC 
                   
               
               
                   
                 GAACAAGACCTGCCCCACCAATTACATGTGGAATAATCACAT 
                   
               
               
                   
                 CTGCAGATGCCTGGCTCAGGAAGATTTTATGTTTTCCTCGGAT 
                   
               
               
                   
                 GCTGGAGATGACTCAACAGATGGATTCCATGACATCTGTGGA 
                   
               
               
                   
                 CCAAACAAGGAGCTGGATGAAGAGACCTGTCAGTGTGTCTGC 
                   
               
               
                   
                 AGAGCGGGGCTTCGGCCTGCCAGCTGTGGACCCCACAAAGAA 
                   
               
               
                   
                 CTAGACAGAAACTCATGCCAGTGTGTCTGTAAAAACAAACTC 
                   
               
               
                   
                 TTCCCCAGCCAATGTGGGGCCAACCGAGAATTTGATGAAAAC 
                   
               
               
                   
                 ACATGCCAGTGTGTATGTAAAAGAACCTGCCCCAGAAATCAA 
                   
               
               
                   
                 CCCCTAAATCCTGGAAAATGTGCCTGTGAATGTACAGAAAGT 
                   
               
               
                   
                 CCACAGAAATGCTTGTTAAAAGGAAAGAAGTTCCACCACCAA 
                   
               
               
                   
                 ACATGCAGCTGTTACAGACGGCCATGTACGAACCGCCAGAAG 
                   
               
               
                   
                 GCTTGTGAGCCAGGATTTTCATATAGTGAAGAAGTGTGTCGT 
                   
               
               
                   
                 TGTGTCCCTTCATATTGGAAAAGACCACAAATGAGCTAA 
                   
               
               
                   
               
               
                 human VEGF- 
                 ATGCACTTGCTGGGCTTCTTCTCTGTGGCGTGTTCTCTGCTCG 
                 30 
               
               
                 C full length 
                 CCGCTGCGCTGCTCCCGGGTCCTCGCGAGGCGCCCGCCGCCG 
                   
               
               
                 Cys156Ser 
                 CCGCCGCCTTCGAGTCCGGACTCGACCTCTCGGACGCGGAGC 
                   
               
               
                 mutation 
                 CCGACGCGGGCGAGGCCACGGCTTATGCAAGCAAAGATCTG 
                   
               
               
                 native 
                 GAGGAGCAGTTACGGTCTGTGTCCAGTGTAGATGAACTCATG 
                   
               
               
                   
                 ACTGTACTCTACCCAGAATATTGGAAAATGTACAAGTGTCAG 
                   
               
               
                   
                 CTAAGGAAAGGAGGCTGGCAACATAACAGAGAACAGGCCAA 
                   
               
               
                   
                 CCTCAACTCAAGGACAGAAGAGACTATAAAATTTGCTGCAGC 
                   
               
               
                   
                 ACATTATAATACAGAGATCTTGAAAAGTATTGATAATGAGTG 
                   
               
               
                   
                 GAGAAAGACTCAATGCATGCCACGGGAGGTGTGTATAGATGT 
                   
               
               
                   
                 GGGGAAGGAGTTTGGAGTCGCGACAAACACCTTCTTTAAACC 
                   
               
               
                   
                 TCCATCTGTGTCCGTCTACAGATGTGGGGGTTGCTGCAATAGT 
                   
               
               
                   
                 GAGGGGCTGCAGTGCATGAACACCAGCACGAGCTACCTCAGC 
                   
               
               
                   
                 AAGACGTTATTTGAAATTACAGTGCCTCTCTCTCAAGGCCCCA 
                   
               
               
                   
                 AACCAGTAACAATCAGTTTTGCCAATCACACTTCCTGCCGAT 
                   
               
               
                   
                 GCATGTCTAAACTGGATGTTTACAGACAAGTTCATTCCATTAT 
                   
               
               
                   
                 TAGACGTTCCCTGCCAGCAACACTACCACAGTGTCAGGCAGC 
                   
               
               
                   
                 GAACAAGACCTGCCCCACCAATTACATGTGGAATAATCACAT 
                   
               
               
                   
                 CTGCAGATGCCTGGCTCAGGAAGATTTTATGTTTTCCTCGGAT 
                   
               
               
                   
                 GCTGGAGATGACTCAACAGATGGATTCCATGACATCTGTGGA 
                   
               
               
                   
                 CCAAACAAGGAGCTGGATGAAGAGACCTGTCAGTGTGTCTGC 
                   
               
               
                   
                 AGAGCGGGGCTTCGGCCTGCCAGCTGTGGACCCCACAAAGAA 
                   
               
               
                   
                 CTAGACAGAAACTCATGCCAGTGTGTCTGTAAAAACAAACTC 
                   
               
               
                   
                 TTCCCCAGCCAATGTGGGGCCAACCGAGAATTTGATGAAAAC 
                   
               
               
                   
                 ACATGCCAGTGTGTATGTAAAAGAACCTGCCCCAGAAATCAA 
                   
               
               
                   
                 CCCCTAAATCCTGGAAAATGTGCCTGTGAATGTACAGAAAGT 
                   
               
               
                   
                 CCACAGAAATGCTTGTTAAAAGGAAAGAAGTTCCACCACCAA 
                   
               
               
                   
                 ACATGCAGCTGTTACAGACGGCCATGTACGAACCGCCAGAAG 
                   
               
               
                   
                 GCTTGTGAGCCAGGATTTTCATATAGTGAAGAAGTGTGTCGT 
                   
               
               
                   
                 TGTGTCCCTTCATATTGGAAAAGACCACAAATGAGCTAA 
                   
               
               
                   
               
               
                 human VEGF- 
                 ATGCACTTGCTGGGCTTCTTCTCTGTGGCGTGTTCTCTGCTCG 
                 31 
               
               
                 C full length 
                 CCGCTGCGCTGCTCCCGGGTCCTCGCGAGGCGCCCGCCGCCG 
                   
               
               
                 Cys137A1a 
                 CCGCCGCCTTCGAGTCCGGACTCGACCTCTCGGACGCGGAGC 
                   
               
               
                 mutation 
                 CCGACGCGGGCGAGGCCACGGCTTATGCAAGCAAAGATCTG 
                   
               
               
                 native 
                 GAGGAGCAGTTACGGTCTGTGTCCAGTGTAGATGAACTCATG 
                   
               
               
                   
                 ACTGTACTCTACCCAGAATATTGGAAAATGTACAAGTGTCAG 
                   
               
               
                   
                 CTAAGGAAAGGAGGCTGGCAACATAACAGAGAACAGGCCAA 
                   
               
               
                   
                 CCTCAACTCAAGGACAGAAGAGACTATAAAATTTGCTGCAGC 
                   
               
               
                   
                 ACATTATAATACAGAGATCTTGAAAAGTATTGATAATGAGTG 
                   
               
               
                   
                 GAGAAAGACTCAATGCATGCCACGGGAGGTGGCTATAGATGT 
                   
               
               
                   
                 GGGGAAGGAGTTTGGAGTCGCGACAAACACCTTCTTTAAACC 
                   
               
               
                   
                 TCCATGTGTGTCCGTCTACAGATGTGGGGGTTGCTGCAATAGT 
                   
               
               
                   
                 GAGGGGCTGCAGTGCATGAACACCAGCACGAGCTACCTCAGC 
                   
               
               
                   
                 AAGACGTTATTTGAAATTACAGTGCCTCTCTCTCAAGGCCCCA 
                   
               
               
                   
                 AACCAGTAACAATCAGTTTTGCCAATCACACTTCCTGCCGAT 
                   
               
               
                   
                 GCATGTCTAAACTGGATGTTTACAGACAAGTTCATTCCATTAT 
                   
               
               
                   
                 TAGACGTTCCCTGCCAGCAACACTACCACAGTGTCAGGCAGC 
                   
               
               
                   
                 GAACAAGACCTGCCCCACCAATTACATGTGGAATAATCACAT 
                   
               
               
                   
                 CTGCAGATGCCTGGCTCAGGAAGATTTTATGTTTTCCTCGGAT 
                   
               
               
                   
                 GCTGGAGATGACTCAACAGATGGATTCCATGACATCTGTGGA 
                   
               
               
                   
                 CCAAACAAGGAGCTGGATGAAGAGACCTGTCAGTGTGTCTGC 
                   
               
               
                   
                 AGAGCGGGGCTTCGGCCTGCCAGCTGTGGACCCCACAAAGAA 
                   
               
               
                   
                 CTAGACAGAAACTCATGCCAGTGTGTCTGTAAAAACAAACTC 
                   
               
               
                   
                 TTCCCCAGCCAATGTGGGGCCAACCGAGAATTTGATGAAAAC 
                   
               
               
                   
                 ACATGCCAGTGTGTATGTAAAAGAACCTGCCCCAGAAATCAA 
                   
               
               
                   
                 CCCCTAAATCCTGGAAAATGTGCCTGTGAATGTACAGAAAGT 
                   
               
               
                   
                 CCACAGAAATGCTTGTTAAAAGGAAAGAAGTTCCACCACCAA 
                   
               
               
                   
                 ACATGCAGCTGTTACAGACGGCCATGTACGAACCGCCAGAAG 
                   
               
               
                   
                 GCTTGTGAGCCAGGATTTTCATATAGTGAAGAAGTGTGTCGT 
                   
               
               
                   
                 TGTGTCCCTTCATATTGGAAAAGACCACAAATGAGCTAA 
                   
               
               
                   
               
               
                 human VEGF- 
                 GCACATTATAATACAGAGATCTTGAAAAGTATTGATAATGAG 
                 32 
               
               
                 C mature 
                 TGGAGAAAGACTCAATGCATGCCACGGGAGGTGTGTATAGAT 
                   
               
               
                 (dNdC) wt 
                 GTGGGGAAGGAGTTTGGAGTCGCGACAAACACCTTCTTTAAA 
                   
               
               
                 native 
                 CCTCCATGTGTGTCCGTCTACAGATGTGGGGGTTGCTGCAATA 
                   
               
               
                   
                 GTGAGGGGCTGCAGTGCATGAACACCAGCACGAGCTACCTCA 
                   
               
               
                   
                 GCAAGACGTTATTTGAAATTACAGTGCCTCTCTCTCAAGGCCC 
                   
               
               
                   
                 CAAACCAGTAACAATCAGTTTTGCCAATCACACTTCCTGCCG 
                   
               
               
                   
                 ATGCATGTCTAAACTGGATGTTTACAGACAAGTTCATTCCATT 
                   
               
               
                   
                 ATTAGACGT 
                   
               
               
                   
               
               
                 human VEGF- 
                 GCACATTATAATACAGAGATCTTGAAAAGTATTGATAATGAG 
                 33 
               
               
                 C mature 
                 TGGAGAAAGACTCAATGCATGCCACGGGAGGTGTGTATAGAT 
                   
               
               
                 (dNdC) 
                 GTGGGGAAGGAGTTTGGAGTCGCGACAAACACCTTCTTTAAA 
                   
               
               
                 Cys156Ser 
                 CCTCCATCTGTGTCCGTCTACAGATGTGGGGGTTGCTGCAATA 
                   
               
               
                 mutation 
                 GTGAGGGGCTGCAGTGCATGAACACCAGCACGAGCTACCTCA 
                   
               
               
                 native 
                 GCAAGACGTTATTTGAAATTACAGTGCCTCTCTCTCAAGGCCC 
                   
               
               
                   
                 CAAACCAGTAACAATCAGTTTTGCCAATCACACTTCCTGCCG 
                   
               
               
                   
                 ATGCATGTCTAAACTGGATGTTTACAGACAAGTTCATTCCATT 
                   
               
               
                   
                 ATTAGACGT 
                   
               
               
                   
               
               
                 human VEGF- 
                 GCACATTATAATACAGAGATCTTGAAAAGTATTGATAATGAG 
                 34 
               
               
                 C mature 
                 TGGAGAAAGACTCAATGCATGCCACGGGAGGTGGCTATAGAT 
                   
               
               
                 (dNdC) 
                 GTGGGGAAGGAGTTTGGAGTCGCGACAAACACCTTCTTTAAA 
                   
               
               
                 Cys137A1a 
                 CCTCCATGTGTGTCCGTCTACAGATGTGGGGGTTGCTGCAATA 
                   
               
               
                 mutation 
                 GTGAGGGGCTGCAGTGCATGAACACCAGCACGAGCTACCTCA 
                   
               
               
                 native 
                 GCAAGACGTTATTTGAAATTACAGTGCCTCTCTCTCAAGGCCC 
                   
               
               
                   
                 CAAACCAGTAACAATCAGTTTTGCCAATCACACTTCCTGCCG 
                   
               
               
                   
                 ATGCATGTCTAAACTGGATGTTTACAGACAAGTTCATTCCATT 
                   
               
               
                   
                 ATTAGACGT 
                   
               
               
                   
               
               
                 human VEGF- 
                 ATGCACCTGCTGGGCTTCTTCAGCGTGGCCTGCAGCCTGCTGG 
                 35 
               
               
                 C full length 
                 CCGCCGCCCTGCTGCCCGGCCCCAGAGAGGCCCCCGCCGCCG 
                   
               
               
                 wt codon 
                 CCGCCGCCTTCGAGAGCGGCCTGGACCTGAGCGACGCCGAGC 
                   
               
               
                 optimized 2 
                 CCGACGCCGGCGAGGCCACCGCCTACGCCAGCAAGGACCTG 
                   
               
               
                 (AGS) 
                 GAGGAGCAGCTGAGAAGCGTGAGCAGCGTGGACGAGCTGAT 
                   
               
               
                   
                 GACCGTGCTGTACCCCGAGTACTGGAAGATGTACAAGTGCCA 
                   
               
               
                   
                 GCTGAGAAAGGGCGGCTGGCAGCACAACAGAGAGCAGGCCA 
                   
               
               
                   
                 ACCTGAACAGCAGAACCGAGGAGACCATCAAGTTCGCCGCC 
                   
               
               
                   
                 GCCCACTACAACACCGAGATCCTGAAGAGCATCGACAACGA 
                   
               
               
                   
                 GTGGAGAAAGACCCAGTGCATGCCCAGAGAGGTGTGCATCG 
                   
               
               
                   
                 ACGTGGGCAAGGAGTTCGGCGTGGCCACCAACACCTTCTTCA 
                   
               
               
                   
                 AGCCCCCCTGCGTGAGCGTGTACAGATGCGGCGGCTGCTGCA 
                   
               
               
                   
                 ACAGCGAGGGCCTGCAGTGCATGAACACCAGCACCAGCTACC 
                   
               
               
                   
                 TGAGCAAGACCCTGTTCGAGATCACCGTGCCCCTGAGCCAGG 
                   
               
               
                   
                 GCCCCAAGCCCGTGACCATCAGCTTCGCCAACCACACCAGCT 
                   
               
               
                   
                 GCAGATGCATGAGCAAGCTGGACGTGTACAGACAGGTGCAC 
                   
               
               
                   
                 AGCATCATCAGAAGAAGCCTGCCCGCCACCCTGCCCCAGTGC 
                   
               
               
                   
                 CAGGCCGCCAACAAGACCTGCCCCACCAACTACATGTGGAAC 
                   
               
               
                   
                 AACCACATCTGCAGATGCCTGGCCCAGGAGGACTTCATGTTC 
                   
               
               
                   
                 AGCAGCGACGCCGGCGACGACAGCACCGACGGCTTCCACGA 
                   
               
               
                   
                 CATCTGCGGCCCCAACAAGGAGCTGGACGAGGAGACCTGCC 
                   
               
               
                   
                 AGTGCGTGTGCAGAGCCGGCCTGAGACCCGCCAGCTGCGGCC 
                   
               
               
                   
                 CCCACAAGGAGCTGGACAGAAACAGCTGCCAGTGCGTGTGC 
                   
               
               
                   
                 AAGAACAAGCTGTTCCCCAGCCAGTGCGGCGCCAACAGAGA 
                   
               
               
                   
                 GTTCGACGAGAACACCTGCCAGTGCGTGTGCAAGAGAACCTG 
                   
               
               
                   
                 CCCCAGAAACCAGCCCCTGAACCCCGGCAAGTGCGCCTGCGA 
                   
               
               
                   
                 GTGCACCGAGAGCCCCCAGAAGTGCCTGCTGAAGGGCAAGA 
                   
               
               
                   
                 AGTTCCACCACCAGACCTGCAGCTGCTACAGAAGACCCTGCA 
                   
               
               
                   
                 CCAACAGACAGAAGGCCTGCGAGCCCGGCTTCAGCTACAGCG 
                   
               
               
                   
                 AGGAGGTGTGCAGATGCGTGCCCAGCTACTGGAAGAGACCCC 
                   
               
               
                   
                 AGATGAGCTGA 
                   
               
               
                   
               
               
                 human VEGF- 
                 ATGCACCTGCTGGGCTTCTTCAGCGTGGCCTGCAGCCTGCTGG 
                 36 
               
               
                 C full length 
                 CCGCCGCCCTGCTGCCCGGCCCCAGAGAGGCCCCCGCCGCCG 
                   
               
               
                 Cys156Ser 
                 CCGCCGCCTTCGAGAGCGGCCTGGACCTGAGCGACGCCGAGC 
                   
               
               
                 mutation 
                 CCGACGCCGGCGAGGCCACCGCCTACGCCAGCAAGGACCTG 
                   
               
               
                 codon 
                 GAGGAGCAGCTGAGAAGCGTGAGCAGCGTGGACGAGCTGAT 
                   
               
               
                 optimized 2 
                 GACCGTGCTGTACCCCGAGTACTGGAAGATGTACAAGTGCCA 
                   
               
               
                 (AGS) 
                 GCTGAGAAAGGGCGGCTGGCAGCACAACAGAGAGCAGGCCA 
                   
               
               
                   
                 ACCTGAACAGCAGAACCGAGGAGACCATCAAGTTCGCCGCC 
                   
               
               
                   
                 GCCCACTACAACACCGAGATCCTGAAGAGCATCGACAACGA 
                   
               
               
                   
                 GTGGAGAAAGACCCAGTGCATGCCCAGAGAGGTGTGCATCG 
                   
               
               
                   
                 ACGTGGGCAAGGAGTTCGGCGTGGCCACCAACACCTTCTTCA 
                   
               
               
                   
                 AGCCCCCCTCCGTGAGCGTGTACAGATGCGGCGGCTGCTGCA 
                   
               
               
                   
                 ACAGCGAGGGCCTGCAGTGCATGAACACCAGCACCAGCTACC 
                   
               
               
                   
                 TGAGCAAGACCCTGTTCGAGATCACCGTGCCCCTGAGCCAGG 
                   
               
               
                   
                 GCCCCAAGCCCGTGACCATCAGCTTCGCCAACCACACCAGCT 
                   
               
               
                   
                 GCAGATGCATGAGCAAGCTGGACGTGTACAGACAGGTGCAC 
                   
               
               
                   
                 AGCATCATCAGAAGAAGCCTGCCCGCCACCCTGCCCCAGTGC 
                   
               
               
                   
                 CAGGCCGCCAACAAGACCTGCCCCACCAACTACATGTGGAAC 
                   
               
               
                   
                 AACCACATCTGCAGATGCCTGGCCCAGGAGGACTTCATGTTC 
                   
               
               
                   
                 AGCAGCGACGCCGGCGACGACAGCACCGACGGCTTCCACGA 
                   
               
               
                   
                 CATCTGCGGCCCCAACAAGGAGCTGGACGAGGAGACCTGCC 
                   
               
               
                   
                 AGTGCGTGTGCAGAGCCGGCCTGAGACCCGCCAGCTGCGGCC 
                   
               
               
                   
                 CCCACAAGGAGCTGGACAGAAACAGCTGCCAGTGCGTGTGC 
                   
               
               
                   
                 AAGAACAAGCTGTTCCCCAGCCAGTGCGGCGCCAACAGAGA 
                   
               
               
                   
                 GTTCGACGAGAACACCTGCCAGTGCGTGTGCAAGAGAACCTG 
                   
               
               
                   
                 CCCCAGAAACCAGCCCCTGAACCCCGGCAAGTGCGCCTGCGA 
                   
               
               
                   
                 GTGCACCGAGAGCCCCCAGAAGTGCCTGCTGAAGGGCAAGA 
                   
               
               
                   
                 AGTTCCACCACCAGACCTGCAGCTGCTACAGAAGACCCTGCA 
                   
               
               
                   
                 CCAACAGACAGAAGGCCTGCGAGCCCGGCTTCAGCTACAGCG 
                   
               
               
                   
                 AGGAGGTGTGCAGATGCGTGCCCAGCTACTGGAAGAGACCCC 
                   
               
               
                   
                 AGATGAGCTGA 
                   
               
               
                   
               
               
                 human VEGF- 
                 ATGCACCTGCTGGGCTTCTTCAGCGTGGCCTGCAGCCTGCTGG 
                 37 
               
               
                 C full length 
                 CCGCCGCCCTGCTGCCCGGCCCCAGAGAGGCCCCCGCCGCCG 
                   
               
               
                 Cys137A1a 
                 CCGCCGCCTTCGAGAGCGGCCTGGACCTGAGCGACGCCGAGC 
                   
               
               
                 mutation 
                 CCGACGCCGGCGAGGCCACCGCCTACGCCAGCAAGGACCTG 
                   
               
               
                 codon 
                 GAGGAGCAGCTGAGAAGCGTGAGCAGCGTGGACGAGCTGAT 
                   
               
               
                 optimized 2 
                 GACCGTGCTGTACCCCGAGTACTGGAAGATGTACAAGTGCCA 
                   
               
               
                 (AGS) 
                 GCTGAGAAAGGGCGGCTGGCAGCACAACAGAGAGCAGGCCA 
                   
               
               
                   
                 ACCTGAACAGCAGAACCGAGGAGACCATCAAGTTCGCCGCC 
                   
               
               
                   
                 GCCCACTACAACACCGAGATCCTGAAGAGCATCGACAACGA 
                   
               
               
                   
                 GTGGAGAAAGACCCAGTGCATGCCCAGAGAGGTGGCCATCG 
                   
               
               
                   
                 ACGTGGGCAAGGAGTTCGGCGTGGCCACCAACACCTTCTTCA 
                   
               
               
                   
                 AGCCCCCCTGCGTGAGCGTGTACAGATGCGGCGGCTGCTGCA 
                   
               
               
                   
                 ACAGCGAGGGCCTGCAGTGCATGAACACCAGCACCAGCTACC 
                   
               
               
                   
                 TGAGCAAGACCCTGTTCGAGATCACCGTGCCCCTGAGCCAGG 
                   
               
               
                   
                 GCCCCAAGCCCGTGACCATCAGCTTCGCCAACCACACCAGCT 
                   
               
               
                   
                 GCAGATGCATGAGCAAGCTGGACGTGTACAGACAGGTGCAC 
                   
               
               
                   
                 AGCATCATCAGAAGAAGCCTGCCCGCCACCCTGCCCCAGTGC 
                   
               
               
                   
                 CAGGCCGCCAACAAGACCTGCCCCACCAACTACATGTGGAAC 
                   
               
               
                   
                 AACCACATCTGCAGATGCCTGGCCCAGGAGGACTTCATGTTC 
                   
               
               
                   
                 AGCAGCGACGCCGGCGACGACAGCACCGACGGCTTCCACGA 
                   
               
               
                   
                 CATCTGCGGCCCCAACAAGGAGCTGGACGAGGAGACCTGCC 
                   
               
               
                   
                 AGTGCGTGTGCAGAGCCGGCCTGAGACCCGCCAGCTGCGGCC 
                   
               
               
                   
                 CCCACAAGGAGCTGGACAGAAACAGCTGCCAGTGCGTGTGC 
                   
               
               
                   
                 AAGAACAAGCTGTTCCCCAGCCAGTGCGGCGCCAACAGAGA 
                   
               
               
                   
                 GTTCGACGAGAACACCTGCCAGTGCGTGTGCAAGAGAACCTG 
                   
               
               
                   
                 CCCCAGAAACCAGCCCCTGAACCCCGGCAAGTGCGCCTGCGA 
                   
               
               
                   
                 GTGCACCGAGAGCCCCCAGAAGTGCCTGCTGAAGGGCAAGA 
                   
               
               
                   
                 AGTTCCACCACCAGACCTGCAGCTGCTACAGAAGACCCTGCA 
                   
               
               
                   
                 CCAACAGACAGAAGGCCTGCGAGCCCGGCTTCAGCTACAGCG 
                   
               
               
                   
                 AGGAGGTGTGCAGATGCGTGCCCAGCTACTGGAAGAGACCCC 
                   
               
               
                   
                 AGATGAGCTGA 
                   
               
               
                   
               
               
                 human VEGF- 
                 GCCCACTACAACACCGAGATCCTGAAGAGCATCGACAACGA 
                 38 
               
               
                 C mature 
                 GTGGAGAAAGACCCAGTGCATGCCCAGAGAGGTGTGCATCG 
                   
               
               
                 (dNdC) wt 
                 ACGTGGGCAAGGAGTTCGGCGTGGCCACCAACACCTTCTTCA 
                   
               
               
                 codon 
                 AGCCCCCCTGCGTGAGCGTGTACAGATGCGGCGGCTGCTGCA 
                   
               
               
                 optimized 2 
                 ACAGCGAGGGCCTGCAGTGCATGAACACCAGCACCAGCTACC 
                   
               
               
                 (AGS) 
                 TGAGCAAGACCCTGTTCGAGATCACCGTGCCCCTGAGCCAGG 
                   
               
               
                   
                 GCCCCAAGCCCGTGACCATCAGCTTCGCCAACCACACCAGCT 
                   
               
               
                   
                 GCAGATGCATGAGCAAGCTGGACGTGTACAGACAGGTGCAC 
                   
               
               
                   
                 AGCATCATCAGAAGA 
                   
               
               
                   
               
               
                 human VEGF- 
                 GCCCACTACAACACCGAGATCCTGAAGAGCATCGACAACGA 
                 39 
               
               
                 C mature 
                 GTGGAGAAAGACCCAGTGCATGCCCAGAGAGGTGTGCATCG 
                   
               
               
                 (dNdC) 
                 ACGTGGGCAAGGAGTTCGGCGTGGCCACCAACACCTTCTTCA 
                   
               
               
                 Cys156Ser 
                 AGCCCCCCTCCGTGAGCGTGTACAGATGCGGCGGCTGCTGCA 
                   
               
               
                 mutation 
                 ACAGCGAGGGCCTGCAGTGCATGAACACCAGCACCAGCTACC 
                   
               
               
                 codon 
                 TGAGCAAGACCCTGTTCGAGATCACCGTGCCCCTGAGCCAGG 
                   
               
               
                 optimized 2 
                 GCCCCAAGCCCGTGACCATCAGCTTCGCCAACCACACCAGCT 
                   
               
               
                 (AGS) 
                 GCAGATGCATGAGCAAGCTGGACGTGTACAGACAGGTGCAC 
                   
               
               
                   
                 AGCATCATCAGAAGA 
                   
               
               
                   
               
               
                 human VEGF- 
                 GCCCACTACAACACCGAGATCCTGAAGAGCATCGACAACGA 
                 40 
               
               
                 C mature 
                 GTGGAGAAAGACCCAGTGCATGCCCAGAGAGGTGGCCATCG 
                   
               
               
                 (dNdC) 
                 ACGTGGGCAAGGAGTTCGGCGTGGCCACCAACACCTTCTTCA 
                   
               
               
                 Cys137A1a 
                 AGCCCCCCTGCGTGAGCGTGTACAGATGCGGCGGCTGCTGCA 
                   
               
               
                 mutation 
                 ACAGCGAGGGCCTGCAGTGCATGAACACCAGCACCAGCTACC 
                   
               
               
                 codon 
                 TGAGCAAGACCCTGTTCGAGATCACCGTGCCCCTGAGCCAGG 
                   
               
               
                 optimized 2 
                 GCCCCAAGCCCGTGACCATCAGCTTCGCCAACCACACCAGCT 
                   
               
               
                 (AGS) 
                 GCAGATGCATGAGCAAGCTGGACGTGTACAGACAGGTGCAC 
                   
               
               
                   
                 AGCATCATCAGAAGA 
                   
               
               
                   
               
               
                 human VEGF- 
                 MHLLGFFSVACSLLAAALLPGPREAPAAAAAFESGLDLSDAEP 
                 41 
               
               
                 C full length 
                 DAGEATAYASKDLEEQLRSVSSVDELMTVLYPEYWKMYKCQLR 
                   
               
               
                 wt 
                 KGGWQHNREQANLNSRTEETIKFAAAHYNTEILKSIDNEWRKT 
                   
               
               
                   
                 QCMPREVCIDVGKEFGVATNTFFKPPCVSVYRCGGCCNSEGLQC 
                   
               
               
                   
                 MNTSTSYLSKTLFEITVPLSQGPKPVTISFANHTSCRCMSKLDVY 
                   
               
               
                   
                 RQVHSIIRRSLPATLPQCQAANKTCPTNYMWNNHICRCLAQEDF 
                   
               
               
                   
                 MFSSDAGDDSTDGFHDICGPNKELDEETCQCVCRAGLRPASCGP 
                   
               
               
                   
                 HKELDRNSCQCVCKNKLFPSQCGANREFDENTCQCVCKRTCPR 
                   
               
               
                   
                 NQPLNPGKCACECTESPQKCLLKGKKFHHQTCSCYRRPCTNRQ 
                   
               
               
                   
                 KACEPGFSYSEEVCRCVPSYWKRPQMS 
                   
               
               
                   
               
               
                 human VEGF- 
                 MHLLGFFSVACSLLAAALLPGPREAPAAAAAFESGLDLSDAEPD 
                 42 
               
               
                 C full length 
                 AGEATAYASKDLEEQLRSVSSVDELMTVLYPEYWKMYKCQLR 
                   
               
               
                 Cys156Ser 
                 KGGWQHNREQANLNSRTEETIKFAAAHYNTEILKSIDNEWRKT 
                   
               
               
                 mutation 
                 QCMPREVCIDVGKEFGVATNTFFKPPSVSVYRCGGCCNSEGLQC 
                   
               
               
                   
                 MNTSTSYLSKTLFEITVPLSQGPKPVTISFANHTSCRCMSKLDVY 
                   
               
               
                   
                 RQVHSIIRRSLPATLPQCQAANKTCPTNYMWNNHICRCLAQEDF 
                   
               
               
                   
                 MFSSDAGDDSTDGFHDICGPNKELDEETCQCVCRAGLRPASCGP 
                   
               
               
                   
                 HKELDRNSCQCVCKNKLFPSQCGANREFDENTCQCVCKRTCPR 
                   
               
               
                   
                 NQPLNPGKCACECTESPQKCLLKGKKFHHQTCSCYRRPCTNRQ 
                   
               
               
                   
                 KACEPGFSYSEEVCRCVPSYWKRPQMS 
                   
               
               
                   
               
               
                 human VEGF- 
                 MHLLGFFSVACSLLAAALLPGPREAPAAAAAFESGLDLSDAEPD 
                 43 
               
               
                 C full length 
                 AGEATAYASKDLEEQLRSVSSVDELMTVLYPEYWKMYKCQLR 
                   
               
               
                 Cys137Ala 
                 KGGWQHNREQANLNSRTEETIKFAAAHYNTEILKSIDNEWRKT 
                   
               
               
                 mutation 
                 QCMPREVAIDVGKEFGVATNTFFKPPCVSVYRCGGCCNSEGLQ 
                   
               
               
                   
                 CMNTSTSYLSKTLFEITVPLSQGPKPVTISFANHTSCRCMSKLDV 
                   
               
               
                   
                 YRQVHSIIRRSLPATLPQCQAANKTCPTNYMWNNHICRCLAQED 
                   
               
               
                   
                 FMFSSDAGDDSTDGFHDICGPNKELDEETCQCVCRAGLRPASCG 
                   
               
               
                   
                 PHKELDRNSCQCVCKNKLFPSQCGANREFDENTCQCVCKRTCP 
                   
               
               
                   
                 RNQPLNPGKCACECTESPQKCLLKGKKFHHQTCSCYRRPCTNR 
                   
               
               
                   
                 QKACEPGFSYSEEVCRCVPSYWKRPQMS 
                   
               
               
                   
               
               
                 human VEGF- 
                 AHYNTEILKSIDNEWRKTQCMPREVCIDVGKEFGVATNTFFKPP 
                 44 
               
               
                 C mature 
                 CVSVYRCGGCCNSEGLQCMNTSTSYLSKTLFEITVPLSQGPKPVT 
                   
               
               
                 (dNdC) wt 
                 ISFANHTSCRCMSKLDVYRQVHSIIRR 
                   
               
               
                   
               
               
                 human VEGF- 
                 AHYNTEILKSIDNEWRKTQCMPREVCIDVGKEFGVATNTFFKPP 
                 45 
               
               
                 C mature 
                 SVSVYRCGGCCNSEGLQCMNTSTSYLSKTLFEITVPLSQGPKPVT 
                   
               
               
                 (dNdC) 
                 ISFANHTSCRCMSKLDVYRQVHSIIRR 
                   
               
               
                 Cys156Ser 
                   
                   
               
               
                 mutation 
                   
                   
               
               
                   
               
               
                 human VEGF- 
                 AHYNTEILKSIDNEWRKTQCMPREVAIDVGKEFGVATNTFFKPP 
                 46 
               
               
                 C mature 
                 CVSVYRCGGCCNSEGLQCMNTSTSYLSKTLFEITVPLSQGPKPVT 
                   
               
               
                 (dNdC) 
                 ISFANHTSCRCMSKLDVYRQVHSIIRR 
                   
               
               
                 Cys137Ala 
                   
                   
               
               
                 mutation 
                   
                   
               
               
                   
               
               
                 5′-non-coding- 
                 CCGCGGTTAGAAAAAATACGGGTAGAACCGCCACC 
                 47 
               
               
                 region-for- 
                   
                   
               
               
                 NDV 
                   
                   
               
               
                   
               
               
                 5′-non-coding- 
                 GTCGACATTTTTAATTAAAATAGGGTGGGGAAGGTACCGCCA 
                 48 
               
               
                 region-for- 
                 CC 
                   
               
               
                 APMV4 
                   
                   
               
               
                   
               
               
                 Nucleotide 
                 cccgctccttccaccatgcacttgctgggcttctggtctctggcg 
                 49 
               
               
                 sequence for 
                 tgttccctgctcgccgctgcgctgctgccggggccccgcgacgcg 
                   
               
               
                 
                   Canis lupus 
                 
                 cccgccgccgccgccgccttcgaatcgggactcggcttctccgac 
                   
               
               
                 familiaris 
                 gcggagcccgacgcgggcgaggcccaggcgtatgcaggcaaagat 
                   
               
               
                 VEGF-C 
                 ttggaggaacagttgcgatcagcgtccagtgtagatgaactcatg 
                   
               
               
                 GenBank No. 
                 accgtactctacccagaatattggaaaatgtacaagtgtcagtta 
                   
               
               
                 XM_540047.6 
                 aggaaaggcggctggcagcgtaataaagaacagcccaacatcagt 
                   
               
               
                   
                 gcaagaacagaagagactataaaatttgctgcagcacattataat 
                   
               
               
                   
                 gcagagatcttgaaaagtattgataatgagtggagaaaaactcag 
                   
               
               
                   
                 tgcataccacgtgaggtgtgtatagatgtggggaaggagtttgga 
                   
               
               
                   
                 gcagcaacaaacaccttctttaaacctccatgtgtgtccgtctac 
                   
               
               
                   
                 agatgtggtggctgctgtaacagcgagggcctacagtgtatgaac 
                   
               
               
                   
                 accagcacaagccacctcagcaagacgttgtttgaaattacagtg 
                   
               
               
                   
                 cctctctctcaaggccccaaaccagtaacaatcagttttgccaat 
                   
               
               
                   
                 cacacttcctgccgatgcatgtctaaactggacgtttacagacaa 
                   
               
               
                   
                 gttcattccattattagacgttccctgccagcaacactaccacag 
                   
               
               
                   
                 tgccaagctgcaaacaagacttgccccacaaattacatctggaat 
                   
               
               
                   
                 aatcatctctgcagatgcctggctcagcaagattttatttttgcc 
                   
               
               
                   
                 tcaaattctggagatgactctacagatggattccatgacatctgt 
                   
               
               
                   
                 ggacctaacaaggagctagatgaagaaacgtgtcagtgtgtctgc 
                   
               
               
                   
                 agaggggggctccggccttccagctgtggaccccacaaggaacta 
                   
               
               
                   
                 gacagaaactcctgccagtgtgtctgtaaaaacaaactgttaccc 
                   
               
               
                   
                 aactcgtgtggggccaacagagaatttgatgaaaacacgtgccag 
                   
               
               
                   
                 tgcgtatgtaaaagaacctgcccaagaaatcaacccctaaaccct 
                   
               
               
                   
                 ggaaaatgtgcctgtgagtgtacagaaaattcacagaaatgcttc 
                   
               
               
                   
                 ttaaaaggaaagaaatttcaacatcaaacatgcagctgttacaga 
                   
               
               
                   
                 agaccgtgtacaaaccgactgaggcattgtgagcaaggacttata 
                   
               
               
                   
                 tttagtgaagaagtatgtcgctgtgtcccttcatactggaaaaga 
                   
               
               
                   
                 ccacagatgaactaagactgta 
                   
               
               
                   
                 ctgttttccagtttgccatttctttatcttggaaaaccgtgttgc 
                   
               
               
                   
                 cacattagaactatctgtgaacacagagaccttggtgggaccatg 
                   
               
               
                   
                 gagacagagacagaagtcagtgtttgctgacctgtgtggataact 
                   
               
               
                   
                 ttacagaaacggactggagctcatctgcaaaagacctcttttaat 
                   
               
               
                   
                 gactggtttttctgccaatgaccagacagctgaggtttttctctt 
                   
               
               
                   
                 gtgattaaaaaaaaaaaataatgactatataatttatttccacta 
                   
               
               
                   
                 aaaatattgtttctgcattcatgtttatagcaataacaattggta 
                   
               
               
                   
                 aagctcactgtgatcaatatttttatatcatgcaaaatatgttta 
                   
               
               
                   
                 aaataaaatgaaaattgtattataaa 
                   
               
               
                   
               
               
                 Nucleotide 
                 cccgctccttccaccatgcacttgctgggcttctggtctctggcg 
                 50 
               
               
                 sequence for 
                 tgttccctgctcgccgctgcgctgctgccggggccccgcgacgcg 
                   
               
               
                 
                   Canis lupus 
                 
                 cccgccgccgccgccgccttcgaatcgggactcggcttctccgac 
                   
               
               
                 dingo VEGF- 
                 gcggagcccgacgcgggcgaggcccaggcgtatgcaggcaaagat 
                   
               
               
                 C (GenBank 
                 ttggaggaacagttgcgatcagcgtccagtgtagatgaactcatg 
                   
               
               
                 Accession 
                 accgtactctacccagaatattggaaaatgtacaagtgtcagtta 
                   
               
               
                 NO. 
                 aggaaaggcggctggcagcgtaataaagaacagcccaacatcagt 
                   
               
               
                 XM_0254340 
                 gcaagaacagaagagactataaaatttgctgcagcacattataat 
                   
               
               
                 44) 
                 gcagagatcttgaaaagtattgataatgagtggagaaaaactcag 
                   
               
               
                   
                 tgcataccacgtgaggtgtgtatagatgtggggaaggagtttgga 
                   
               
               
                   
                 gcagcaacaaacaccttctttaaacctccatgtgtgtccgtctac 
                   
               
               
                   
                 agatgtggtggctgctgtaacagcgagggcctacagtgtatgaac 
                   
               
               
                   
                 accagcacaagccacctcagcaagacgttgtttgaaattacagtg 
                   
               
               
                   
                 cctctctctcaaggccccaaaccagtaacaatcagttttgccaat 
                   
               
               
                   
                 cacacttcctgccgatgcatgtctaaactggatgtttacagacaa 
                   
               
               
                   
                 gttcattccattattagacgttccctgccagcaacactaccacag 
                   
               
               
                   
                 tgccaagctgcaaacaagacttgccccacaaattacatctggaat 
                   
               
               
                   
                 aatcatctctgcagatgcctggctcagcaagattttatttttgcc 
                   
               
               
                   
                 tcaaattctggagatgactctacagatggattccatgacatctgt 
                   
               
               
                   
                 ggacctaacaaggagctagatgaagaaacgtgtcagtgtgtctgc 
                   
               
               
                   
                 agaggggggctccggccttccagctgtggaccccacaaggaacta 
                   
               
               
                   
                 gacagaaactcctgccagtgtgtctgtaaaaacaa 
                   
               
               
                   
                 actgttacccaactcgtgtggggccaacagagaatttgatgaaaa 
                   
               
               
                   
                 cacgtgccagtgcgtatgtaaaagaacctgcccaagaaatcaacc 
                   
               
               
                   
                 cctaaaccctggaaaatgtgcctgtgagtgtacagaaaattcaca 
                   
               
               
                   
                 gaaatgcttcttaaaaggaaagaaatttcaacatcaaacatgcag 
                   
               
               
                   
                 ctgttacagaagaccgtgtacaaaccgactgaggcattgtgagca 
                   
               
               
                   
                 aggacttatatttagtgaagaagtatgtcgctgtgtcccttcata 
                   
               
               
                   
                 ctggaaaagaccacagatgaactaagactgtactgttttccagtt 
                   
               
               
                   
                 tgccatttctttatcttggaaaaccgtgttgccacattagaacta 
                   
               
               
                   
                 tctgtgaacacagagaccttggtgggaccatggagacagagacag 
                   
               
               
                   
                 aagtcagtgtttgctgacctgtgtggataactttacagaaacgga 
                   
               
               
                   
                 ctggagctcatctgcaaaagacctcttttaatgactggtttttct 
                   
               
               
                   
                 gccaatgaccagacagctgaggtttttctcttgtgattaaaaaaa 
                   
               
               
                   
                 aaaaataatgactatataatttatttccactaaaaatattgtttc 
                   
               
               
                   
                 tgcattcatgtttatagcaataacaattggtaaagctcactgtga 
                   
               
               
                   
                 tcaatatttttatatcatgcaaaatatgtttaaaataaaatgaaa 
                   
               
               
                   
                 attgtattataaa 
                   
               
               
                   
               
               
                 
                   Canis Lupus 
                 
                 MHLLGFWSLACSLLAAALLPGPRDAPAAAAAFESGLGFSDAEP 
                 51 
               
               
                 Familiaris 
                 DAGEAQAYAGKDLEEQLRSASSVDELMTVLYPEYWKMYKCQL 
                   
               
               
                 VEGF-C 
                 RKGGWQRNKEQPNISARTEETIKFAAAHYNAEILKSIDNEWRKT 
                   
               
               
                 (GenBank 
                 QCIPREVCIDVGKEFGAATNTFFKPPCVSVYRCGGCCNSEGLQC 
                   
               
               
                 Accession No. 
                 MNTSTSHLSKTLFEITVPLSQGPKPVTISFANHTSCRCMSKLDVY 
                   
               
               
                 XP_540047.2) 
                 RQVHSIIRRSLPATLPQCQAANKTCPTNYIWNNHLCRCLAQQDFI 
                   
               
               
                   
                 FASNSGDDSTDGFHDICGPNKELDEETCQCVCRGGLRPSSCGPH 
                   
               
               
                   
                 KELDRNSCQCVCKNKLLPNSCGANREFDENTCQCVCKRTCPRN 
                   
               
               
                   
                 QPLNPGKCACECTENSQKCFLKGKKFQHQTCSCYRRPCTNRLR 
                   
               
               
                   
                 HCEQGLIFSEEVCRCVPSYWKRPQMN 
                   
               
               
                   
               
               
                 
                   Canis Lupus 
                 
                 MHLLGFWSLACSLLAAALLPGPRDAPAAAAAFESGLGFSDAEP 
                 52 
               
               
                 Dingo: 
                 DAGEAQAYAGKDLEEQLRSASSVDELMTVLYPEYWKMYKCQL 
                   
               
               
                 VEGF-C 
                 RKGGWQRNKEQPNISARTEETIKFAAAHYNAEILKSIDNEWRKT 
                   
               
               
                 (GenBank 
                 QCIPREVCIDVGKEFGAATNTFFKPPCVSVYRCGGCCNSEGLQC 
                   
               
               
                 Accession No. 
                 MNTSTSHLSKTLFEITVPLSQGPKPVTISFANHTSCRCMSKLDVY 
                   
               
               
                 XP 02528982 
                 RQVHSIIRRSLPATLPQCQAANKTCPTNYIWNNHLCRCLAQQDFI 
                   
               
               
                 9.1) 
                 FASNSGDDSTDGFHDICGPNKELDEETCQCVCRGGLRPSSCGPH 
                   
               
               
                   
                 KELDRNSCQCVCKNKLLPNSCGANREFDENTCQCVCKRTCPRN 
                   
               
               
                   
                 QPLNPGKCACECTENSQKCFLKGKKFQHQTCSCYRRPCTNRLR 
                   
               
               
                   
                 HCEQGLIFSEEVCRCVPSYWKRPQMN 
                   
               
               
                   
               
               
                 Human 
                 aagacacatg cttctgcaag cttccatgaa ggttgtgcaa aaaagtttca 
                 96 
               
               
                 vascular 
                 atccagagtt gggttccagc tttctgtagc tgtaagcatt ggtggccaca 
                   
               
               
                 endothelial 
                 ccacctcctt acaaagcaac tagaacctgc ggcatacatt ggagagattt 
                   
               
               
                 growth factor- 
                 ttttaatttt ctggacatga agtaaattta gagtgctttc taatttcagg 
                   
               
               
                 D (VEGF-D) 
                 tagaagacat gtccaccttc tgattatttt tggagaacat tttgattttt 
                   
               
               
                 GenBank No. 
                 ttcatctctc tctccccacc cctaagattg tgcaaaaaaa gcgtaccttg 
                   
               
               
                 NM_004469.5 
                 cctaattgaa ataatttcat tggattttga tcagaactga ttatttggtt 
                   
               
               
                 Uni-Prot. 
                 ttctgtgtga agttttgagg tttcaaactt tccttctgga gaatgccttt 
                   
               
               
                 043915 
                 tgaaacaatt ttctctagct gcctgatgtc aactgcttag taatcagtgg 
                   
               
               
                   
                 atattgaaat attcaaaatg tacagagagt gggtagtggt gaatgttttc 
                   
               
               
                   
                 atgatgttgt acgtccagct ggtgcagggc tccagtaatg aacatggacc 
                   
               
               
                   
                 agtgaagcga tcatctcagt ccacattgga acgatctgaa cagcagatca 
                   
               
               
                   
                 gggctgcttc tagtttggag gaactacttc gaattactca ctctgaggac 
                   
               
               
                   
                 tggaagctgt ggagatgcag gctgaggctc aaaagtttta ccagtatgga 
                   
               
               
                   
                 ctctcgctca gcatcccatc ggtccactag gtttgcggca actttctatg 
                   
               
               
                   
                 acattgaaac actaaaagtt atagatgaag aatggcaaag aactcagtgc 
                   
               
               
                   
                 agccctagag aaacgtgcgt ggaggtggcc agtgagctgg ggaagagtac 
                   
               
               
                   
                 caacacattc ttcaagcccc cttgtgtgaa cgtgttccga tgtggtggct 
                   
               
               
                   
                 gttgcaatga agagagcctt atctgtatga acaccagcac ctcgtacatt 
                   
               
               
                   
                 tccaaacagc tetttgagat atcagtgcct ttgacatcag tacctgaatt 
                   
               
               
                   
                 agtgcctgtt aaagttgcca atcatacagg ttgtaagtgc ttgccaacag 
                   
               
               
                   
                 ccccccgcca tccatactca attatcagaa gatccatcca gatccctgaa 
                   
               
               
                   
                 gaagatcgct gttcccattc caagaaactc tgtcctattg acatgctatg 
                   
               
               
                   
                 ggatagcaac aaatgtaaat gtgttttgca ggaggaaaat ccacttgctg 
                   
               
               
                   
                 gaacagaaga ccactctcat ctccaggaac cagctctctg tgggccacac 
                   
               
               
                   
                 atgatgtttg acgaagatcg ttgcgagtgt gtctgtaaaa caccatgtcc 
                   
               
               
                   
                 caaagatcta atccagcacc ccaaaaactg cagttgcttt gagtgcaaag 
                   
               
               
                   
                 aaagtctgga gacctgctgc cagaagcaca agctatttca cccagacacc 
                   
               
               
                   
                 tgcagctgtg aggacagatg cccctttcat accagaccat gtgcaagtgg 
                   
               
               
                   
                 caaaacagca tgtgcaaagc attgccgctt tccaaaggag aaaagggctg 
                   
               
               
                   
                 cccaggggcc ccacagccga aagaatcctt gattcagcgt tccaagttcc 
                   
               
               
                   
                 ccatccctgt catttttaac agcatgctgc tttgccaagt tgctgtcact 
                   
               
               
                   
                 gtttttttcc caggtgttaa aaaaaaaatc cattttacac agcaccacag 
                   
               
               
                   
                 tgaatccaga ccaaccttcc attcacacca gctaaggagt ccctggttca 
                   
               
               
                   
                 ttgatggatg tcttctagct gcagatgcct ctgcgcacca aggaatggag 
                   
               
               
                   
                 aggaggggac ccatgtaatc cttttgttta gttttgtttt tgttttttgg 
                   
               
               
                   
                 tgaatgagaa aggtgtgctg gtcatggaat ggcaggtgtc atatgactga 
                   
               
               
                   
                 ttactcagag cagatgagga aaactgtagt ctctgagtcc tttgctaatc 
                   
               
               
                   
                 gcaactcttg tgaattattc tgattctttt ttatgcagaa tttgattcgt 
                   
               
               
                   
                 atgatcagta ctgactttct gattactgtc cagcttatag tcttccagtt 
                   
               
               
                   
                 taatgaacta ccatctgatg tttcatattt aagtgtattt aaagaaaata 
                   
               
               
                   
                 aacaccatta ttcaagcca 
                   
               
               
                   
               
               
                 Canine 
                 ttttctgtgt gtccgtggca gtcgatgtgt gaacatctga ggtcccttcc 
                 97 
               
               
                 VEGF-D 
                 tgagcattgc gatttccatg caacattcat gcctgtgtgc tggggtttca 
                   
               
               
                 
                   Canis lupus 
                 
                 cgttacaggt tatctgcatt aaaataacag cagtcctgat ggtttgagtc 
                   
               
               
                 familiaris 
                 agttttcaaa actgccctgc tattggtagg gacgcgacag gattacagcc 
                   
               
               
                 GenBank No. 
                 aagacttccc tgcattttct gccaaagtct ctgtcagatt taagacacat 
                   
               
               
                 XM_548869.5 
                 gcttccgcaa ccttccatga gggttgtaaa aaaagtctga atccagaatt 
                   
               
               
                   
                 gggttccagc cttctgtggc tgcaaacatt ggtggccaca ccacctcctt 
                   
               
               
                   
                 acaaagcaac tagaacctgg ggcagagggt ggagagattt ttttttttaa 
                   
               
               
                   
                 tttgctggac atgaaatgaa tttagagtgc tttttcgtgt caagtggaag 
                   
               
               
                   
                 tcatgtccac ctcctgatta tttttggagc atgagtgcat ttaatttttt 
                   
               
               
                   
                 ttcatctctc tccccgcata agattgagca aaaacgttcc ttgactaatt 
                   
               
               
                   
                 gaagtcattt cattggattt tgatcacaac tgattatttg ggttttttcc 
                   
               
               
                   
                 atgtgaagtc ttggggtttc gaactttcct tctggagaat gccttttgaa 
                   
               
               
                   
                 acagttttct ctagctgcct gatgtcaact gcttggtaat cggtggacat 
                   
               
               
                   
                 taaaatactc aaaatgtaca gacagtgggc cgtggtgaat gttttcatga 
                   
               
               
                   
                 tgtcttatct acagttggtg cacagctcca gttatgagca tggaccagtg 
                   
               
               
                   
                 aagcgggcat ctcggtcaac gttagagcgg tctgaacagc agattagggc 
                   
               
               
                   
                 agcttctggt ttggaagaac tgctgcggat cacacacttc gaggactgga 
                   
               
               
                   
                 agctctggag atgccgactg aagctcaaaa gtttgaccag cacagactct 
                   
               
               
                   
                 cgctcagcat cccatcgggc caccaggttt gcggcaactt tctatgacat 
                   
               
               
                   
                 tgaaacccta aaagtcatag acgaggagtg gcagcggacg cagtgcagcc 
                   
               
               
                   
                 cccgggagac gtgcgtggag gtggccagcg agctggggag gagcaccgac 
                   
               
               
                   
                 acgttcttca agccgccctg cgtgaacgtg ttccgctgtg gcggctgctg 
                   
               
               
                   
                 caacgaggag agcctcgtct gtatgaacac gagcacctcc tacgtctcca 
                   
               
               
                   
                 aacagctctt tgagatatca gtgcctttga cttcagtacc tgaattagtg 
                   
               
               
                   
                 cctgttaagg tggccaacca tacaggttgt aagtgcctgc caacggctcc 
                   
               
               
                   
                 ccgccatcca tactccatta tcagaagatc catccagatc ccagaagaag 
                   
               
               
                   
                 atcactgttc ccattccaag caactctgtc ctgttgacat gctatgggat 
                   
               
               
                   
                 agcgacaaat gtaaatgtgt tttacaggag gagaatccac tcgttggaat 
                   
               
               
                   
                 ggaagaccac tctcacctcc aggaactggc tctctgcggg ccgcacatga 
                   
               
               
                   
                 agtttgacga cgatcgttgc gagtgtgtct gtaaaacacc gtgtcccaga 
                   
               
               
                   
                 gatctcatcc agcacccaga aaactgcagt tgcatggagt gcagagagag 
                   
               
               
                   
                 cctggagagc tgctgccaga agcacaagat atttcacgca gacacctgca 
                   
               
               
                   
                 gctgtgagga cagatgtccc tttcacacca gaacatgtgc gcatggaaga 
                   
               
               
                   
                 ccagcatgtg caaagcactg ccgctttccg aaggagaaaa gggctgccta 
                   
               
               
                   
                 tgggttccat ggtcaagaaa atccttgact caacttggtt cctgagttcc 
                   
               
               
                   
                 ccatccctaa cattttaaac agcatgctgc tttgccaagt tgctgtcact 
                   
               
               
                   
                 gattgttttt ttttccccac gtacaagaaa aaaaaatctg ttttacccag 
                   
               
               
                   
                 tcccacaatg aattcagacc acccttccat tacacaccag ctgaggcttc 
                   
               
               
                   
                 cctggttcac tgacagatga ctgccaactg aagatgcccc tgcacagcag 
                   
               
               
                   
                 gatggagagg agggaacctg tagcagcccc ctcccttttt tttttggtga 
                   
               
               
                   
                 atgttaaagg tctgatcatc ctagaatcac aggggccata aaattgatta 
                   
               
               
                   
                 ctcaaagcca acaaggcaat tttatagtct ccaagtcctt cgctaatgca 
                   
               
               
                   
                 gctgtcttgt gaattcttct gactctttat tatgcagatt ttgatttgta 
                   
               
               
                   
                 tgatcagcac tgattttctg attactgtcc agcttgtagt tttgagttta 
                   
               
               
                   
                 ctgaactact gtctgttgtt tcatatttaa gtgtatttaa agaaaataaa 
                   
               
               
                   
                 caccattatt caagccgtgg aa 
                   
               
               
                   
               
               
                 Canine 
                 ttttctgtgt gtccgtggca gtcgatgtgt gaacatctga ggtcccttcc 
                 98 
               
               
                 VEGF-D 
                 tgagcattgc gatttccatg caacattcat gcctgtgtgc tggggtttca 
                   
               
               
                 
                   Canis lupus 
                 
                 cgttacaggt tatctgcatt aaaataacag cagtcctgat ggtttgagtc 
                   
               
               
                 dingo 
                 agttttcaaa actgccctgc tattggtagg gacgcgacag gattacagcc 
                   
               
               
                 GenBank No. 
                 aagacttccc tgcattttct gccaaagtct ctgtcagatt taagacacat 
                   
               
               
                 XM_0254370 
                 gcttccgcaa ccttccatga gggttgtaaa aaaagtctga atccagaatt 
                   
               
               
                 83 
                 gggttccagc cttctgtggc tgcaaacatt ggtggccaca ccacctcctt 
                   
               
               
                   
                 acaaagcaac tagaacctgg ggcagagggt ggagagattt ttttttttaa 
                   
               
               
                   
                 tttgctggac atgaaatgaa tttagagtgc tttttcgtgt caagtggaag 
                   
               
               
                   
                 tcatgtccac ctcctgatta tttttggagc atgagtgcat ttaatttttt 
                   
               
               
                   
                 ttcatctctc tccccgcata agattgagca aaaacgttcc ttgactaatt 
                   
               
               
                   
                 gaagtcattt cattggattt tgatcacaac tgattatttg ggttttttcc 
                   
               
               
                   
                 atgtgaagtc ttggggtttc gaactttcct tctggagaat gccttttgaa 
                   
               
               
                   
                 acagttttct ctagctgcct gatgtcaact gcttggtaat cggtggacat 
                   
               
               
                   
                 taaaatactc aaaatgtaca gacagtgggc cgtggtgaat gttttcatga 
                   
               
               
                   
                 tgtcttatct acagttggtg cacagctcca gttatgagca tggaccagtg 
                   
               
               
                   
                 aagcgggcat ctcggtcaac gttagagcgg tctgaacagc agattagggc 
                   
               
               
                   
                 agcttctggt ttggaagaac tgctgcggat cacacacttc gaggactgga 
                   
               
               
                   
                 agctctggag atgccgactg aagctcaaaa gtttgaccag cacagactct 
                   
               
               
                   
                 cgctcagcat cccatcgggc caccaggttt gcggcaactt tctatgacat 
                   
               
               
                   
                 tgaaacccta aaagtcatag acgaggagtg gcagcggacg cagtgcagcc 
                   
               
               
                   
                 cccgggagac gtgcgtggag gtggccagcg agctggggag gagcaccgac 
                   
               
               
                   
                 acgttcttca agccgccctg cgtgaacgtg ttccgctgtg gcggctgctg 
                   
               
               
                   
                 caacgaggag agcctcgtct gtatgaacac gagcacctcc tacgtctcca 
                   
               
               
                   
                 aacagctctt tgagatatca gtgcctttga cttcagtacc tgaattagtg 
                   
               
               
                   
                 cctgttaagg tggccaacca tacaggttgt aagtgcctgc caacggctcc 
                   
               
               
                   
                 ccgccatcca tactccatta tcagaagatc catccagatc ccagaagaag 
                   
               
               
                   
                 atcactgttc ccattccaag caactctgtc ctgttgacat gctatgggat 
                   
               
               
                   
                 agcgacaaat gtaaatgtgt tttacaggag gagaatccac tcgttggaat 
                   
               
               
                   
                 ggaagaccac tctcacctcc aggaactggc tctctgcggg ccgcacatga 
                   
               
               
                   
                 agtttgacga cgatcgttgc gagtgtgtct gtaaaacacc gtgtcccaga 
                   
               
               
                   
                 gatctcatcc agcacccaga aaactgcagt tgcatggagt gcagagagag 
                   
               
               
                   
                 cctggagagc tgctgccaga agcacaagat atttcacgca gacacctgca 
                   
               
               
                   
                 gctgtgagga cagatgtccc tttcacacca gaacatgtgc gcatggaaga 
                   
               
               
                   
                 ccagcatgtg caaagcactg ccgctttccg aaggagaaaa gggctgccta 
                   
               
               
                   
                 tgggttccat ggtcaagaaa atccttgact caacttggtt cctgagttcc 
                   
               
               
                   
                 ccatccctaa cattttaaac agcatgctgc tttgccaagt tgctgtcact 
                   
               
               
                   
                 gattgttttt ttttccccac gtacaagaaa aaaaaatctg ttttacccag 
                   
               
               
                   
                 tcccacaatg aattcagacc acccttccat tacacaccag ctgaggcttc 
                   
               
               
                   
                 cctggttcac tgacagatga ctgccaactg aagatgcccc tgcacagcag 
                   
               
               
                   
                 gatggagagg agggaacctg tagcagcccc ctcccttttt ttttggtgaa 
                   
               
               
                   
                 tgttaaaggt ctgatcatcc tagaatcaca ggggccataa aattgattac 
                   
               
               
                   
                 tcaaagccaa caaggcaatt ttatagtctc caagtccttc gctaatgcag 
                   
               
               
                   
                 ctgtcttgtg aattcttctg actctttatt atgcagattt tgatttgtat 
                   
               
               
                   
                 gatcagcact gattttctga ttactgtcca gcttgtagtt ttgagtttac 
                   
               
               
                   
                 tgaactactg tctgttgttt catatttaag tgtatttaaa gaaaataaac 
                   
               
               
                   
                 accattattc aagccgtgga a 
                   
               
               
                   
               
               
                 
                   Canis Lupus 
                 
                 MYRQWAVVNVFMMSYLQLVHSSSYEHGPVKRASRSTLERSEQQIRAASGLEELLRITH 
                 99 
               
               
                 Dingo: 
                 FEDWKLWRCRLKLKSLTSTDSRSASHRATRFAATFYDIETLKVIDEEWQRTQCSPRETC 
                   
               
               
                 VEGF-D 
                 VEVASELGRSTDTFFKPPCVNVFRCGGCCNEESLVCMNTSTSYVSKQLFEISVPLTSVP 
                   
               
               
                 (GenBank 
                 ELVPVKVANHTGCKCLPTAPRHPYSIIRRSIQIPEEDHCSHSKQLCPVDMLWDSDKCKC 
                   
               
               
                 Accession No. 
                 VLQEENPLVGMEDHSHLQELALCGPHMKFDDDRCECVCKTPCPRDLIQHPENCSCMECR 
                   
               
               
                 XP 02529286 
                 ESLESCCQKHKIFHADTCSCEDRCPFHTRTCAHGRPACAKHCRFPKEKRAAYGFHGQEN 
                   
               
               
                 8.1) 
                 P 
                   
               
               
                   
               
               
                 
                   Canis Lupus 
                 
                 MYRQWAVVNVFMMSYLQLVHSSSYEHGPVKRASRSTLERSEQQIRAASGLEELLRITHF 
                 100 
               
               
                 
                   Familiaris 
                 
                 EDWKLWRCRLKLKSLTSTDSRSASHRATRFAATFYDIETLKVIDEEWQRTQCSPRETCV 
                   
               
               
                 VEGF-D 
                 EVASELGRSTDTFFKPPCVNVFRCGGCCNEESLVCMNTSTSYVSKQLFEISVPLTSVPE 
                   
               
               
                 (GenBank 
                 LVPVKVANHTGCKCLPTAPRHPYSIIRRSIQIPEEDHCSHSKQLCPVDMLWDSDKCKCV 
                   
               
               
                 Accession No. 
                 LQEENPLVGMEDHSHLQELALCGPHMKFDDDRCECVCKTPCPRDLIQHPENCSCMECRE 
                   
               
               
                 XP_548869.2) 
                 SLESCCQKHKIFHADTCSCEDRCPFHTRTCAHGRPACAKHCRFPKEKRAAYGFHGQEN 
                   
               
               
                   
                 P 
                   
               
               
                   
               
               
                   
               
               
                 Human ANAC 
                 FAATFYDIETLKVIDEEWQRTQCSPRETCVEVASELGKSTNTFFK 
                 101 
               
               
                 VEGF-D 
                 PPCVNVFRCGGCCNE 
                   
               
               
                 (mature, 
                 ESLICMNTSTSYISKQLFEISVPLTSVPELVPVKVANHTGCKCLPT 
                   
               
               
                 processed 
                 APRHPYSIIRR 
                   
               
               
                 VEGF-D) 
                   
                   
               
               
                   
               
               
                 Human 
                 SIQIPEEDRCSHSKKLCPIDMLWDSNKCKCVLQEENPLAGTEDHS 
                 102 
               
               
                 VEGF-D C- 
                 HLQEPALCGPHMMFD 
                   
               
               
                 terminal 
                 EDRCECVCKTPCPKDLIQHPKNCSCFECKESLETCCQKHKLFHP 
                   
               
               
                 propeptide 
                 DTCSCEDRCPFHTRPC 
                   
               
               
                   
                 ASGKTACAKHCRFPKEKRAAQGPHSRKNP 
                   
               
               
                   
               
               
                 Human 
                 SSNEHGPVKRSSQSTLERSEQQIRAASSLEELLRITHSEDWKLWR 
                 103 
               
               
                 VEGF-D N- 
                 CRLRLKSFTSMDSRS 
                   
               
               
                 terminal 
                 ASHRSTR 
                   
               
               
                 propeptide 
                   
                   
               
               
                   
               
               
                 Human 
                 MYREWVVVNV FMMLYVQLVQ GSSNEHGPVK RSSQSTLERS EQQIRAASSL 
                 104 
               
               
                 VEGF-D 
                 EELLRITHSE DWKLWRCRLR LKSFTSMDSR SASHRSTRFA ATFYDIETLK 
                   
               
               
                 (UniProt: 
                 VIDEEWQRTQ CSPRETCVEV ASELGKSTNT FFKPPCVNVF RCGGCCNEES 
                   
               
               
                 043915) 
                 LICMNTSTSY ISKQLFEISV PLTSVPELVP VKVANHTGCK CLPTAPRHPY 
                   
               
               
                   
                 SIIRRSIQIP EEDRCSHSKK LCPIDMLWDS NKCKCVLQEE NPLAGTEDHS 
                   
               
               
                   
                 HLQEPALCGP HMMFDEDRCE CVCKTPCPKD LIQHPKNCSC FECKESLETC 
                   
               
               
                   
                 CQKHKLFHPD TCSCEDRCPF HTRPCASGKT ACAKHCRFPK EKRAAQGPHS 
                   
               
               
                   
                 RKNP 
                   
               
               
                   
               
               
                 Human 
                 MYREWVVVNVFMMLYVQLVQG 
                 105 
               
               
                 VEGF-D 
                   
                   
               
               
                 signal peptide 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Other Sequences 
               
            
           
           
               
               
               
               
            
               
                   
                   
                   
                 SEQ 
               
               
                   
                   
                   
                 ID 
               
               
                   
                 Description 
                 Sequence 
                 NO: 
               
               
                   
                   
               
               
                   
                 Cleavage Site 
                 S116:  111 H-N-R-T-K-S/F 117   
                 91 
               
               
                   
                 Modification 
                   
                   
               
               
                   
                   
               
               
                   
                 Cleavage Site 
                 S116K:  111 H-N-K-T-K-S/F 117   
                 92 
               
               
                   
                 Modification 
                   
                   
               
               
                   
                   
               
               
                   
                 Cleavage Site 
                 S116M:  111 H-N-R-M-K-S/F 117   
                 93 
               
               
                   
                 Modification 
                   
                   
               
               
                   
                   
               
               
                   
                 Cleavage Site 
                 S116KM:  111 H-N-K-M-K-S/F-I 118   
                 94 
               
               
                   
                 Modification 
                   
                   
               
               
                   
                   
               
               
                   
                 Cleavage Site 
                 R116:  111 H-N-R-T-K-R/F-I 118   
                 95 
               
               
                   
                 Modification 
               
               
                   
                   
               
            
           
         
       
     
     6. EXAMPLES 
     6.1 Example 1: Construction of Recombinant Paramyxovirus-VEGF-C 
     Rescue of Recombinant Newcastle Disease Virus (rNDV). 
     The virus was rescued following a very well stablished protocol, already described (Ayllon J, Garcia-Sastre A, Martinez-Sobrido L. 2013, Rescue of recombinant Newcastle disease virus from cDNA. J Vis Exp. 2013 Oct. 11; (80). doi: 10.3791/50830), with a few modifications. A schematic of the protocol is shown in  FIG.  1   . Briefly, BSR-T7 cells in a 6 well plate were infected with a recombinant vaccinia virus that expresses the T7 RNA polymerase (MVA-T7) and transfected with plasmids pNDV-LaSota-L289A (SEQ ID NO: 85), pTM1.NP, pTM1.P and pTM1.L. The following day supernatant and cells were harvested from the plate and inoculated into 10 days-old embryonated chicken eggs to amplify the rescued virus. After 3 days of incubation, the allantoic fluid was harvested and analyzed by hemagglutination assay to detect the presence of rNDV. Hemagglutinin (HA) positive samples were further characterized to confirm the presence and expression of the inserted foreign genes. See Ayllon et al., Rescue of Recombinant Newcastle Disease Virus from cDNA. J. Vis. Exp. (80), e50830, doi:10.3791/50830 (2013) for a description of the methodology used to rescue recombinant NDV. 
     Construction of a Rescue Plasmid to Obtain a rNDV Expressing the Mouse Vascular Endothelial Growth Factor-C (mVEGF-C). 
     The Open Reading Frame of mouse VEGF-C was amplified from a synthetic cDNA corresponding to a codon optimized VEGF-C (SEQ ID NO: 7) by PCR using primers that incorporate the following sequences: Forward primer: Sac II restriction site+NDV regulatory sequences (gene end+intergene+gene start)+Kozac sequences for optimal translation. Reverse primer: additional nucleotides (rule of 6)+Sac II restriction site. See, e.g., Table 1 (SEQ ID NOS: 65 and 66) for primer sequences. 
     The size of the amplified insert was compliant with the rule of 6 to warrant efficient encapsidation of the genome by the viral nucleoprotein (NP). The PCR product was cloned into the unique Sac II site of the pNDV-LaSota-L289A plasmid (see, e.g., SEQ ID NO: 85). A schematic showing the construction of the rescue plasmid is shown in  FIG.  2   . After confirmation that the insert was present, the plasmid was used to rescue a rNDV expressing mVEGF-C as described above. Presence of the additional gene in the viral genome was confirmed by RT-PCR and expression of mVEGF-C was confirmed by immunological assays (ELISA and immunofluorescence) on infected Vero cells. 
     Cloning of a Full Length cDNA of the Genome of Avian Paramyxovirus 4 (APMV4). 
     Viral RNA was purified from a preparation of APMV4 (strain Duck/Hong Kong/D3/1975) amplified in embryonated eggs and concentrated by ultracentrifugation through a sucrose cushion. The genome sequence was confirmed by deep sequencing. Rapid Amplification of cDNA Ends (RACE) was used to confirm the sequence of the 5′ and 3′ ends. See SEQ ID NO: 86 for the full length genome of APMV4 from RNA sequencing. 
     The purified RNA was used as template in RT-PCR to amplify partial fragments corresponding to each viral gene. Primers were designed to introduce unique restriction sites at non-conserved parts of the intergenic regions. See Table 1 and SEQ ID NOS: 53-56 and 67-76 for primer sequences. Next, the amplified RT-PCR fragments were cloned in the multicloning site of plasmid pUC-18 to generate intermediate plasmids pUC-APMV4-1 (with genes NP, P and M), pUC-APMV4-2 (with genes F and HN) and pUC-APMV4-3 (with gene L). The inserts of plasmids 1 and 2 were ligated to generate plasmid pUC-APMV4-1+2 and finally the complete genome was assembled in plasmid pUC-APMV4-1+2+3. 
     Next, the full length cDNA of the APMV4 viral genome was subcloned into the final rescue plasmid pRz-APMV4, under the control of the T7 RNA polymerase promoter and terminator sequences and flanked by ribozymes to generate the correct 5′ and 3′ ends. In this plasmid the Sal I site engineered between the viral genes P and M is not unique. A schematic showing the cloning of a full-length cDNA of the APMV4 genome is shown in  FIG.  3   . 
     Cloning of Helper Plasmids Expressing the APMV4 Proteins NP, P and L Under the Control of the T7 RNA Polymerase. 
     To generate the APMV4 helper plasmids, the open reading frames of viral genes NP, P and L were amplified using as templates plasmids pUC-APMV4-1 (for genes NP and P) and pUC-APMV4-3 (for gene L). See, e.g., Table 1 and SEQ ID NOS: 57-62 for primer sequences. The PCR amplified products were cloned into the expression plasmid pTM1 using the restriction sites Nco I and Pst I. A schematic showing the protocol for the cloning of the helper plasmids is shown in  FIG.  4   . 
     Rescue of Recombinant APMV4. 
     The virus is rescued following the same protocol described above for rNDV (schematic of the protocol shown in  FIG.  5   ). Briefly, BSR-T7 cells in a 6 well plate are infected with a recombinant vaccinia virus that expresses the T7 RNA polymerase (MVA-T7) and transfected with plasmids pRz-APMV4, pTM1-APMV4.NP, pTM1-APMV4.P and pTM1-APMV4.L. The following day supernatant and cells are harvested from the plate and inoculated into 10 days-old embryonated chicken eggs to amplify the rescued virus. After a three-day incubation, the allantoic fluid is harvested and analyzed by hemagglutination assay to detect the presence of rAPMV4. HA positive samples are further characterized to confirm the presence and expression of the inserted foreign genes. 
     Construction of a Rescue Plasmid to Obtain a rAPMV4 Expressing the Mouse Vascular Endothelial Growth Factor-C (mVEGF-C). 
     The rescue plasmid to obtain a rAPMV4-mVEGF-C was prepared as described for the rNDV above, but using as template a synthetic sequence with a codon-optimized mVEGF-C gene. The codon-optimized sequence was designed using the web based tool at www.encorbio.com/protocols/Codon.htm. 
     Next, the optimized Open Reading Frame of mVEGF-C was amplified by PCR using primers that incorporate the following sequences: Forward primer: Sal I restriction site+APMV regulatory sequences (gene end+intergene+gene start)+Kozac sequences for optimal translation. Reverse primer: additional nucleotides (rule of 6)+Sal I restriction site. See, e.g., Table 1 and SEQ ID Nos: 63 and 64 for primer sequences, SEQ ID NO: 13 for codon optimized mVEGF-C sequence, and SEQ ID NO: 89 for codon optimized mouse VEGF-C sequence plus regulatory sequences. 
     The size of the amplified insert was compliant with the rule of 6 to warrant efficient encapsidation of the genome by the viral NP. The PCR product was cloned into the Sal I site of the pRz-APMV4 plasmid. Because the Sal I site is not unique, the cloning was done in 2 steps: 1) the PCR product was cloned in the unique Sal I site of plasmid pUC-APMV4-1; and 2) A Nhe I-Sbf I restriction fragment (containing the mVEGF-C gene) was subcloned into plasmid pRz-APMV4. See, e.g., SEQ ID NO: 90 for plasmid pRz-APMV4 sequence. After confirmation of the presence of mVEGF-C, the plasmid is used to rescue a rAPMV4 expressing mVEGF-C as described above. Presence of the additional gene in the viral genome is confirmed by RT-PCR and expression of mVEGF-C is confirmed by immunological assays (ELISA and immune-fluorescence) on infected Vero cells. A schematic showing the protocol for the construction of the rescue plasmid pRz-APMV4-mVEGF-C is shown in  FIG.  6   . 
     6.2 Example 2: Oncolytic Activity of APMVs in B16-F10 and B16-VEGF-C+ Syngeneic Murine Melanoma Tumor Models 
     Tumor Growth Curves and Long-Term Survival 
     B16-F10 or B16-VEGF-C+ cells were implanted in the flank of the right posterior leg of C57BL/6 mice. Starting once the primary tumor reached a volume of 50 mm 3  (about day 12 post-implantation of B16-F10 or B16-VEGF-C+ cells), the animals were intratumorally treated every other day (days 12, 14, 16, and 18) with a total of four doses of 10 7  PFU of LS-L289A, 10 7  PFU of APMV-4, or 50 μl of PBS for control mice. Tumor volume was monitored every 48 hours or every 24 hours when approaching the experimental end point of a diameter of 1 cm (≥500 mm 3 ), after which mice were euthanized. Body weight was monitored every 48 hours. 
       FIG.  7 A  shows a schematic of the experimental set up for Study 1. An analysis of tumor growth rate is shown in  FIG.  7 B  (points represent average of tumor volume per experimental group at the indicated time point; error bars correspond to standard deviation of each group) and  FIG.  7 C  (individual tumor growth curves; each point represents tumor volume per mice at the indicated time point). Data showing overall survival and a, comparative analysis between experimental groups of treated B16-F10 or B16-VEGF-C+ tumor-bearing mice are shown in  FIGS.  7 D  an  7 E, respectively. 
       FIG.  9 A  shows a schematic of the experimental set up for Study 2. An analysis of tumor growth rate is shown in  FIG.  9 B  (points represent average of tumor volume per experimental group at the indicated time point, error bars correspond to SD of each group) and  FIG.  9 C  (individual tumor growth curves, each point represents tumor volume per mice at the indicated time point).  FIG.  8 D  shows an overall survival analysis pre-re-challenge. 
     Re-Challenge 
     Long term survivors displaying complete remission (CR) of the primary tumor (day 94) were intradermally implanted with 3×10 5  B16-F10 in the flank of the contralateral leg. As for the primary lesion, tumor volume and body weight loss were monitored every 48 hours or every 24 hours when the last volume estimation was approaching the experimental endpoint of a diameter of 1 cm (≥500 mm 3 ). 
       FIG.  8 A  shows a schematic of the re-challenge experimental set up for the Study 1 (right panel) and an analysis of tumor growth rate (left panel). Points represent average of tumor volume per experimental group at the indicated time point. Error bars correspond to standard deviation of each group.  FIG.  8 B  shows individual tumor growth curves. Each point represents tumor volume per mice at the indicated time point.  FIG.  8 C  shows a post-re-challenge overall survival analysis of Study 1. 
       FIG.  10 A  shows a schematic of the re-challenge experimental set up for Study 2. An analysis of tumor growth rate is shown in  FIG.  10 B . Points represent average of tumor volume per experimental group at the indicated time point. Error bars correspond to standard deviation of each group.  FIG.  10 C  shows survival post-re-challenge.  FIG.  10 D  shows a survival analysis summary for Study 2. 
     The data demonstrates that the administration of NDV or APMV-4 to VEGF-C positive tumors increases the survival of animals and decreases the size of the tumors. In addition, the data demonstrates that re-challenge of animals that were administered NDV or APMV-4 and display complete remission of the primary tumors post-administration have reduced tumor volume and increased survival. 
     6.3 Example 3: VEGF-C Potentiates Anti-Tumor Immune Response Stimulated by the Viral dsRNA Mimic Poly(I:C) 
     Experimental Design 
     B16F10 or B16F10/VEGF-C+ cells (5×10 5 ) were injected intradermally into C57BL6/J mice. Each mouse received two injections into the skin on lower back, left and right. On Day 7 (tumor volume 50 mm 3 ) and 10 post tumor injection, 50 μg of Poly(I:C) or PBS control was injected intratumorally. Tumor volume was monitored by caliper and mice were euthanized when tumor diameter reached 10 mm on any axis.  FIG.  11 A  shows a schematic of the study design. 
     Results 
     Data shown in  FIGS.  11 B and  11 C  shows tumor growth upon stimulation in B16F10 with Poly(I:C) with or without VEGF-C, or with a combination of both VEGFC and Poly(I:C), as indicated.  FIG.  11 B  shows average tumor volume per experimental group+/−standard deviation, individual tumor growth curves are shown in  FIG.  11 C . 
     6.4 Example 4: NDV-VEGF-C Constructs 
     This example demonstrates that recombinant NDV-VEGF-C constructs expressing the full length VEGF-C are able to reduce tumor growth and extend survival of mice implanted with B16F10 tumors. 
     6.4.1 Methods 
     6.4.1.1 Recombinant NDV-VEGF-C 
     6 recombinant NDV-VEGF-C viral constructs were produced as described in Example 1, supra. Nucleotide sequences encoding the 6 VEGF-C constructs are disclosed in Table 5. As shown in  FIG.  12   , to generate each of the 6 recombinant NDV-VEGF-C viral constructs, the nucleotide sequence of VEGF-C construct was inserted between P and M transcription units of the cDNA sequence of the NDV LaSota strain genome. 
     6.4.1.2 Immunofluorescent Staining of Cells In Vitro. 
     Wells of glass slides were seeded with 5×10 4  Vero cells and Vero cells were infected with different dilutions of the NDV viral constructs (“NDV-VEGF-C”). After 12 hr, cells were washed with PBS and fixed in 10% formalin for 10 minutes at room temperature (RT). Cells were rinsed with PBS at RT for 5 min. Fixed cells were blocked with 1% goat serum in PBS-Tween 20 (0.5%) for 1 h at RT. Cells were then incubated with anti-VEGFC primary antibody (R&amp;D, AF752,) diluted 1:100 in 1% goat serum-PBS-Tween 20 0.5% at RT for 1 hr. Secondary anti-goat Alexa-594 antibody (Jackson Immunoresearch, 705-586-147) was diluted 1:500 in 1% goat serum PBS-Tween 20 0.5% and the cells were incubated with secondary antibody at RT for 1 h. 
     6.4.1.3 ELISA 
     293T cells were transfected with the different constructs and incubated with serum-free cell culture media for 24 hours. After 24 h, the media was collected, centrifuged and filtered. 50 μl of the conditioned media were analyzed by ELISA following the manufacturer instructions (R&amp;D, cat. DVE00). 
     6.4.1.4 Western Blot Analysis. 
     293T cells were transfected with the different viral constructs and supernatants were collected after 24 hr. 8 ml of each sample was loaded on an Amicon Ultra 15 3k filter (Cat 900324). Samples were centrifuged at 4000 g for 1 h at 4° C. and the volume of all samples was adjusted to 310 μl. 20 μl of each concentrated sample were mixed with 10 μl of 6× Laemmli buffer, heated at 96° C. for 5 minutes, and loaded onto 15% agarose gel. Western blotting was performed using chemiluminescence. 
     6.4.1.5 Mouse Tumor Studies. 
     C57BL mice were injected with 5×10 5  B16F10 cells, 8-10 mice per group. Tumors were allowed to grow and virus treatment was started when tumors reached 5 mm. PBS (control group) or 1×10 7  viral PFU of NDV or NDV/VEGF-C were administered to the mice intratumorally in 100 μl of PBS every 2 days. A total of 4 injections were administered to each mouse. Tumor volume was measured every two days. 
     6.4.1.6 Immunohistochemistry. 
     Immunohistochemistry was performed on paraffin-embedded tissue sections using the Leica Bond RX automated immunostainer (Leica Biosystems), according to the Leica staining protocol. Briefly, all slides were deparaffinized using a heated Bond™ Dewax Solution (Leica cat. no. AR9222) and washed with 1× Bond™ Wash Solution (Leica cat. no. AR9590). Epitope retrievals were carried out for 20 minutes using the citrate-based Bond™ Epitope Retrieval 1 solution (Leica cat. no. AR9961). Slides were then blocked with a 3-4% v/v hydrogen peroxide block for five minutes that is included in the Bond™ Polymer Refine Detection kit (Leica cat. no. DS9800) and used for DAB staining. All antibodies were diluted using Bond™ Primary Antibody Diluent (Leica Biosystems AR9352). The following antibodies and dilutions were used: VEGF-C (R&amp;D, cat. number: AR752), LYVE-1 (Angiobio, Cat. number: 11-033) 1:100, CD8 (Biolegend, Cat. number: 100701), 1:300, goat anti-rat HRP (ThermoScientific, cat. number 31470) 1:1000, donkey anti-goat HRP (Jackson Immunoresearch, cat. number 705036147). 
     6.4.2 Results 
     6.4.2.1 NDV/VEGF-C Engineered Constructs with Six VEGF-C Variants 
     We generated six different NDV constructs by inserting VEGF-C between P (phosphoprotein) and M (matrix protein) regions of NDV ( FIG.  12   ). The resulting NDV/VEGF-C constructs comprised one of three full length VEGF-C variants one of three mature VEGF-C variants (fully proteolytically processed forms) with mutations generated to improve binding affinity to its receptor and/or stability (Joukov, 1997, “Proteolytic processing regulates receptor specificity and activity of VEGF-C.” EMBO J. 116(13):3898-911; Anisimov, 2009, “Activated forms of VEGF-C and VEGF-D provide improved vascular function in skeletal muscle.” Circ Res. 104(11):1302-12; Jeltsch, 2014, “CCBE1 enhances lymphangiogenesis via A disintegrin and metalloprotease with thrombospondin motifs-3-mediated vascular endothelial growth factor-C activation.” Circulation. 129(19):1962-71). Details regarding the VEGF-C variants are provided in Table 5. 
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 VEGF-C Construct 
               
            
           
           
               
               
               
               
            
               
                   
                 Sequence 
                   
                 Short 
               
               
                 Construct full name 
                 number 
                 Full designation 
                 designation 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 mouse VEGF- C full length wt 
                 7 
                 SN1 VEGF-C FL 
                 FL - WT 
               
               
                 codon optimized 
                   
                 WT 
               
               
                 mouse VEGF- C full length 
                 9 
                 SN2 VEGF-C FL 
                 FL - 133A 
               
               
                 Cys133Ala mutation codon 
                   
                 133A 
               
               
                 optimized 
               
               
                 mouse VEGF- C full length 
                 8 
                 SN3 VEGF-C FL 
                 FL - 152S 
               
               
                 Cys152Ser mutation codon 
                   
                 152S 
               
               
                 optimized 
               
               
                 mouse VEGF- C mature 
                 10 
                 SN4 VEGF-C 
                 dNdC - WT 
               
               
                 (dNdC) wt codon optimized 
                   
                 DNDC WT 
               
               
                 mouse VEGF- C mature 
                 12 
                 SN5 VEGF-C 
                 dNdC - 133A 
               
               
                 (dNdC) Cys133Ala mutation 
                   
                 DNDC 133A 
               
               
                 codon optimized 
               
               
                 mouse VEGF- C mature 
                 11 
                 SN6 VEGF-C 
                 dNdC - 152S 
               
               
                 (dNdC) Cys152Ser mutation 
                   
                 DNDC 152S 
               
               
                 codon optimized 
               
               
                   
               
            
           
         
       
     
     Transduction of Vero cells with NDV-VEGF-C FL-WT resulted in high expression levels of VEGF-C by these cells in vitro ( FIG.  13 A ). High levels of VEGF-C protein (˜7-9 ng/ml) were detected by ELISA in supernatants of 293T cells transfected with each of the six different VEGF-C variants ( FIG.  13 B ). Furthermore, Western Blot analysis showed the expected pattern of proteolytically processed forms of VEGF-C for each construct ( FIG.  13 C ). VEGF-C is synthesized as a precursor in which the central VEGF homology domain (VHD) is flanked by N- and C-terminal pro-peptides. Proteolytic removal of the pro-peptides increases VEGF-C affinity for VEGFR-3, and the resulting mature protein can also activate the major angiogenic receptor VEGFR-2 (Joukov et al., 1997 EMBO J. 116(13):3898-911; Jeltsch et al., Circulation. 2014 May 13; 129(19):1962-71)). Western blot analysis demonstrated that each of the three constructs comprising a full length form of VEGF-C produced mainly intermediately processed form of VEGF-C (˜33 kDa) ( FIG.  13 C ) which is believed to have high affinity for VEGFR-3. In contrast, each of the three constructs comprising a mature form of VEGF-C (ΔNΔC) produced mainly 21 kDa protein ( FIG.  13 C ) which binds VEGFR-2 in addition to VEGFR-3. Together, these data demonstrate that different VEGF-C variants engineered into NDV are expressed correctly and at high levels by cells transduced with the NDV containing the VEGF-C construct in vitro. 
     6.4.3 Effects of Treatments with NDV/VEGF-C on Tumor Growth and Survival 
     The efficacy of engineered NDV-VEGF-C wild-type (“wt”) constructs on inhibition of tumor growth was evaluated in mice. B16F10 tumors were treated by four intra-tumoral injections of NDV-VEGF-C and monitored for tumor growth and survival ( FIG.  14 A ). Treatment with NDV-VEGF-C construct expressing full length, wild-type (wt) VEGF-C significantly extended survival of treated mice ( FIG.  14 B ). Monitoring of tumor growth showed delayed tumor growth in mice treated with NDV-VEGF-C FL-WT, but not with NDV-VEGF-C dNdC-WT ( FIGS.  14 C and  14 D ). In accordance with these data, treatment with NDV-VEGF-C FL-WT extended life-span of animals, whereas treatment with NDV-VEGF-C dNdC-WT did not ( FIG.  14 E ). Immunostaining of tumors with an anti-VEGF-C antibody resulted in a strong signal, indicating that high levels of VEGF-C protein are produced in tumors upon administration of NDV-VEGF-C FL-WT ( FIG.  14 F ). Furthermore, immunostaining for lymphatic vessels using an anti-LYVE-1 antibody showed enlarged lymphatics and increased densities of lymphatics in NDV/VEGF-C treated tumors, indicating that functional VEGF-C has been produced ( FIG.  14 F ). Finally, NDV-VEGF-C treatment lead to a striking increase of CD8+ T-cell densities in tumors, that were uniformly distributed throughout ( FIG.  14 F ). Taken together, these data demonstrate that the NDV-VEGF-C wild type full length construct (WT-FL) effectively reduces tumor growth and extends survival, whereas NDV-VEGF-C dNdC-WT variant does not. These data further indicate that the anti-tumor effects of VEGF-C are likely mediated through VEGFR-3 and not through VEGFR-2. 
     6.5 Example 5: In Vivo Effects of NDV/VEGF-C 
     6.5.1 methods 
     6.5.1.1 Mouse Experiments. 
     B16F10 or B16F10-VEGF-C tumor cells (5×10 5  cells in 100 μl serum-free media) were injected intradermally into the right flank of six to eight-week-old mice (Jackson, C57B1/6J, cat. 000664). Mouse weights and tumor sizes were measured every two days. Treatment was started when tumors reached 5 mm in size. 50 μL of a solution containing PBS or NDV (10 7 PFUs/dose) were administered to the mice intratumorally every two days for a total of 4 treatments. Mice were monitored until humane endpoint. Mouse experiments were performed in accordance with protocols approved by the Institutional Animal Care and Use Committee (IACUC). 
     6.5.1.2 Flow Cytometry. 
     Flow cytometry was done using Aurora Spectral Cytometer (Cytek Biosciences) or LSR Fortessa X-20 (BD Biosciences). In brief, tissues were dissected and minced in a sterile petri dish in ice cold PBS (Invitrogen). Tumor tissues were dissociated with Mouse Tumor Dissociation Kit (Miltenyi) enzymes in Octomacs Dissociator with Heaters (Miltenyi). Lymph nodes were dissociated with Collagenase D enzyme (1 mg/ml, Roche) in a 37° C. water bath for 1 hour. Dissociation reactions were stopped with the addition of ice-cold FACS buffer (1% FBS, 0.09% NaN3 in PBS). Erythrocytes were lysed using RBC lysis (eBioscience) for 1 minute on ice. Lysis was stopped by the addition of ice-cold FACS buffer. Dissociated tissues were pressed through a 70 μM nylon filter to create a single cell suspension. Cell yield and viability were determined using Countess II Automated Cell Counter (ThermoFisher). Samples were stained with primary antibodies (see Table 6 below) targeting cell surface markers for 30 minutes on ice (1.0×10 6  cells/100 μL). Cells were then fixed and permeabilized with FOXP3 Transcription Factor Staining Buffer Set (eBioscience). Samples were then stained with primary antibodies targeting intracellular markers. Compensation and reference groups were calculated using UltraComp beads (eBioscience). Dead cells were excluded using LIVE/DEAD Fixable Yellow Dead Cell Stain Kit (Molecular Probes). 2.0×10 4 -1.0×10 5  viable CD45+ cells were acquired/sample. Flow Cytometry Data Analysis was done in FCS Express Version 7.0 and Cytobank. tSNE analysis was done in FCS Express with 500 iterations, Barnes-Hut Approximation of 0.5, and perplexity of 0.3. SPADE analysis was done in Cytobank 
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 Antibodies used for Spectral and Flow Cytometry 
               
            
           
           
               
               
               
               
            
               
                   
                   
                   
                 Concentration (μg 
               
               
                 Antibody 
                 Fluorochrome 
                 Clone 
                 antibody/1.0 × 10 6  cells) 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 F4/80 
                 BV-421 
                 Biolegend (BM8) 
                 0.1 
               
               
                 CD80 
                 V450 
                 BD Biosciences (16- 
                 0.1 
               
               
                   
                   
                 10A1) 
               
               
                 CD45 
                 BV480 
                 Biolegend (30-F11) 
                 0.08 
               
               
                 CD83 
                 BV650 
                 Biolegend (Michel-19) 
                 0.1 
               
               
                 PD-L1 
                 BV711 
                 BD Biosciences 
                 0.1 
               
               
                   
                   
                 (M1H5) 
               
               
                 MHCII 
                 BV785 
                 Biolegend 
                 0.08 
               
               
                   
                   
                 (M5/114.15.2) 
               
               
                 CD86 
                 FITC 
                 Biolegend (GL-1) 
                 0.1 
               
               
                 CD11C 
                 PerCP 
                 Biolegend (N418) 
                 0.2 
               
               
                 CD64 
                 PerCPCy5.5 
                 Biolegend (X54-5/7.1) 
                 0.2 
               
               
                 CD103 
                 PE 
                 Biolegend (2E7) 
                 0.1 
               
               
                 B220 
                 PECF594 
                 BD Biosciences (RA3- 
                 0.07 
               
               
                   
                   
                 6B2) 
               
               
                 Ly6G 
                 Pe-Cy7 
                 Biolegend (1A8) 
                 0.08 
               
               
                 CD11B 
                 APC 
                 Biolegend (M1/70) 
                 0.08 
               
               
                 CD49B 
                 AF647 
                 Biolegend (HMα2) 
                 0.1 
               
               
                 Ly6C 
                 AF700 
                 Biolegend (HK1.1) 
                 0.07 
               
               
                 CCR2 
                 APCFire750 
                 Biolegend 
                 0.1 
               
               
                   
                   
                 (SA203G11) 
               
               
                 CD62L 
                 BV421 
                 Biolegend (MEL-14) 
                 0.1 
               
               
                 KLRG1 
                 V450 
                 BD Biosciences (2F1) 
                 0.1 
               
               
                 CD8 
                 BV510 
                 Biolegend (53-6.7) 
                 0.1 
               
               
                 CD4 
                 PerCPEF710 
                 ThermoFisher (GK1.5) 
                 0.08 
               
               
                 CD3 
                 BV750 
                 BD Biosciences (SK7) 
                 0.1 
               
               
                 CXCR3 
                 BV650 
                 BD Biosciences 
                 0.1 
               
               
                   
                   
                 (CXCR3-173) 
               
               
                 CD28 
                 AF488 
                 Biolegend (E18) 
                 0.1 
               
               
                 CD25 
                 APC 
                 Biolegend (PC61) 
                 0.2 
               
               
                 CTLA4 
                 APCR700 
                 BD Biosciences 
                 0.1 
               
               
                   
                   
                 (UC10-4F10-11) 
               
               
                 CD44 
                 APCFire750 
                 Biolegend (IM7) 
                 0.1 
               
               
                 FOXP3 
                 V450 
                 BD Biosciences 
                 0.2 
               
               
                   
                   
                 (MF23) 
               
               
                 NK1.1 
                 BV650 
                 Biolegend (PK136) 
                 0.1 
               
               
                 IFNg 
                 BV711 
                 Biolegend (XMG1.2) 
                 0.1 
               
               
                 TNFα 
                 BB700 
                 BD Biosciences (MP6- 
                 0.1 
               
               
                   
                   
                 XT22) 
               
               
                 GrB 
                 FITC 
                 Biolegend (GB11) 
                 0.1 
               
               
                 PD1 
                 BV605 
                 Biolegend (29F.1A12) 
                 0.1 
               
               
                   
               
            
           
         
       
     
     6.5.1.3 Immunofluorescent Staining 
     Immunofluorescent staining was performed on fresh-frozen acetone/methanol fixed tissue sections. Briefly, all slides were fixed in cold acetone for 5 minutes followed by 2 minutes in cold 80% methanol. All primary antibodies were diluted in PBS-BSA 3% and incubated for 2 hours at room temperature. Secondary antibodies were incubated for 1 hour at room temperature. The following antibodies and dilutions were used: CD8 (Biolegend, cat. number: 100701) 1:300, CD4 (Biolegend, cat. number 100505) 1:300, CD11c (Biolegend, cat. number: 117301) 1:300, goat anti-rat AlexaFluor594 (Molecular Probes, cat. number: A11007), goat anti-armenian hamster FITC (Jackson Immunoresearch, cat. number: 127-095-160). For quantification of immunostaining images were acquired and quantified using NIS image software (Nikon). 
     6.5.2 Results: 
     6.5.2.1 NDV Treatment Leads to Complete Tumor Regression and Long-Term Survival of Mice with VEGF-C Expressing Melanomas 
     To examine the effects of NDV oncolytic viral therapy on tumors expressing VEGF-C, B16F10 or B16F10/VEGF-C mouse melanomas were treated with intra-tumoral injections of NDV every two days, for total of four treatments ( FIG.  15 A ). NDV treatment of B16F10 tumors led to significant tumor growth reduction and extended life of mice, but eventually all mice developed large tumors and had to be sacrificed. In contrast, NDV treatment of B16F10 tumors expressing VEGF-C led to complete inhibition of tumor growth and eradication of tumors in 70% of the animals (Complete response—CR: B16F10-NDV, 0/10; B16F10/VEGF-C-NDV, 7/10) ( FIGS.  15 B and  15 C ). Mice whose tumors were eliminated showed vitiligo at the tumor site shortly after tumor rejection, and were recognizable as survivors based on the white patches of hair ( FIG.  15 D ). Longitudinal analysis of animals in different treatment groups showed long-term survival only in mice that had VEGF-C expressing tumors treated with NDV ( FIG.  15 E ). Survivor mice have remained healthy for over a year at this point (data not shown). Upon re-challenge with B16F10 tumor cells, 33% of mice were protected from developing tumors in NDV/VEGF-C group only ( FIG.  15 F ). These data demonstrate that combination of NDV and VEGF-C in tumors has potent anti-tumor effect, leading to long-term survival after tumor eradication in majority of the animals. 
     6.5.2.2 Immunophenotyping Reveals Unique Immune Cell Subtypes in Tumors Expressing VEGF-C and Treated with NDV 
     The underlying immunological basis of tumor rejection driven by NDV and VEGF-C was investigated by performing immunophenotyping of tumor immune cells using Aurora spectral flow cytometry. Analysis of immune cell subtypes in different treatment groups clearly revealed enriched and unique immune cell populations in NDV/VEGF-C tumors. An intracellular flow cytometry panel revealed multiple subsets of CD8+, T-cells, CD4+ T-cells and NK cells uniquely activated in NDV/VEGF-C tumors compared to control, PBS-treated B16F10 ( FIG.  16 A ). NDV-treated B16F10/VEGF-C tumors were particularly enriched in activated CD8+ T-cells compared to NDV-treated tumors not expressing VEGF-C ( FIG.  16 B ). Comparison of all four treatment groups clearly showed that several CD8+ T-cell subsets were predominantly seen in NDV/VEGF-C tumors ( FIG.  16 C ). Among these, prominent subtypes included CD4-CD8− T-cells that expressed TNFα, CD4+ T cells expressing high levels of TNFα and IFNγ, as well as CD8+ T-cells expressing TNFα, IFNγ and GranzymeB. NK cells expressed Granzyme B, high levels of TNFα and dim levels of IFNγ. Comparison of all activated immune cells across treatment groups revealed very high levels of activated cells in NDV/VEGF-C group, with more than 16% of all immune cells in tumors being activated ( FIGS.  16 D and  16 E ). The main subset of activated cells was CD8+ T-cells, comprising more than 70% of all activated cells, followed by CD4 − CD8 −  T-cells, CD4+ T-cells and NK cells ( FIG.  16 F ). Taken together, these data show high activation status of CD8, CD4 and NK cells driven by combination of VEGF-C and NDV effects in tumors. Immune cell activation status was greatly heightened with VEGF-C in comparison to NDV treatment alone. 
     6.5.2.3 Enrichment of T-Cells and Dendritic Cells Tumors Expressing VEGF-C and Treated with NDV is Associated with Expansion of Lymphatic Vessels 
     In agreement with the results obtained with flow cytometry, immunostaining of primary tumors demonstrated high density of CD8+ T-cells in NDV/VEGF-C tumors. CD4+ T-cells were also enriched, however, to a lesser extent than CD8+ T-cells. Analysis of myeloid cells in tumor showed particularly high densities of CD11c+ dendritic cells in NDV/VEGF-C tumors ( FIGS.  17 A- 17 D ). Lymphatic vessels were prominent intratumorally and in particular peritumorally only in VEGF-C expressing tumors. Remarkably, a tight association between CD8+ T-cells and lymphatic vessels was observed ( FIGS.  17 G- 171   ). Quantification of immunostained tumors showed a greater increase of CD8+ T-cells in tumor expressing VEGF-C and treated with NDV in comparison to tumors lacking VEGF-C ( FIG.  17 J ). Conventional flow cytometry confirmed striking increase in effector memory T-cells in NDV/VEGF-C. Quantitative analysis of tumor vasculature showed increased lymphatic vessel densities in NDV/VEGF-C group and indicated that NDV alone was not driving lymphangiogenesis. All B16F10 tumors were highly vascularized and NDV/VEGF-C group in fact showed lower density of blood vessels compared to all other treatment groups. Taken together, these data demonstrate striking enrichment of CD8, CD4 and CD11c+ dendritic cells associated with tumor lymphatic vessels in NDV/VEGF-C-treated tumors. 
     6.5.2.4 Immunophenotyping of Sentinel and Contra-Lateral Lymph Nodes Reveals Changes in Immune Cell Subsets Unique for NDV/VEGF-C Tumors 
     Numerous changes in immune cell phenotypes were observed in both, sentinel and contralateral lymph nodes in NDV/VEGF-C group compared to NDV alone and to non-treated groups ( FIGS.  18 A- 18 D ). In particular, in sentinel lymph nodes an increase in CD4+ and CD8+ T cells expressing CD83 and/or CD86 has been noted, which typically indicates activated subsets. Interestingly, one subset unique to the NDV/VEGF-C group has CD103 (CD103+ CD44+ CD49b+ CD86+ CD4 T cells), and likely represents a tumor-specific subset ( FIG.  18 A ). Contralateral lymph nodes do not drain tumor directly and changes of immune cells are a result of systemic changes, rather than a regional response to a tumor. Remarkably, several subsets highly enriched in contralateral lymph nodes in NDV/VEGF-C group, including CD83+ CD4 T cells, tumor-specific CD103+ CD83+ CD86+ CD8 T cells and CD83+ CD86+ Ly6c+ CD8 T cells were observed ( FIG.  18 B ). Taken together, these data indicate that the NDV/VEGF-C combination leads to a potent immune activation of unique immune cell subsets both regionally (in sentinel lymph nodes) and systemically (in contralateral lymph nodes) that is strongly associated with tumor eradication. 
     6.6 Example 6: Construction of a Recombinant APMV4 Encoding a Codon Optimized hVEGF-C Gene 
     A new transcription unit is inserted at the restriction site Sal I that is created at the intergenic region between the viral genes P and M in the rescue plasmid pAPMV4 (see SEQ ID NO: 90 for plasmid pRz-APMV4 sequence without the additional transcription unit that is in bold). The DNA insert will be obtained by PCR, using as template a plasmid containing a codon optimized sequence encoding the human VEGF-C protein (SEQ ID NO: 35). The PCR primers are designed to introduce all the features required to generate a functional APMV4 transcription unit: The forward primer introduces the restriction site Sal I, the gene end sequence (transcription termination signal) from the viral gene HN, an intergenic sequence (1 nucleotide T), the gene start sequence (transcription initiation signal) from the viral gene HN and the Kozac sequence for efficient translation. The reverse primer introduces additional nucleotides as needed to comply with the rule of six, and a restriction site Sal I. The insert is cloned into the Sal I site of the rescue plasmid pAPMV4 by the technique In Fusion (GeneArt Seamless PLUS Cloning and Assembly Kit (ThermoFisher Scientific)). 
     Inserts containing a point mutation in the human VEGF-C sequence are generated as described above but two overlapping PCR products are generated: the first PCR product covers the sequence from the 5′ end of the transcription unit to the point mutation. The reverse primer contains the mutated sequence. The second PCR product covers the sequence from the point mutation to the 3′ end of the transcription unit and overlaps with the first PCR product by 15 nucleotides. The forward primer for the second PCR also contains the mutated sequence. Both PCR products are cloned into the Sal I site of the rescue plasmid pAPMV4 by the technique In Fusion. Two different point mutants are created: Cys156Ser and Cys137Ala. 
     Transcription units encoding the mature version of the human VEGF-C protein (delta N delta C), with or without point mutations, are created using the rescue plasmids containing the full length inserts described above (with and without point mutations, respectively) as templates. Two overlapping PCR products are created: the first PCR product contains the Sal I restriction site and APMV regulatory sequences described above and the signal sequence from an Immunoglobulin light chain (a potent signal peptide for protein secretion; SEQ ID NO: 25). The template is a plasmid that contains the sequence of the light chain signal peptide. The second PCR product overlaps in 15 nucleotides and contains the sequence encoding the mature form of the hVEGF-C (delta N delta C), followed by additional nucleotides as needed to comply with the rule of six, and a restriction site Sal I. The template for the second PCR is the rescue plasmid containing the full length, codon optimized sequence of the hVEGF-C protein, with or without the point mutations Cys156Ser or Cys137Ala. 
     All the constructs are confirmed by sequencing of the full length of the inserted sequences. 
     The invention is not to be limited in scope by the specific embodiments described herein. Indeed, various modifications of the invention in addition to those described will become apparent to those skilled in the art from the foregoing description and accompanying Figures. Such modifications are intended to fall within the scope of the appended claims. 
     All references cited herein are incorporated herein by reference in their entirety and for all purposes to the same extent as if each individual publication or patent or patent application was specifically and individually indicated to be incorporated by reference in its entirety for all purposes.