Abstract:
The patent application PCT/EP02/01867 (WO 02/066629) “Recombinant vector containing infectious human cytomegalovirus genome with preserved wild-type characteristics of clinical isolates” describes the cloning of a leukotropic and endothelial cell tropic clinical isolate of human cytomegalovirus (HCMV) as a bacterial artificial chromosome (BAC) in  E. coli . The cloned wild-type genome of HCMV was designated FIX-BAC (Fusion-Inducing-Factor-X)-BAC (Hahn, Khan et al., 2002). The patent application PCT/EP02/01867 (WO 02/066629) also describes the construction of virus mutants using FIX-BAC technology and subsequent phenotypical testing of virus mutants for loss of wild-type features such as leukocyte and endothelial cell tropism. The genetic determinants of endothelial cell and leukocyte tropism were assigned to the UL132-UL128 genetic locus of HCMV. Moreover, the patent application PCT/EP02/01867 (WO 02/066629) describes novel transcripts within the UL131-UL128 genetic locus which are differentially spliced. The current patent application describes in more detail the UL131-128 transcripts of clinical isolates of HCMV. Translation of the newly identified transcripts showed novel open reading frames (orfs) coding for novel putative C×C and CC chemokines which are of crucial importance for HCMV pathogenesis and tissue tropism.

Description:
DESCRIPTION  
         [0001]    The previous patent application PCT/EP02/01867 (WO 02/066629) describes the cloning of FIX-BAC and assigned the genetic determinants of leukocyte and endothelial cell tropism of HCMV to the UL132-UL128 genetic locus of HCMV.  
           [0002]    In the current patent application specific virus mutants targeting individual genes within the UL131-128 region as well as at the borders of UL131-128 were constructed using a sited-directed PCR-based approach in  E. coli . Recombination functions of bacteriophage λ (α/β/γ) were transiently provided on a plasmid in  E. coli  DH10B containing at least one copy of the FIX-BAC genome. The recombination fragment was generated by PCR over a kanamycin resistance marker (pACYC177, NEB Biolabs).  
           [0003]    The following primers were used:  
                                       RVFIXΔUL130-132   (P-132-for:   5′-AAA CCA CGT CCT CGT CAC ACG TCG TTC GCG GAC ATA GCA AGA;   [SEQ. ID NO: 1]                   AAT CCA CGT CGC CAC ATC TCG AGA CGA TTT ATT CAA CAA AGC CAC               G-3′           P-130-rev:   5′-AAC GGC GTC AGG TCT TTG GGA CTC ATG ACG CGC GGT TTT CAA;   [SEQ. ID NO: 2]               AAT TCC CTG CGC GCG CGA CGG GCG CCA GTG TTA CAA CCA ATT AAC               C-3′)               RVFIXΔUL130   (P-130-for:   5′-GCG CCA CAC GCC CGG AGC CTC GAG TTC AGC GTG CGG CTC TTT;   [SEQ. ID NO: 3]               GCC AAC TAG CCT GCG TCA CGG CGA TTT ATT CAA CAA AGC-3′           P-130-rev:   5′-AAC GGC GTC AGG TCT TTG GGA CTC ATG ACG CGC GGT TTT CAA;   [SEQ. ID NO: 4)               AAT TCC CTG CGC GCG CGA CGG GCG CCA GTG TTA CAA CCA ATT AAC               C-3′               RVFIXΔ128K   (P-128-for-kons:   5′-TGC GTT CTG TGG TGC GTC TGG ATC TGT CTC TCG ACG TTT CTG,   [SEQ. ID NO: 5]               ATA GCC ATG TTC CAT CGA CGA TTT ATT CAA CAA AGC CAC G-3′           P-128-kons2:   5′-CGG CAC ACA TCC AGC CGT TTG TGT TTC TTA ACG CTC TCC AGG   [SEQ. ID NO: 6])               TAC TGA TCC AGG CCC ACG GCC AGT GTT ACA ACC AAT TAA-3′               RVFIXΔUL127   (P-127-for:   5′-TTG AGA TTT CTG TCG CCG ACT AAA TTC ATG TCG CGC GAT AGT,   [SEQ. ID NO: 7]               GGT GTT TAT CGC CGA TAG CGA TTT ATT CAA CAA AGC CAC-G3′           P-127-rev:   5′-AAT ATT GAT TTA CGC TAT ATA ACC AAT GAC TAA TAT GGC TAA;   [SEQ. ID NO: 8]               TGG CCA ATA TTG ATG CAA GCC AGT GTT ACA ACC AAT TAA-3′)               RVFIXΔUL148   (P-148-for:   5′-GAC TAT GTG CAT GTT CGG CTA CTG AGC TAC CGA GGC GAC CCC,   [SEQ. ID NO: 9]               CTG GTC TTC AAG CAC ACT CGA TTT ATT CAA CAA AGC CAC-3′           P-148-rev:   5′-CAC CAG GTA GGT TAT CAA AAC GCG AGC CCA TAT CGC CGC CAT;   [SEQ. ID NO: 10)               CAT TGT AAT CAG CAA TGT GCC AGT GTT ACA ACC AAT TAA-3′               RVFIXΔUL132K   (P-132-forK:   5′-ACG TCC TCG TCA CAC GTC GTT CGC GGA CAT AGC AAG AAA TTC,   [SEQ. ID NO: 11]               ACG TCG CCA CGT CTC GAG ACG ATT TAT TCA ACA AAG CCA-3′           P-132-revk:   5′-AAG GTT CTT CCA TTT CCG AGG CGG TCA GTT CAT CGT ACA CCG;   [SEQ. ID NO: 12])               AGA CGT AGT ACC TGA TGG GGC CAG TGT TAC AAC CAA TTA ACC-3′               RVFIXΔUL132-128   (P-131-for:   5′-TGT CTT TCG GTT CCA ACT CTT TCC CCG CCC CAT CAC CTC GCC;   [SEQ. ID NO: 13]               TGT ACT ATG TGT CGA TTT ATT CAA CAA AGC CAC G-3′           P-128-rev:   5′-TCG CGC GAC ATG AAT TTA GTC GGC GAC AGA AAT CTC GAA ACG;   [SEQ. ID NO: 14])               CGT ATT TCG GAC AAA CAC ACA TGC CAG TGT TAC AAC CAA TTA               ACC-3′               RVFIXΔUL133-148   (P-133-for:   5′-CGC TGT AGG GAT AAA TAG TGC GAT GGC GTT TGT GGG AGA ACG,   [SEQ. ID NO: 15]               CAG TAG CGA TGG GTT GCG ACG TGC ACC GAT TTA TTC AAC AAA GCC               ACG-3′           P-148-rev:   5′-CAC CAG GTA GGT TAT CAA AAC GCG AGC CCA TAT CGC CGC CAT;   [SEQ. ID NO: 16]               CAT TGT AAT CAG CAA TGT GCC AGT GTT ACA ACC AAT TAA-3′)               RVFIXΔUL131K   (P-131-fork:   5′-CAG TCT GCA ACA TGC GGC TGT GCT GGG TGT GGC TGT CTG TTT,   [SEQ. ID NO: 17]               GTC TGT GCG CCG TGG TGC CGA TTT ATT CAA CAA AGC CAC-3′           P-131-rev:   5′-GCT AGT TGG CAA AGA GCC GCA CGC TGA ACT CGA GGC TCC GGG;   [SEQ. ID NO: 18]               CGT GTG GCG GCC AGT GTT ACA ACC AAT TAA CC-3′)               RVFIXΔ146-147   (P-UL146-for:   5′-GAT TTT CCG GGA ATA CCG GAT ATT ACG AAT TAC TGG TAG TGA,   [SEQ. ID NO: 19]               CGT AGA TAA TAA AAT TAT ACG ATT TAT TCA ACA AAG CCA CG-3′           P-UL147-rev:   5′-CAC CAA AGC CGT TAG CGT GCC CAG AGC TAC CGC ACG GTA AAA.   [SEQ. ID NO: 20]               TAG GGA CAT GAG CCA GTG TTA CAA CCA ATT AAC C-3′)          
 
           [0004]    The Southern Blot was probed with the kanamycin specific probe pAcyc. The generation and testing of the mutants is described in the text. M: molecualr weight marker 1 kb ladder.  
           [0005]    Tabel 1 summarizes the phenotypical testing of RVFIX virus mutants.  
                                 TABLE 1                           Leukocyte, Monocyte and HUVEC tropism                PMNL-Tropism   MO-Tropism   HUVEC-Tropism               RVFIX WT   positive   positive   HUVEC+       RVFIX  Δ UL130   negative   negative   HUVEC−       RVFIX  Δ UL131   negative   negative   HUVEC−       RVFIX  Δ UL132   positive   positive   HUVEC+       RVFIX  Δ UL128   negative   negative   HUVEC−       RVFIX Δ UL131-128   negative   negative   HUVEC−       RVFIX Δ UL127   positive   positive   HUVEC+       RVFIX Δ UL148   positive   positive   HUVEC+       RVFIX Δ UL133-148   weak pos.   positive   HUVEC+       RVFIX Δ UL146-147   weak pos.   positive   HUVEC+                                          
 
           [0006]    Only mutants with a deletion of either individual genes UL131, UL130, UL128 or the entire UL131-128 locus lost tropism for both endothelial cells and leukocytes. When genes next to UL131-128 were deleted (UL132, UL127 or UL148) the virus mutants were perfectly capable of infecting endothelial cells and leukocytes confirming the UL131-128 locus as the genetic determinant of endothelial cell and leukocyte tropism. When a deletion between UL133-148 was introduced into the RVFIX genome the resulting virus RVFIXΔUL133-148 retained the capability to infect endothelial cells and leukocytes, however a predominant monocyte tropism was observed. Since it is known from literature (Penfold, Dairaghi et al., 1999; Mocarski, Jr., 2002) that UL146 is a functional C×C chemokine, the predominant monocyte tropism of the virus mutant RVFIXΔUL133-148 was attributed to the loss of UL146. In order to confirm this notion, a virus mutant was constructed which UL146-UL147 was deleted. The virus mutant RVFIXΔ146-147 confirmed the RVFIXΔUL133-148 phenotype.  
           [0007]    The role of leukocyte attraction in cytomegalovirus infection was recently underscored by the finding that, in MCMV, two differentially spliced CC chemokine homologs (Fleming, Davis-Poynter et al., 1999; MacDonald, Li et al., 1997; MacDonald, Burney et al., 1999) encoded by m131-129 (MCK-1 and MCK-2) are important determinants of virus dissemination (MacDonald, Li, &amp; Virgin, 1997; MacDonald, Burney, Resnick, &amp; Virgin, IV, 1999; Saederup, Lin et al., 1999; Saederup, Aguirre et al., 2001), acting as proinflammatory signals that recruit leukocytes to the site of infection to increase virus spreading. The relevance of chemoattraction is highlighted in this study by the phenotype of mutants RVΔUL146-147 and RVΔUL133-148, both bearing a functional UL131-128 locus while lacking the viral C×C chemokine genes UL146-147. UL146 product is a potent attractor and activator of human PMNL in vitro (Penfold, Dairaghi, Duke, Saederup, Mocarski, Kemble, &amp; Schall, 1999). The mentioned virus mutants RVΔUL146-147 and RVΔUL133-148 share a full endothelial cell and monocyte tropism, but are only inefficiently transmitted to PMNL (polymorphonuclear leukocytes). These results suggest that genes within UL131-128 are sufficient both for local endothelial spread and for attraction of (and virus passage to) monocytes, while the additional chemotactic factors encoded by UL146-147 enhance virus dissemination by attracting PMNL and favouring their infection. The chemotactic activity of each individual gene product of the UL131-128 locus, as well as the cooperation with other viral or cellular gene signalling molecules, remain to be further elucidated. 
       
    
    
       [0008]    As described in patent application PCT/EP02/01867 (WO 02/066629) 5′ and 3′ RACE analyses had led to the identification of novel viral transcripts running through the genetic locus UL131-UL128 with a start codon at the beginning of UL131 and a stop codon and poly A signal at the end of UL128. The current patent application provides a more in depth analysis of the newly identified transcripts on the transcriptional and translational level. FIG. 4A-C showes a sequence comparison of the newly identified RACE clones 95-3, 95-8 and 95-11 to FIX-BAC genomic sequence. FIG. 5 shows the entire UL131-128 genetic locus and predicted individual genes.  
         [0009]    Transcript analysis was performed by rapid amplification of cDNA ends (RACE). First strand cDNA synthesis and rapid amplification of cDNA ends (RACE) was performed using the SMART™ RACE cDNA amplification kit (Clontech) according to the manufacturer&#39;s instructions. RACE products were cloned into the pT-Adv vector (Clontech) using the AdvanTAge™ PCR cloning kit for analysis and sequencing. For rapid ampification of cDNA ends (RACE) from the 5′ RACE cDNA sample the following primers were used: primer 57-GSP1: 5′-CGG CAC ACA TCC AGC CGT TTG TGT TTC TTA 3′ [SEQ. ID NO: 35]; primer 72-GSP1: 5′-TAA CGC TCT CCA GGT ACT GAT CCA GGC CCA-3′ [SEQ. ID NO: 36]; primer 73-GSP1: 5′-TCG TCA GTT TGT TGT GTA CGA CCT GGC GTG-3′ [SEQ. ID NO: 37]; primer 74-GSP1: 5′-TAT TGG CCT CGG TGA ACG TCA ATC GCA CCT -3′ [SEQ. ID NO: 38]. For rapid ampification of cDNA ends from the 3′ RACE cDNA sample the following primers were used: primer 56-GSP2: 5′-TGT GTC GGG TGT GGC TGT CTG TTT GTC TGT-3′ [SEQ. ID NO: 39]; primer 75-GSP2: 5′-TCT GCT TCG TCA CCA CTT TCA CTG CCT GCT-3′ [SEQ. ID NO: 40]; primer 76-GSP2: 5′-CGC AGA AGA ATG TTG CGA ATT CAT AAA CGT-3′ [SEQ. ID NO: 41]; primer 77-GSP2: 5′-GCT GCG GTG TCC GGA CGG CGA AGT CTG CTA-3′ [SEQ. ID NO: 42]; primer 78-GSP2: 5′-CCA GCT GGC AGA TTC CCA AAC TAA TGA AAG-3′ [SEQ. ID NO: 43]; primer 93-GSP2: 5′-CTT TCG GTT CCA ACT CTT TCC CCG CCC CAT-3′ [SEQ. ID NO: 44]; primer 94-GSP2: 5° CAC CTC GCC TAT ACT ATG TGT ATG ATG TCT-3′ [SEQ. ID NO: 45]; primer 95-GSP2: 5′-CTC TCT TTC TCA GTC TGC AAC ATG CGG CTG-3′ [SEQ. ID NO: 46]; primer 96-GSP2: 5′-GTT GTC CAA GCC GTC GCT CGC ATC GTA GTG-3′ [SEQ. ID NO: 47]; primer 97-GSP2: 5′-CAT AAT AAA GCT CTC TTT CTC AGT CTG CAA-3′ [SEQ. ID NO: 48]; primer 98-GSP2: 5′-TAT GAT GTC TCA TAA TAA AGC TCT CTT TCT-3′ [SEQ. ID NO: 49].  
         [0010]    Identification of Novel Tropism Determining Transcripts  
         [0011]    The novel and previously unrecognized transcripts running through the entire UL131-128 region with a predicted UL131 start codon (nt 176825-176823 according to (Chee, Bankier, Beck, Bohni, Brown, Cerny, Horsnell, Hutchison, 111, Kouzarides, Martignetti, &amp; ., 1990), and a UL128 stop codon (nt 174865-174863) were identified. The newly identified transcripts show a splicing event between UL128×2 and UL128×3 (nt 175201-175081), either exclusively or in conjunction with splicing between UL131×1 and UL131×2 (nt 176589-176480). An additional splicing event between UL128×1 and UL128×2 (nt 175459-175335) was observed in several clones.  
         [0012]    3′ RACE analysis consistently identified a single polyA stretch 14±1 nucleotides 3′ to the canonical AATAAA polyA signal immediately downstream of the UL128 stop codon.  
         [0013]    As depicted in FIG. 6 [HCK-1:nucleic acid:SEQ. ID NO: 50; amino acid: SEQ. ID NO. 51, HCK-2:nucleic acid: SEQ. ID NO: 52; amino acid: SEQ. ID NO: 53] and translation of RACE clone 95-3 (FIG. 9) [FIX:nucleic acid:SEQ. ID NO: 54; 95-3:nucleic acid:SEQ. ID NO: 55; HCK-1 nucleic acid:SEQ. ID NO: 56;amino acid:SEQ. ID NO: 57] and RACE clone 95-8 (FIG. 10) [FIX: nucleic acid:SEQ. ID NO: 58; 95-8:nucleic acid:SEQ. ID NO: 58; HCK-2:nucleic acid:SEQ. ID NO: 60; amino acid:SEQ. ID NO: 61] shows predicted proteins with a C×C motif (red) which is characteristic for C×C chemokines. RACE clone 95-3 encodes a 129 aa protein designated HCK-1 (pUL131; about 15 kDA) and RACE clone 95-8 encodes a 79 aa protein designated HCK-2 (pUL131×1; about 9 kDA). Both proteins show a number of N-linked glycosilation sides.  
         [0014]    Both newly indentified transcripts (RACE clone 95-3 and RACE clone 95-8) have a splice between UL128×1 and UL128×2. RACE clone 95-3 has an additional splice between UL131×1 and UL131×2 which is absent in RACE clone 95-8. Sequence comparsion between the RACE clones, FIX-BAC and AD169 genomic sequences revealed that a stretch of 7×nt A (blue) in UL131 of FIX-BAC and the RACE clones 95-3 and 95-8 is extended to a stretch of 8×nt A (blue) in AD169 genomic sequence. Translation of the RACE clones 95-3 (FIG. 9) and 95-8 (FIG. 10) showed an open reading frame (ORF) with a conserved C×C C C chemokine motif (red) in FIX-BAC which is destroyed by the extension of 7×nt A to 8×nt A in the fibroblast adapted laboratory strain AD169. In RACE clone 95-3 the splice between UL131×1 and UL131×2 removes the stop codon at the end of UL131×1 and codes for a putative 129 aa C×C chemokine like protein (designated HCK-1; Human cytomegalovirus chemokine like protein), whereas in RACE clone 95-8 the stop codon at the end of UL131×1 is used to truncate the C×C chemokine like protein HCK-2 to 79 aa.  
         [0015]    Putative CC chemokine like proteins designated HCK-3 and HCK-4 are encoded by the predicted UL128 ORF (FIG. 7) [HCK-3:nucleic acid:SEQ. ID NO: 62; amino acid:SEQ. ID NO: 63; HCK-4:nucleic acid:SEQ. ID NO: 64; amino acid:SEQ. ID NO: 65]. However, RACE analyses have not yet fully confirmed the 5′ start of these transcripts. HCK-3 (pUL128×1) (FIG. 12) [FIX:nucleic acid:SEQ. ID NO: 66; 128B:nucleic acid:SEQ. ID NO: 67; HCK-3:nucleic acid:SEQ. ID NO: 68; amino acid:SEQ. ID NO: 69]is a 59 aa protein (about 7 kDA) and HCK-4 (pUL128) (FIG. 13) [FIX:nucleic acid:SEQ. ID NO: 70; 128A:nucleic acid:SEQ. ID NO: 71; HCK-4:nucleic acid:SEQ. ID NO: 72; amino acid:SEQ. ID NO: 73] is a 171 aa protein (about 20 kDA). Splicing events between UL128×1, UL128×2 and UL128×3 fuse the three UL128 exons to form the 171 aa protein HCK-4. In case of HCK-3 the splice between UL128×1 and UL128×2 is absent and thus the TGA stop codon at the end of UL128×1 truncates the protein HCK-3 to 59 aa.  
         [0016]    RACE clone 95-11 (FIG. 11) [FIX:SEQ. ID NO: 74; 95-11:S EQ. ID NO: 75] confirms that UL128 is composed of three exons.  
         [0017]    Interestingly, in RACE clone 95-11 the stretch of 7×nt A (present in RACE clones 95-3 and 95-8) is extended to a stretch of 9×nt A. This extension from 7× to 9×nt A destroys the C×C motif in RACE clone 95-11 and takes the predicted HCK-1 and HCK-2 proteins out of frame. It can be speculated that by increasing or decreasing the numbers of nt (for example nt A, nt T, nt G or nt C) in a given transcript, HCMV has found a way of transcriptional regulation of tissue tropism. It can be pictured that in a given cell type (for example fibroblasts) predominantly one transcript (for example 95-11) is synthesized over others (for example 95-8 or 95-3), thereby introducing a frame shift in an open reading frame (for example HCK-1 and HCK-2) whose product is necessary for tissue specific infection. It can also be pictured that in other cells for example endothelial cells, monocytes, leukocytes, dendritic cells or progenitor cells predominantly those transcripts are made (for example 95-3, 95-8, 128A and 128B) whose protein products (for example HCK-1, HCK-2, HCK-3 and HCK-4) encode viral chemokines and microfusion inducing factors (for example UL130, HCK-5) (FIG. 14) [nucleic acid:SEQ. ID NO: 76; amino acid:SEQ. ID NO: 77].  
         [0018]    Closer analysis of the newly encoded proteins HCK-1 and HCK-2 shows that they have N-linked gylcosilation sites. It can be speculated that HCK-1 may be membrane bound and is trafficking through the endoplasmatic reticulum. This membrane bound HCK-1 could be of crucial importance for inducing the microfusion event (in conjunction with pUL130, HCK-5) between endothelial cells and leukocytes, monocytes, makrophages and dendritic cells or possibly other cell types. It can be assumed that HCK-2 may be a soluble chemokine which would be necessary to attract leukocytes (in conjunction with the C×C chemokines UL146 and UL147) to the site of infection. Thus HCK-1 and HCK-2 are major pathogenicity factors for virus dissemination in vivo and in vitro. It can further be assumed that the newly identified CC chemokines HCK-3 and HCK-4 may attract monocytes, macrophages, dendritic cells and possibly hematopoietic progenitor cells or stem cells to the site of infection and that concomitantly the infectious virus is spread via microfusion possibly by the use of HCK-1 and HCK-5 protein products. It can be pictured that chemokine receptors interact with the HCK-1, HCK-2, HCK-3, HCK-4 and HCK-5 protein and that the microfusion event occurs via receptor internalisation. Adhesion molecules which are upregulated by HCMV infection may provide assistance in the attachment, recruitment and microfusion process.  
         [0019]    Transcript Analyses by Northern Blot  
         [0020]    Northern blots from fibroblasts infected with RVFIX (FIG. 8), when hybridized with a UL131-128 specific probe, showed an upper (2.0-1.8 kb) band and a lower (0.8-0.7 kb) band. The 0.8-0.7 kb band can be interpreted as a UL128-specific transcript, the 2.0-1.8 kb band as the long UL131-128 encompassing transcript. Independent promoters may drive each transcript, one predicted upstream of the UL131 gene and the other within the UL131-130 region. The lack of a UL130 specific transcript suggests that the UL130 protein may be translated from the polycistronic 2.0-1.8 kb mRNAs through either translational reinitiation or an IRES-like mechanism.  
         [0021]    Northern analyses of RVFIXΔUL130 or RVFIXΔUL131K infected fibroblasts shows that following the kan R  cassette insertion into either UL131 or UL130 the stability of all transcripts of the UL131-128 region was altered (2.0-1.8 kb transcript was absent and 0.8-0.7 kb transcript was strongly diminished), whereas kan R  insertion into RVFIXΔUL128 shifted both transcripts (FIG. 8). In Toledo infected cells both mRNA bands are missing as a consequence of truncation of UL128 and dislocation of the polyA signal (FIG. 8). Taken together, these data suggest that a targeted deletion of individual genes within UL131 to UL128 affects the stability of transcripts of the entire locus. Functionally, the lack of endothelial cell and leukocyte tropism observed in Toledo may correlate with the failure to express all UL131-128 transcripts. In contrast, point mutations in the UL131-128 region of the laboratory strain AD169 as compared to RVFIX neither affect mRNA mobility nor stability. However, in AD169 a stretch of 7×nt A in RVFIX is extended to 8×nt A in laboratory strain AD169. As a result, the ORF of pUL131 (HCK-1) and pUL131×1 (HCK-2) in AD169 is frameshifted.  
         [0022]    By construction of individual virus mutants which delete individual genes UL131, UL130, UL128 it could be demonstrated that HCMV loses its tropism for monocytes, leukocytes and endothelial cells when the genetic region coding for the viral proteins HCK-1, HCK-2, HCK-3, HCK-4 or HCK-5 is removed from the virus genome. It is reasonable to assume that infection of cell types such as dendritic cells, macrophages, progenitor cells, B- and T-lymphocytes, hematopietic stem cells may occur in the same fashion and that the UL131-128 locus of HCMV and its encoded protein products described are indispensable for the infection process in vivo and in vitro.  
         [0023]    Rescue of Leukotropism and Endothelial Cell Tropism by Ectopic Reinsertion of the ULI31-128 Region of FIX-BAC into the Laboratory Strain AD169.  
         [0024]    In order to show that the UL131-128 region of FIX-BAC is sufficient to rescue tissue tropism of a an endothelial cell tropism and leukotropism incompetent strain, the UL131-128 genetic locus of FIX-BAC was cloned into the vector pOR16K-zeo next to an FRT site. In AD169-BAC the UL40 region was deleted and replaced with a kanamycin cassette flanked by FRT sites (from plasmid pcp015). Subsequently the kanamycin resistance marker was removed by flip recombinase (provided by plasmid pcp20) in  E. coli . Ectopic insertion of the UL131-128 region from FIX-BAC (cloned into pORI6K-zeo) into AD169ΔUL40FRT-BAC was achieved by flip recombinase in  E. coli  and selection for kan R  and zeo R  resistant clones. The reconstituted virus RVAD169ΔUL40+UL131-128 could infect endothelial cells and leukocytes. However, the leukocyte tropism was predominantly restricted to monocytes, as expected in a virus which lacks the C×C chemokine coding genes UL146 and UL147.  
         [0025]    The genes UL131, UL130, UL128 and the protein products with novel structure encoded (namely HCK-1, HCK-2, HCK-3, HCK-4 and HCK-5) are of fundamental importance for infection, dissemination and spread of HCMV in the human body. It can be pictured that these genes and proteins are key players in disease conditions such as vascular disease and atherosclerosis development. They are targets for drug design (small molecules, anti-sense RNA, siRNAs), anti-viral chemotherapy, vaccine development and gene therapy against HCMV and other virus induced diseases (for example HIV), as well as diseases such as cancer, autoimmune disorders and atherosclerosis. Since viruses like HCMV co-evolved with the host during human evolution it, is reasonable to assume that the newly described C×C and CC chemokines of novel structure may have as yet unidentified chemokine homologues in humans (for example secreted by human immune cells).  
         [0026]    Reference List  
         [0027]    Chee, M. S., Bankier, A. T., Beck, S., Bohni, R., Brown, C. M., Cerny, R., Horsnell, T., Hutchison, C. A., III, Kouzarides, T., Martignetti, J. A., and . (1990). Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169.  Curr Top Microbiol Immunol  154, 125-169.  
         [0028]    Fleming, P., Davis-Poynter, N., Degli-Esposti, M., Densley, E., Papadimitriou, J., Shellam, G., and Farrell, H. (1999). The murine cytomegalovirus chemokine homolog, m131/129, is a determinant of viral pathogenicity.  J Virol  73, 6800-6809.  
         [0029]    Hahn, G., Khan, H., Baldanti, F., Koszinowski, U. H., Revello, M. G., and Gerna, G. (2002). The human cytomegalovirus ribonucleotide reductase homolog UL45 is dispensable for growth in endothelial cells, as determined by a BAC-cloned clinical isolate of human cytomegalovirus with preserved wild-type characteristics.  J Virol  76, 9551-9555.  
         [0030]    MacDonald, M. R., Burney, M. W., Resnick, S. B., and Virgin, H. W., IV (1999). Spliced mRNA encoding the murine cytomegalovirus chemokine homolog predicts a beta chemokine of novel structure.  J Virol  73, 3682-3691.  
         [0031]    MacDonald, M. R., Li, X. Y., and Virgin, H. W. (1997). Late expression of a beta chemokine homolog by murine cytomegalovirus.  J Virol  71, 1671-1678.  
         [0032]    Mocarski, E. S., Jr. (2002). Immunomodulation by cytomegaloviruses: manipulative strategies beyond evasion.  Trends Microbiol  10, 332-339.  
         [0033]    Penfold, M. E., Dairaghi, D. J., Duke, G. M., Saederup, N., Mocarski, E. S., Kemble, G. W., and Schall, T. J. (1999). Cytomegalovirus encodes a potent alpha chemokine.  Proc Natl Acad Sci U S A  96, 9839-9844.  
         [0034]    Saederup, N., Aguirre, S. A., Sparer, T. E., Bouley, D. M., and Mocarski, E. S. (2001). Murine cytomegalovirus CC chemokine homolog MCK-2 (m131-129) is a determinant of dissemination that increases inflammation at initial sites of infection.  J Virol  75, 9966-9976.  
         [0035]    Saederup, N., Lin, Y. C., Dairaghi, D. J., Schall, T. J., and Mocarski, E. S. (1999). Cytomegalovirus-encoded beta chemokine promotes monocyte-associated viremia in the host.  Proc Natl Acad Sci U S A  96, 10881-10886.  
     
       
       
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aaaccacgtc ctcgtcacac gtcgttcgcg gacatagcaa gaaatccacg tcgccacatc     60 

tcgagacgat ttattcaaca aagccacg                                        88 

 
           
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               oligonucleotide primer  
             
           
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aacggcgtca ggtctttggg actcatgacg cgcggttttc aaaattccct gcgcgcgcga     60 

cgggcgccag tgttacaacc aattaacc                                        88 

 
           
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               oligonucleotide primer  
             
           
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gcgccacacg cccggagcct cgagttcagc gtgcggctct ttgccaacta gcctgcgtca     60 

cggcgattta ttcaacaaag c                                               81 

 
           
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aacggcgtca ggtctttggg actcatgacg cgcggttttc aaaattccct gcgcgcgcga     60 

cgggcgccag tgttacaacc aattaacc                                        88 

 
           
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            5 

tgcgttctgt ggtgcgtctg gatctgtctc tcgacgtttc tgatagccat gttccatcga     60 

cgatttattc aacaaagcca cg                                              82 

 
           
             6  
             81  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            6 

cggcacacat ccagccgttt gtgtttctta acgctctcca ggtactgatc caggcccacg     60 

gccagtgtta caaccaatta a                                               81 

 
           
             7  
             81  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            7 

ttgagatttc tgtcgccgac taaattcatg tcgcgcgata gtggtgttta tcgccgatag     60 

cgatttattc aacaaagcca c                                               81 

 
           
             8  
             81  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            8 

aatattgatt tacgctatat aaccaatgac taatatggct aatggccaat attgatgcaa     60 

gccagtgtta caaccaatta a                                               81 

 
           
             9  
             81  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            9 

gactatgtgc atgttcggct actgagctac cgaggcgacc ccctggtctt caagcacact     60 

cgatttattc aacaaagcca c                                               81 

 
           
             10  
             81  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            10 

caccaggtag gttatcaaaa cgcgagccca tatcgccgcc atcattgtaa tcagcaatgt     60 

gccagtgtta caaccaatta a                                               81 

 
           
             11  
             81  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            11 

acgtcctcgt cacacgtcgt tcgcggacat agcaagaaat tcacgtcgcc acgtctcgag     60 

acgatttatt caacaaagcc a                                               81 

 
           
             12  
             84  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            12 

aaggttcttc catttccgag gcggtcagtt catcgtacac cgagacgtag tacctgatgg     60 

ggccagtgtt acaaccaatt aacc                                            84 

 
           
             13  
             76  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            13 

tgtctttcgg ttccaactct ttccccgccc catcacctcg cctgtactat gtgtcgattt     60 

attcaacaaa gccacg                                                     76 

 
           
             14  
             87  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            14 

tcgcgcgaca tgaatttagt cggcgacaga aatctcgaaa cgcgtatttc ggacaaacac     60 

acatgccagt gttacaacca attaacc                                         87 

 
           
             15  
             90  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            15 

cgctgtaggg ataaatagtg cgatggcgtt tgtgggagaa cgcagtagcg atgggttgcg     60 

acgtgcaccg atttattcaa caaagccacg                                      90 

 
           
             16  
             81  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            16 

caccaggtag gttatcaaaa cgcgagccca tatcgccgcc atcattgtaa tcagcaatgt     60 

gccagtgtta caaccaatta a                                               81 

 
           
             17  
             81  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            17 

cagtctgcaa catgcggctg tgctgggtgt ggctgtctgt ttgtctgtgc gccgtggtgc     60 

cgatttattc aacaaagcca c                                               81 

 
           
             18  
             74  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            18 

gctagttggc aaagagccgc acgctgaact cgaggctccg ggcgtgtggc ggccagtgtt     60 

acaaccaatt aacc                                                       74 

 
           
             19  
             83  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            19 

gattttccgg gaataccgga tattacgaat tactggtagt gacgtagata ataaaattat     60 

acgatttatt caacaaagcc acg                                             83 

 
           
             20  
             76  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            20 

caccaaagcc gttagcgtgc ccagagctac cgcacggtaa aatagggaca tgagccagtg     60 

ttacaaccaa ttaacc                                                     76 

 
           
             21  
             408  
             DNA  
             Human cytomegalovirus  
           
            21 

gtctgcaaca tgcggctgtc tcgggtgtgg ctgtctgttt gtctgtgcgc cgtggtgctg     60 

ggtcagtgcc agcgggagac cgcagaaaaa aacgattatt accgagtacc gcattactgg    120 

gacgcgtgct ctcgcgcgct gcctgaccaa acccgttaca agtatgtgga acagctcgtg    180 

gacctcacgt tgaactacca ctacgatgcg agccacggct tggacaactt tgacgtgctc    240 

aagagaatca acgtgaccga ggtgtcgttg ctcatcagcg actttatacg tcagaaccgt    300 

cgcggcggca ccaacaaaag gaccacgttc aacgccgccg gttcgctggc gcctcacgcc    360 

cggagcctcg agttcagcgt gcggctcttt gccaactagc ctgcgtca                 408 

 
           
             22  
             516  
             DNA  
             Human cytomegalovirus  
           
            22 

gtctgcaaca tgcggctgtg tcgggtgtgg ctgtctgttt gtctgtgcgc cgtggtgctg     60 

ggtcagtgcc agcgggagac cgcagaaaaa aacgattatt accgagtacc gcattactgg    120 

gacgcgtgct ctcgcgcgct gcctgaccaa acccgttaca agtatgtgga acagctcgtg    180 

gacctcacgt tgaactacca ctacgatgcg agccacggct tggacaactt tgacgtgctc    240 

aagaggtgag ggtacgcgct aaaggtgtat gacaacggga aggtaagggc gaacgggtaa    300 

cgggtaggta accgcatggg gtgtgaaatg acgttcggaa cctgtgcttg cagaatcaac    360 

gtgaccgagg tgtcgttgct catcagcgac tttagacgtc agaaccgtcg cggcggcacc    420 

aacaaaagga ccacgttcaa cgccgccggt tcgctggcgc ctcacgcccg gagcctcgag    480 

ttcagcgtgc ggctctttgc caactagcct gcgtca                              516 

 
           
             23  
             410  
             DNA  
             Human cytomegalovirus  
           
            23 

gtctgcaaca tgcggctgtg tcgggtgtgg ctgtctgttt gtctgtgcgc cgtggtgctg     60 

ggtcagtgcc agcgggagac cgcagaaaaa aaaacgatta ttaccgagta ccgcattact    120 

gggacgcgtg ctctcgcgcg ctgcctgacc aaacccgtta caagtatgtg gaacagctcg    180 

tggacctcac gttgaactac cactacgatg cgagccacgg cttggacaac tttgacgtgc    240 

tcaagagaat caacgtgacc gaggtgtcgt tgctcatcag cgactttaga cgtcagaacc    300 

gtcgcggcgg caccaacaaa aggaccacgt tcaacgccgc cggttcgctg gcgcctcacg    360 

cccggagcct cgagttcagc gtgcggctct ttgccaacta gcctgcgtca               410 

 
           
             24  
             516  
             DNA  
             Human cytomegalovirus  
           
            24 

gtctgcaaca tgcggctgtg tcgggtgtgg ctgtctgttt gtctgtgcgc cgtggtgctg     60 

ggtcagtgcc agcgggagac cgcagaaaaa aacgattatt accgagtacc gcattactgg    120 

gacgcgtgct ctcgcgcgct gcctgaccaa acccgttaca agtatgtgga acagctcgtg    180 

gacctcacgt tgaactacca ctacgatgcg agccacggct tggacaactt tgacgtgctc    240 

aagaggtgag ggtacgcgct aaaggtgtat gacaacggga aggtaagggc gaacgggtaa    300 

cgggtaggta accgcatggg gtgtgaaatg acgttcggaa cctgtgcttg cagaatcaac    360 

gtgaccgagg tgtcgttgct catcagcgac tttagacgtc agaaccgtcg cggcggcacc    420 

aacaaaagga ccacgttcaa cgccgccggt tcgctggcgc ctcacgcccg gagcctcgag    480 

ttcagcgtgc ggctctttgc caactagcct gcgtca                              516 

 
           
             25  
             656  
             DNA  
             Human cytomegalovirus  
           
            25 

ccgtgcgtca tgagtcccaa aaacctgacg ccgttcttga cggcgttgtg gctgctattg     60 

ggtcacagcc gcgtgccgcg ggtacgcgca gaagaatgtt gcgaattcat aaacgtcaac    120 

cacccgccgg aacgctgtta cgatttcaaa atgtgcaatc gcttcaccgt cgcgtacgta    180 

ttttcatgat tgtctgcgtt ctgtggtgcg tctggatctg tctctcgacg tttctgatag    240 

ccatgttcca tcgacgatcc tcgggaatgc cagagtagat tttcatgaat ccacaggctg    300 

cggtgtccgg acggcgaagt ctgctacagt cccgagaaaa cggctgagat tcgcgggatc    360 

gtcaccacca tgacccattc attgacacgc caggtcgtac acaacaaact gacgaactgc    420 

aactacaatc cgttatacct cgaagctgac gggcgaatac gctgcggcaa agtgaacgac    480 

aaggcgcagt acctgctggg cgccgctggc agcgttccct atcgatggat caacctggaa    540 

tacgacaaga taacccggat cgtgggcctg gatcagtacc tggagagcgt taagaaacac    600 

aaacggctgg atgtgtgccg cgctaaaatg ggctatatgc tgcagtgaat aataaa        656 

 
           
             26  
             656  
             DNA  
             Human cytomegalovirus  
           
            26 

ccgcgcgtca tgagtcccaa aaacctgacg ccgttcttga cggcgttgtg gctgctattg     60 

ggtcacagcc gcgtgccgcg ggtacgcgca gaagaatgtt gcgaattcat aaacgtcaac    120 

cacccgccgg aacgctgtta cgatttcaaa atgtgcaatc gcttcaccgt cgcgtacgta    180 

ttttcatgat tgtctgcgtt ctgtggtgcg tctggatctg tctctcgacg tttctgatag    240 

ccatgttcca tcgacgatcc tcgggaatgc cagagtagat tttcatgaat ccacaggctg    300 

cggtgtccgg acggcgaagt ctgctacagt cccgagaaaa cggctgagat tcgcgggatc    360 

gtcaccacca tgacccattc attgacacgc caggtcgtac acaacaaact gacgagctgc    420 

aactacaatc cgttatacct cgaagctgac gggcgaatac gctgcggcaa agtgaacgac    480 

aaggcgcagt acctgctggg cgccgctggc ggcgttccct atcgatggat caacctggaa    540 

tacgacaaga tagcccggat cgtgggcctg gatcagtacc tggagagcgt taagaaacac    600 

aaacggctgg atgtgtgccg cgctaaaatg ggctatatgc tgcagtgaat aataaa        656 

 
           
             27  
             533  
             DNA  
             Human cytomegalovirus  
           
            27 

ccgcgcgtca tgagtcccaa aaacctgacg ccgttcttga cggcgttgtg gctgctattg     60 

ggtcacagcc gcgtgccgcg ggtacgcgca gaagaatgtt gcgaattcat aaacgtcaac    120 

cacccgccgg aacgctgtta cgatttcaaa atgtgcaatc gcttcaccgt cgcgctgcgg    180 

tgtccggacg gcgaagtctg ctacagtccc gagaaaacgg ctgagattcg cgggatcgtc    240 

accaccatga cccattcatt gacacgccag gtcgtacaca acaaactgac gagctgcaac    300 

tacaatctgt tatacctcga agctgacggg cgaatacgct gcggcaaagt gaacgacaag    360 

gcgcagtacc tgctgggcgc cgctggcagc gttccctatc gatggatcaa cctggaatac    420 

gacaagataa cccggatcgt gggcctggat cagtacctgg agagcgttaa gaaatacaaa    480 

cggctggatg tgtgccgcgc taaaatgggc tatatgctgc agtgaataat aaa           533 

 
           
             28  
             775  
             DNA  
             Human cytomegalovirus  
           
            28 

ccgcgcgtca tgagtcccaa aaacctgacg ccgttcttga cggcgttgtg gctgctattg     60 

ggtcacagcc gcgtgccgcg ggtacgcgca gaagaatgtt gcgaattcat aaacgtcaac    120 

cacccgccgg aacgctgtta cgatttcaaa atgtgcaatc gcttcaccgt cgcgtacgta    180 

tttttatgat tgtctgcgtt ctgtggtgcg tctggatttg tctctcgacg tttctgatag    240 

ccatgttcca tcgacgatcc tcgggaatgc cagagtagat tttcatgaat ccacaggctg    300 

cggtgtccgg acggcgaagt ctgctacagt cccgagaaaa cggctgagat tcgcgggatc    360 

gtcaccacca tgacccattc attgacacgc caggtcgtac acaacaaact gacgagctgc    420 

aactacaatc cgtaagtctc ttcctcgagg gccttacagc ctatgggaaa gtaagacaga    480 

gggacaaaac atcattaaaa aaaaagtcta atttcacgtt ttgtaccccc ccttcccctc    540 

cgtgttgtag gttatacctc gaagctgacg ggcgaatacg ctgcggcaaa gtgaacgaca    600 

aggcgcagta cctgctgggc gccgctggca gcgttcccta tcgatggatc aacctggaat    660 

acgacaagat aacccggatc gtgggcctgg atcagtacct ggagagcgtt aagaaacaca    720 

aacggctgga tgtgtgccgc gctaaaatgg gctatatgct gcagtgaata ataaa         775 

 
           
             29  
             60  
             DNA  
             Human cytomegalovirus  
           
            29 

cgctaaaatg ggctatatgc tgcagtgaat aataaaatgt gtgtttgtcc gcaaaaaaaa     60 

 
           
             30  
             60  
             DNA  
             Human cytomegalovirus  
           
            30 

cgctaaaatg ggctatatgc tgcagtgaat aataaaatgt gtgtttgtcc aaaaaaaaaa     60 

 
           
             31  
             60  
             DNA  
             Human cytomegalovirus  
           
            31 

cgctaaaatg ggctatatgc tgcagtgaat aataaaatgt gtgtttgtcc aaaaaaaaaa     60 

 
           
             32  
             52  
             DNA  
             Human cytomegalovirus  
           
            32 

cgctaaaatg ggctatatgc tgcagtgaat aataaaatgt gtgtttgtcc ga             52 

 
           
             33  
             1977  
             DNA  
             Human cytomegalovirus  
           
            33 

gtctgcaaca tgcggctgtg tcgggtgtgg ctgtctgttt gtctgtgcgc cgtggtgctg     60 

ggtcagtgcc agcgggagac cgcagaaaaa aacgattatt accgagtacc gcattactgg    120 

gacgcgtgct ctcgcgcgct gcctgaccaa acccgttaca agtatgtgga acagctcgtg    180 

gacctcacgt tgaactacca ctacgatgcg agccacggct tggacaactt tgacgtgctc    240 

aagaggtgag ggtacgcgct aaaggtgtat gacaacggga aggtaagggc gaacgggtaa    300 

cgggtaggta accgcatggg gtgtgaaatg acgttcggaa cctgtgcttg cagaatcaac    360 

gtgaccgagg tgtcgttgct catcagcgac tttagacgtc agaaccgtcg cggcggcacc    420 

aacaaaagga ccacgttcaa cgccgccggt tcgctggcgc ctcacgcccg gagcctcgag    480 

ttcagcgtgc ggctctttgc caactagcct gcgtcacggg aaataatatg ctacggcttc    540 

tgcttcgtca ccactttcac tgcctgcttc tgtgcgcggt ttgggcaacg ccctgtctgg    600 

cgtctccgtg gttcacgcta acggcgaacc agaatccgtc cccgccatgg tctaaactga    660 

cgtatcccaa accgcatgac gcggcgacgt tttactgtcc ttttctctat ccctcgcccc    720 

cacggtcccc ctcgcaattc ccggggttcc agcgggtatc aacgggtccc gagtgtcgca    780 

acgagaccct gtatctgctg tacaaccggg aaggccagac cttggtggag agaagctcca    840 

cctgggtgaa aaaggtgatc tggtatctga gcggtcgcaa tcagaccatc ctccaacgga    900 

tgccccgaac ggcttcgaaa ccgagcgacg gaaacgtgca gatcagcgtg gaagacgcca    960 

agatttttgg agcgcacatg gtgcccaagc agaccaagct gctacgtttc gtcgtcaacg   1020 

atggcacacg ttatcagatg tgtgtgatga aactggagag ctgggcccac gtcttccggg   1080 

actacagcgt gtcttttcag gtgcgattga cgttcaccga ggccaataac cagacttaca   1140 

ccttctgcac ccatcccaat ctcatcgttt gagcccgtcg cgcgcgcagg gaattttgaa   1200 

aaccgcgcgt catgagtccc aaaaacctga cgccgttctt gacggcgttg tggctgctat   1260 

tgggtcacag ccgcgtgccg cgggtacgcg cagaagaatg ttgcgaattc ataaacgtca   1320 

accacccgcc ggaacgctgt tacgatttca aaatgtgcaa tcgcttcacc gtcgcgtacg   1380 

tattttcatg attgtctgcg ttctgtggtg cgtctggatt tgtctctcga cgtttctgat   1440 

agccatgttc catcgacgat cctcgggaat gccagagtag attttcatga atccacaggc   1500 

tgcggtgtcc ggacggcgaa gtctgctaca gtcccgagaa aacggctgag attcgcggga   1560 

tcgtcaccac catgacccat tcattgacac gccaggtcgt acacaacaaa ctgacgagct   1620 

gcaactacaa tccgtaagtc tcttcctcga gggccttaca gcctatggga aagtaagaca   1680 

gagggacaaa acatcattaa aaaaaaagtc taatttcacg ttttgtaccc ccccttcccc   1740 

tccgtgttgt aggttatacc tcgaagctga cgggcgaata cgctgcggca aagtgaacga   1800 

caaggcgcag tacctgctgg gcgccgctgg cagcgttccc tatcgatgga tcaacctgga   1860 

atacgacaag ataacccgga tcgtgggcct ggatcagtac ctggagagcg ttaagaaaca   1920 

caaacggctg gatgtgtgcc gcgctaaaat gggctatatg ctgcagtgaa taataaa      1977 

 
           
             34  
             129  
             PRT  
             Human cytomegalovirus  
           
            34 

Met Arg Leu Cys Arg Val Trp Leu Ser Val Cys Leu Cys Ala Val Val 
1               5                   10                  15 

Leu Gly Gln Cys Gln Arg Glu Thr Ala Glu Lys Asn Asp Tyr Tyr Arg 
            20                  25                  30 

Val Pro His Tyr Trp Asp Ala Cys Ser Arg Ala Leu Pro Asp Gln Thr 
        35                  40                  45 

Arg Tyr Lys Tyr Val Glu Gln Leu Val Asp Leu Thr Leu Asn Tyr His 
    50                  55                  60 

Tyr Asp Ala Ser His Gly Leu Asp Asn Phe Asp Val Leu Lys Arg Ile 
65                  70                  75                  80 

Asn Val Thr Glu Val Ser Leu Leu Ile Ser Asp Phe Arg Arg Gln Asn 
                85                  90                  95 

Arg Arg Gly Gly Thr Asn Lys Arg Thr Thr Phe Asn Ala Ala Gly Ser 
            100                 105                 110 

Leu Ala Pro His Ala Arg Ser Leu Glu Phe Ser Val Arg Leu Phe Ala 
        115                 120                 125 

Asn 

 
           
             35  
             30  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            35 

cggcacacat ccagccgttt gtgtttctta                                      30 

 
           
             36  
             30  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            36 

taacgctctc caggtactga tccaggccca                                      30 

 
           
             37  
             30  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            37 

tcgtcagttt gttgtgtacg acctggcgtg                                      30 

 
           
             38  
             30  
             DNA  
             Artificial Sequence  
             
               oligonucloetide primer  
             
           
            38 

tattggcctc ggtgaacgtc aatcgcacct                                      30 

 
           
             39  
             30  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            39 

tgtgtcgggt gtggctgtct gtttgtctgt                                      30 

 
           
             40  
             30  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            40 

tctgcttcgt caccactttc actgcctgct                                      30 

 
           
             41  
             30  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            41 

cgcagaagaa tgttgcgaat tcataaacgt                                      30 

 
           
             42  
             30  
             DNA  
             Artificial Sequence  
             
               oligonulceotide primer  
             
           
            42 

gctgcggtgt ccggacggcg aagtctgcta                                      30 

 
           
             43  
             30  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            43 

ccagctggca gattcccaaa ctaatgaaag                                      30 

 
           
             44  
             30  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            44 

ctttcggttc caactctttc cccgccccat                                      30 

 
           
             45  
             30  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            45 

cacctcgcct atactatgtg tatgatgtct                                      30 

 
           
             46  
             30  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            46 

ctctctttct cagtctgcaa catgcggctg                                      30 

 
           
             47  
             30  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            47 

gttgtccaag ccgtcgctcg catcgtagtg                                      30 

 
           
             48  
             30  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            48 

cataataaag ctctctttct cagtctgcaa                                      30 

 
           
             49  
             30  
             DNA  
             Artificial Sequence  
             
               oligonucleotide primer  
             
           
            49 

tatgatgtct cataataaag ctctctttct                                      30 

 
           
             50  
             390  
             DNA  
             Human cytomegalovirus  
           
            50 

atgcggctgt ctcgggtgtg gctgtctgtt tgtctgtgcg ccgtggtgct gggtcagtgc     60 

cagcgggaga ccgcagaaaa aaacgattat taccgagtac cgcattactg ggacgcgtgc    120 

tctcgcgcgc tgcctgacca aacccgttac aagtatgtgg aacagctcgt ggacctcacg    180 

ttgaactacc actacgatgc gagccacggc ttggacaact ttgacgtgct caagagaatc    240 

aacgtgaccg aggtgtcgtt gctcatcagc gactttatac gtcagaaccg tcgcggcggc    300 

accaacaaaa ggaccacgtt caacgccgcc ggttcgctgg cgcctcacgc ccggagcctc    360 

gagttcagcg tgcggctctt tgccaactag                                     390 

 
           
             51  
             129  
             PRT  
             Human cytomegalovirus  
           
            51 

Met Arg Leu Ser Arg Val Trp Leu Ser Val Cys Leu Cys Ala Val Val 
1               5                   10                  15 

Leu Gly Gln Cys Gln Arg Glu Thr Ala Glu Lys Asn Asp Tyr Tyr Arg 
            20                  25                  30 

Val Pro His Tyr Trp Asp Ala Cys Ser Arg Ala Leu Pro Asp Gln Thr 
        35                  40                  45 

Arg Tyr Lys Tyr Val Glu Gln Leu Val Asp Leu Thr Leu Asn Tyr His 
    50                  55                  60 

Tyr Asp Ala Ser His Gly Leu Asp Asn Phe Asp Val Leu Lys Arg Ile 
65                  70                  75                  80 

Asn Val Thr Glu Val Ser Leu Leu Ile Ser Asp Phe Ile Arg Gln Asn 
                85                  90                  95 

Arg Arg Gly Gly Thr Asn Lys Arg Thr Thr Phe Asn Ala Ala Gly Ser 
            100                 105                 110 

Leu Ala Pro His Ala Arg Ser Leu Glu Phe Ser Val Arg Leu Phe Ala 
        115                 120                 125 

Asn 

 
           
             52  
             240  
             DNA  
             Human cytomegalovirus  
           
            52 

atgcggctgt gtcgggtgtg gctgtctgtt tgtctgtgcg ccgtggtgct gggtcagtgc     60 

cagcgggaga ccgcagaaaa aaacgattat taccgagtac cgcattactg ggacgcgtgc    120 

tctcgcgcgc tgcctgacca aacccgttac aagtatgtgg aacagctcgt ggacctcacg    180 

ttgaactacc actacgatgc gagccacggc ttggacaact ttgacgtgct caagaggtga    240 

 
           
             53  
             79  
             PRT  
             Human cytomegalovirus  
           
            53 

Met Arg Leu Cys Arg Val Trp Leu Ser Val Cys Leu Cys Ala Val Val 
1               5                   10                  15 

Leu Gly Gln Cys Gln Arg Glu Thr Ala Glu Lys Asn Asp Tyr Tyr Arg 
            20                  25                  30 

Val Pro His Tyr Trp Asp Ala Cys Ser Arg Ala Leu Pro Asp Gln Thr 
        35                  40                  45 

Arg Tyr Lys Tyr Val Glu Gln Leu Val Asp Leu Thr Leu Asn Tyr His 
    50                  55                  60 

Tyr Asp Ala Ser His Gly Leu Asp Asn Phe Asp Val Leu Lys Arg 
65                  70                  75 

 
           
             54  
             1977  
             DNA  
             Human cytomegalovirus  
           
            54 

gtctgcaaca tgcggctgtg tcgggtgtgg ctgtctgttt gtctgtgcgc cgtggtgctg     60 

ggtcagtgcc agcgggagac cgcagaaaaa aacgattatt accgagtacc gcattactgg    120 

gacgcgtgct ctcgcgcgct gcctgaccaa acccgttaca agtatgtgga acagctcgtg    180 

gacctcacgt tgaactacca ctacgatgcg agccacggct tggacaactt tgacgtgctc    240 

aagaggtgag ggtacgcgct aaaggtgtat gacaacggga aggtaagggc gaacgggtaa    300 

cgggtaggta accgcatggg gtgtgaaatg acgttcggaa cctgtgcttg cagaatcaac    360 

gtgaccgagg tgtcgttgct catcagcgac tttagacgtc agaaccgtcg cggcggcacc    420 

aacaaaagga ccacgttcaa cgccgccggt tcgctggcgc ctcacgcccg gagcctcgag    480 

ttcagcgtgc ggctctttgc caactagcct gcgtcacggg aaataatatg ctacggcttc    540 

tgcttcgtca ccactttcac tgcctgcttc tgtgcgcggt ttgggcaacg ccctgtctgg    600 

cgtctccgtg gttcacgcta acggcgaacc agaatccgtc cccgccatgg tctaaactga    660 

cgtatcccaa accgcatgac gcggcgacgt tttactgtcc ttttctctat ccctcgcccc    720 

cacggtcccc ctcgcaattc ccggggttcc agcgggtatc aacgggtccc gagtgtcgca    780 

acgagaccct gtatctgctg tacaaccggg aaggccagac cttggtggag agaagctcca    840 

cctgggtgaa aaaggtgatc tggtatctga gcggtcgcaa tcagaccatc ctccaacgga    900 

tgccccgaac ggcttcgaaa ccgagcgacg gaaacgtgca gatcagcgtg gaagacgcca    960 

agatttttgg agcgcacatg gtgcccaagc agaccaagct gctacgtttc gtcgtcaacg   1020 

atggcacacg ttatcagatg tgtgtgatga aactggagag ctgggcccac gtcttccggg   1080 

actacagcgt gtcttttcag gtgcgattga cgttcaccga ggccaataac cagacttaca   1140 

ccttctgcac ccatcccaat ctcatcgttt gagcccgtcg cgcgcgcagg gaattttgaa   1200 

aaccgcgcgt catgagtccc aaaaacctga cgccgttctt gacggcgttg tggctgctat   1260 

tgggtcacag ccgcgtgccg cgggtacgcg cagaagaatg ttgcgaattc ataaacgtca   1320 

accacccgcc ggaacgctgt tacgatttca aaatgtgcaa tcgcttcacc gtcgcgtacg   1380 

tattttcatg attgtctgcg ttctgtggtg cgtctggatt tgtctctcga cgtttctgat   1440 

agccatgttc catcgacgat cctcgggaat gccagagtag attttcatga atccacaggc   1500 

tgcggtgtcc ggacggcgaa gtctgctaca gtcccgagaa aacggctgag attcgcggga   1560 

tcgtcaccac catgacccat tcattgacac gccaggtcgt acacaacaaa ctgacgagct   1620 

gcaactacaa tccgtaagtc tcttcctcga gggccttaca gcctatggga aagtaagaca   1680 

gagggacaaa acatcattaa aaaaaaagtc taatttcacg ttttgtaccc ccccttcccc   1740 

tccgtgttgt aggttatacc tcgaagctga cgggcgaata cgctgcggca aagtgaacga   1800 

caaggcgcag tacctgctgg gcgccgctgg cagcgttccc tatcgatgga tcaacctgga   1860 

atacgacaag ataacccgga tcgtgggcct ggatcagtac ctggagagcg ttaagaaaca   1920 

caaacggctg gatgtgtgcc gcgctaaaat gggctatatg ctgcagtgaa taataaa      1977 

 
           
             55  
             1741  
             DNA  
             Human cytomegalovirus  
           
            55 

atgcggctgt ctcgggtgtg gctgtctgtt tgtctgtgcg ccgtggtgct gggtcagtgc     60 

cagcgggaga ccgcagaaaa aaacgattat taccgagtac cgcattactg ggacgcgtgc    120 

tctcgcgcgc tgcctgacca aacccgttac aagtatgtgg aacagctcgt ggacctcacg    180 

ttgaactacc actacgatgc gagccacggc ttggacaact ttgacgtgct caagagaatc    240 

aacgtgaccg aggtgtcgtt gctcatcagc gactttatac gtcagaaccg tcgcggcggc    300 

accaacaaaa ggaccacgtt caacgccgcc ggttcgctgg cgcctcacgc ccggagcctc    360 

gagttcagcg tgcggctctt tgccaactag cctgcgtcac gggaaataat atgctacggc    420 

ttctgcttcg tcaccacttt cactgcctgc ttctgtgcgc ggtttgggca acgccctgtc    480 

tggcgtctcc gtggttcacg ctaacggcga accagaatcc gtccccgcca tggtctaaac    540 

tgacgtatcc caaaccgcat gacgcggcga cgttttactg tccttttctc tatccctcgc    600 

ccccacggtc cccctcgcaa ttcccggggt tccagcgggt atcaacgggt cccgagtgtc    660 

gcaacgagac cctgtatctg ctgtacaacc gggaaggcca gaccttggtg gagagaagct    720 

ccacctgggt gaaaaaggtg atctggtatc tgagcggtcg caatcagacc atcctccaac    780 

ggatgccccg aacggcttcg aaaccgagcg acggaaacgt gcagatcagc gtggaagacg    840 

ccaagatttt tggagcgcac atggtgccca agcagaccaa gctgctacgt ttcgtcgcca    900 

acgatggcac acgttatcag atgtgtgtga tgaaactgga gagctgggcc cacgtcttcc    960 

gggactacag cgtgtctttt caggtgcgat tgacgttcac cgaggccaat aaccagactt   1020 

acaccttctg cacccatccc aatctcatcg tttgagcccg tcgcgcgcgc agggaatttt   1080 

gaaaaccgtg cgtcatgagt cccaaaaacc tgacgccgtt cttgacggcg ttgtggctgc   1140 

tattgggtca cagccgcgtg ccgcgggtac gcgcagaaga atgttgcgaa ttcataaacg   1200 

tcaaccaccc gccggaacgc tgttacgatt tcaaaatgtg caatcgcttc accgtcgcgt   1260 

acgtattttc atgattgtct gcgttctgtg gtgcgtctgg atctgtctct cgacgtttct   1320 

gatagccatg ttccatcgac gatcctcggg aatgccagag tagattttca tgaatccaca   1380 

ggctgcggtg tccggacggc gaagtctgct acagtcccga gaaaacggct gagattcgcg   1440 

ggatcgtcac caccatgacc cattcattga cacgccaggt cgtacacaac aaactgacga   1500 

actgcaacta caatccgtta tacctcgaag ctgacgggcg aatacgctgc ggcaaagtga   1560 

acgacaaggc gcagtacctg ctgggcgccg ctggcagcgt tccctatcga tggatcaacc   1620 

tggaatacga caagataacc cggatcgtgg gcctggatca gtacctggag agcgttaaga   1680 

aacacaaacg gctggatgtg tgccgcgcta aaatgggcta tatgctgcag tgaataataa   1740 

a                                                                   1741 

 
           
             56  
             390  
             DNA  
             Human cytomegalovirus  
           
            56 

atgcggctgt ctcgggtgtg gctgtctgtt tgtctgtgcg ccgtggtgct gggtcagtgc     60 

cagcgggaga ccgcagaaaa aaacgattat taccgagtac cgcattactg ggacgcgtgc    120 

tctcgcgcgc tgcctgacca aacccgttac aagtatgtgg aacagctcgt ggacctcacg    180 

ttgaactacc actacgatgc gagccacggc ttggacaact ttgacgtgct caagagaatc    240 

aacgtgaccg aggtgtcgtt gctcatcagc gactttatac gtcagaaccg tcgcggcggc    300 

accaacaaaa ggaccacgtt caacgccgcc ggttcgctgg cgcctcacgc ccggagcctc    360 

gagttcagcg tgcggctctt tgccaactag                                     390 

 
           
             57  
             129  
             PRT  
             Human cytomegalovirus  
           
            57 

Met Arg Leu Ser Arg Val Trp Leu Ser Val Cys Leu Cys Ala Val Val 
1               5                   10                  15 

Leu Gly Gln Cys Gln Arg Glu Thr Ala Glu Lys Asn Asp Tyr Tyr Arg 
            20                  25                  30 

Val Pro His Tyr Trp Asp Ala Cys Ser Arg Ala Leu Pro Asp Gln Thr 
        35                  40                  45 

Arg Tyr Lys Tyr Val Glu Gln Leu Val Asp Leu Thr Leu Asn Tyr His 
    50                  55                  60 

Tyr Asp Ala Ser His Gly Leu Asp Asn Phe Asp Val Leu Lys Arg Ile 
65                  70                  75                  80 

Asn Val Thr Glu Val Ser Leu Leu Ile Ser Asp Phe Ile Arg Gln Asn 
                85                  90                  95 

Arg Arg Gly Gly Thr Asn Lys Arg Thr Thr Phe Asn Ala Ala Gly Ser 
            100                 105                 110 

Leu Ala Pro His Ala Arg Ser Leu Glu Phe Ser Val Arg Leu Phe Ala 
        115                 120                 125 

Asn 

 
           
             58  
             1977  
             DNA  
             Human cytomegalovirus  
           
            58 

gtctgcaaca tgcggctgtg tcgggtgtgg ctgtctgttt gtctgtgcgc cgtggtgctg     60 

ggtcagtgcc agcgggagac cgcagaaaaa aacgattatt accgagtacc gcattactgg    120 

gacgcgtgct ctcgcgcgct gcctgaccaa acccgttaca agtatgtgga acagctcgtg    180 

gacctcacgt tgaactacca ctacgatgcg agccacggct tggacaactt tgacgtgctc    240 

aagaggtgag ggtacgcgct aaaggtgtat gacaacggga aggtaagggc gaacgggtaa    300 

cgggtaggta accgcatggg gtgtgaaatg acgttcggaa cctgtgcttg cagaatcaac    360 

gtgaccgagg tgtcgttgct catcagcgac tttagacgtc agaaccgtcg cggcggcacc    420 

aacaaaagga ccacgttcaa cgccgccggt tcgctggcgc ctcacgcccg gagcctcgag    480 

ttcagcgtgc ggctctttgc caactagcct gcgtcacggg aaataatatg ctacggcttc    540 

tgcttcgtca ccactttcac tgcctgcttc tgtgcgcggt ttgggcaacg ccctgtctgg    600 

cgtctccgtg gttcacgcta acggcgaacc agaatccgtc cccgccatgg tctaaactga    660 

cgtatcccaa accgcatgac gcggcgacgt tttactgtcc ttttctctat ccctcgcccc    720 

cacggtcccc ctcgcaattc ccggggttcc agcgggtatc aacgggtccc gagtgtcgca    780 

acgagaccct gtatctgctg tacaaccggg aaggccagac cttggtggag agaagctcca    840 

cctgggtgaa aaaggtgatc tggtatctga gcggtcgcaa tcagaccatc ctccaacgga    900 

tgccccgaac ggcttcgaaa ccgagcgacg gaaacgtgca gatcagcgtg gaagacgcca    960 

agatttttgg agcgcacatg gtgcccaagc agaccaagct gctacgtttc gtcgtcaacg   1020 

atggcacacg ttatcagatg tgtgtgatga aactggagag ctgggcccac gtcttccggg   1080 

actacagcgt gtcttttcag gtgcgattga cgttcaccga ggccaataac cagacttaca   1140 

ccttctgcac ccatcccaat ctcatcgttt gagcccgtcg cgcgcgcagg gaattttgaa   1200 

aaccgcgcgt catgagtccc aaaaacctga cgccgttctt gacggcgttg tggctgctat   1260 

tgggtcacag ccgcgtgccg cgggtacgcg cagaagaatg ttgcgaattc ataaacgtca   1320 

accacccgcc ggaacgctgt tacgatttca aaatgtgcaa tcgcttcacc gtcgcgtacg   1380 

tattttcatg attgtctgcg ttctgtggtg cgtctggatt tgtctctcga cgtttctgat   1440 

agccatgttc catcgacgat cctcgggaat gccagagtag attttcatga atccacaggc   1500 

tgcggtgtcc ggacggcgaa gtctgctaca gtcccgagaa aacggctgag attcgcggga   1560 

tcgtcaccac catgacccat tcattgacac gccaggtcgt acacaacaaa ctgacgagct   1620 

gcaactacaa tccgtaagtc tcttcctcga gggccttaca gcctatggga aagtaagaca   1680 

gagggacaaa acatcattaa aaaaaaagtc taatttcacg ttttgtaccc ccccttcccc   1740 

tccgtgttgt aggttatacc tcgaagctga cgggcgaata cgctgcggca aagtgaacga   1800 

caaggcgcag tacctgctgg gcgccgctgg cagcgttccc tatcgatgga tcaacctgga   1860 

atacgacaag ataacccgga tcgtgggcct ggatcagtac ctggagagcg ttaagaaaca   1920 

caaacggctg gatgtgtgcc gcgctaaaat gggctatatg ctgcagtgaa taataaa      1977 

 
           
             59  
             1849  
             DNA  
             Human cytomegalovirus  
           
            59 

atgcggctgt gtcgggtgtg gctgtctgtt tgtctgtgcg ccgtggtgct gggtcagtgc     60 

cagcgggaga ccgcagaaaa aaacgattat taccgagtac cgcattactg ggacgcgtgc    120 

tctcgcgcgc tgcctgacca aacccgttac aagtatgtgg aacagctcgt ggacctcacg    180 

ttgaactacc actacgatgc gagccacggc ttggacaact ttgacgtgct caagaggtga    240 

gggtacgcgc taaaggtgta tgacaacggg aaggtaaggg cgaacgggta acgggtaggt    300 

aaccgcatgg ggtgtgaaat gacgttcgga acctgtgctt gcagaatcaa cgtgaccgag    360 

gtgtcgttgc tcatcagcga ctttagacgt cagaaccgtc gcggcggcac caacaaaagg    420 

accacgttca acgccgccgg ttcgctggcg cctcacgccc ggagcctcga gttcagcgtg    480 

cggctctttg ccaactagcc tgcgtcacgg gaaataatat gctacggctt ctgcttcgtc    540 

accactttca ctgcctgctt ctgtgcgcgg tttgggcaac gccctgtctg gcgtctccgt    600 

ggttcacgct aacggcgaac cagaatccgt ccccgccatg gtctaaactg acgtatccca    660 

aaccgcatga cgcggcgacg ttttactgtc cttttctcta tccctcgccc ccacggtccc    720 

cctcgcaatt cccggggttc cagcgggtat caacgggtcc cgagtgtcgc aacgagaccc    780 

tgtatctgct gtacaaccgg gaaggccaga ccttggtgga gagaagctcc acctgggtga    840 

aaaaggtgat ctggtatctg agcggtcgca atcagaccat cctccaacgg atgccccgaa    900 

cggcttcgaa accgagcgac ggaaacgtgc agatcagcgt ggaagacgcc aagatttttg    960 

gagcgcacat ggtgcccaag cagaccaagc tgctacgttt cgtcgtcaac gatggcacac   1020 

gttatcagat gtgtgtgatg aaactggaga gctgggccca cgtcttccgg gactacagcg   1080 

tgtcttttca ggtgcgattg acgttcaccg aggccgataa ccagacttac accttctgca   1140 

cccatcccaa tctcatcgtt tgagcccgtc gcgcgcgcag ggaattttga aaaccgcgcg   1200 

tcatgagtcc caaaaacctg acgccgttct tgacggcgtt gtggctgcta ttgggtcaca   1260 

gccgcgtgcc gcgggtacgc gcagaagaat gttgcgaatt cataaacgtc aaccacccgc   1320 

cggaacgctg ttacgatttc aaaatgtgca atcgcttcac cgtcgcgtac gtattttcat   1380 

gattgtctgc gttctgtggt gcgtctggat ctgtctctcg acgtttctga tagccatgtt   1440 

ccatcgacga tcctcgggaa tgccagagta gattttcatg aatccacagg ctgcggtgtc   1500 

cggacggcga agtctgctac agtcccgaga aaacggctga gattcgcggg atcgtcacca   1560 

ccatgaccca ttcattgaca cgccaggtcg tacacaacaa actgacgagc tgcaactaca   1620 

atccgttata cctcgaagct gacgggcgaa tacgctgcgg caaagtgaac gacaaggcgc   1680 

agtacctgct gggcgccgct ggcggcgttc cctatcgatg gatcaacctg gaatacgaca   1740 

agatagcccg gatcgtgggc ctggatcagt acctggagag cgttaagaaa cacaaacggc   1800 

tggatgtgtg ccgcgctaaa atgggctata tgctgcagtg aataataaa               1849 

 
           
             60  
             240  
             DNA  
             Human cytomegalovirus  
           
            60 

atgcggctgt gtcgggtgtg gctgtctgtt tgtctgtgcg ccgtggtgct gggtcagtgc     60 

cagcgggaga ccgcagaaaa aaacgattat taccgagtac cgcattactg ggacgcgtgc    120 

tctcgcgcgc tgcctgacca aacccgttac aagtatgtgg aacagctcgt ggacctcacg    180 

ttgaactacc actacgatgc gagccacggc ttggacaact ttgacgtgct caagaggtga    240 

 
           
             61  
             79  
             PRT  
             Human cytomegalovirus  
           
            61 

Met Arg Leu Cys Arg Val Trp Leu Ser Val Cys Leu Cys Ala Val Val 
1               5                   10                  15 

Leu Gly Gln Cys Gln Arg Glu Thr Ala Glu Lys Asn Asp Tyr Tyr Arg 
            20                  25                  30 

Val Pro His Tyr Trp Asp Ala Cys Ser Arg Ala Leu Pro Asp Gln Thr 
        35                  40                  45 

Arg Tyr Lys Tyr Val Glu Gln Leu Val Asp Leu Thr Leu Asn Tyr His 
    50                  55                  60 

Tyr Asp Ala Ser His Gly Leu Asp Asn Phe Asp Val Leu Lys Arg 
65                  70                  75 

 
           
             62  
             180  
             DNA  
             Human cytomegalovirus  
           
            62 

atgagtccca aaaacctgac gccgttcttg acggcgttgt ggctgctatt gggtcacagc     60 

cgcgtgccgc gggtacgcgc agaagaatgt tgcgaattca taaacgtcaa ccacccgccg    120 

gaacgctgtt acgatttcaa aatgtgcaat cgcttcaccg tcgcgtacgt attttcatga    180 

 
           
             63  
             59  
             PRT  
             Human cytomegalovirus  
           
            63 

Met Ser Pro Lys Asn Leu Thr Pro Phe Leu Thr Ala Leu Trp Leu Leu 
1               5                   10                  15 

Leu Gly His Ser Arg Val Pro Arg Val Arg Ala Glu Glu Cys Cys Glu 
            20                  25                  30 

Phe Ile Asn Val Asn His Pro Pro Glu Arg Cys Tyr Asp Phe Lys Met 
        35                  40                  45 

Cys Asn Arg Phe Thr Val Ala Tyr Val Phe Ser 
    50                  55 

 
           
             64  
             515  
             DNA  
             Human cytomegalovirus  
           
            64 

atgagtccca aaaacctgac gccgttcttg acggcgttgt ggctgctatt gggtcacagc     60 

cgcgtgccgc gggtacgcgc agaagaatgt tgcgaattca taaacgtcaa ccacccgccg    120 

gaacgctgtt acgatttcaa aatgtgcaat cgcttcaccg tcgcactgcg gtgtccggac    180 

ggcgaagtct gctacagtcc cgagaaacgg ctgagattcg cgggatcgtc accaccatga    240 

cccattcatt gacacgccag gtcgtacaca acaaactgac gagctgcaac tacaatctgt    300 

tatacctcga agctgacggg cgaatacgct gcggcaaagt gaacgacaag gcgcagtacc    360 

tgctgggcgc cgctggcagc gttccctatc gatggatcaa cctggaatac gacaagataa    420 

cccggatcgt gggcctggat cagtacctgg agagcgttaa gaaacacaaa cggctggatg    480 

tgtgccgcgc taaaatgggc tatatgctgc agtga                               515 

 
           
             65  
             171  
             PRT  
             Human cytomegalovirus  
           
            65 

Met Ser Pro Lys Asn Leu Thr Pro Phe Leu Thr Ala Leu Trp Leu Leu 
1               5                   10                  15 

Leu Gly His Ser Arg Val Pro Arg Val Arg Ala Glu Glu Cys Cys Glu 
            20                  25                  30 

Phe Ile Asn Val Asn His Pro Pro Glu Arg Cys Tyr Asp Phe Lys Met 
        35                  40                  45 

Cys Asn Arg Phe Thr Val Ala Leu Arg Cys Pro Asp Gly Glu Val Cys 
    50                  55                  60 

Tyr Ser Pro Glu Lys Thr Ala Glu Ile Arg Gly Ile Val Thr Thr Met 
65                  70                  75                  80 

Thr His Ser Leu Thr Arg Gln Val Val His Asn Lys Leu Thr Ser Cys 
                85                  90                  95 

Asn Tyr Asn Leu Leu Tyr Leu Glu Ala Asp Gly Arg Ile Arg Cys Gly 
            100                 105                 110 

Lys Val Asn Asp Lys Ala Gln Tyr Leu Leu Gly Ala Ala Gly Ser Val 
        115                 120                 125 

Pro Tyr Arg Trp Ile Asn Leu Glu Tyr Asp Lys Ile Thr Arg Ile Val 
    130                 135                 140 

Gly Leu Asp Gln Tyr Leu Glu Ser Val Lys Lys His Lys Arg Leu Asp 
145                 150                 155                 160 

Val Cys Arg Ala Lys Met Gly Tyr Met Leu Gln 
                165                 170 

 
           
             66  
             804  
             DNA  
             Human cytomegalovirus  
           
            66 

atgagtccca aaaacctgac gccgttcttg acggcgttgt ggctgctatt gggtcacagc     60 

cgcgtgccgc gggtacgcgc agaagaatgt tgcgaattca taaacgtcaa ccacccgccg    120 

gaacgctgtt acgatttcaa aatgtgcaat cgcttcaccg tcgcgtacgt attttcatga    180 

ttgtctgcgt tctgtggtgc gtctggatct gtctctcgac gtttctgata gccatgttcc    240 

atcgacgatc ctcgggaatg ccagagtaga ttttcatgaa tccacaggct gcggtgtccg    300 

gacggcgaag tctgctacag tcccgagaaa acggctgaga ttcgcgggat cgtcaccacc    360 

atgacccatt cattgacacg ccaggtcgta cacaacaaac tgacgagctg caactacaat    420 

ccgtaagtct cttcctcgag ggccttacag cctatgggaa agtaagacag agggacaaaa    480 

catcattaaa aaaaaagtct aatttcacgt tttgtacccc cccttcccct ccgtgttgta    540 

ggttatacct cgaagctgac gggcgaatac gctgcggcaa agtgaacgac aaggcgcagt    600 

acctgctggg cgccgctggc ggcgttccct atcgatggat caacctggaa tacgacaaga    660 

tagcccggat cgtgggcctg gatcagtacc tggagagcgt taagaaacac aaacggctgg    720 

atgtgtgccg cgctaaaatg ggctatatgc tgcagtgaat aataaaatgt gtgtttgtcc    780 

gaaatacgcg ttttgagatt tctg                                           804 

 
           
             67  
             685  
             DNA  
             Human cytomegalovirus  
           
            67 

atgagtccca aaaacctgac gccgttcttg acggcgttgt ggctgctatt gggtcacagc     60 

cgcgtgccgc gggtacgcgc agaagaatgt tgcgaattca taaacgtcaa ccacccgccg    120 

gaacgctgtt acgatttcaa aatgtgcaat cgcttcaccg tcgcgtacgt attttcatga    180 

ttgtctgcgt tctgtggtgc gtctggatct gtctctcgac gtttctgata gccatgttcc    240 

atcgacgatc ctcgggaatg ccagagtaga ttttcatgaa tccacaggct gcggtgtccg    300 

gacggcgaag tctgctacag tcccgagaaa acggctgaga ttcgcgggat cgtcaccacc    360 

atgacccatt cattgacacg ccaggtcgta cacaacaaac tgacgagctg caactacaat    420 

ccgttatacc tcgaagctga cgggcgaata cgctgcggca aagtgaacga caaggcgcag    480 

tacctgctgg gcgccgctgg cggcgttccc tatcgatgga tcaacctgga atacgacaag    540 

atagcccgga tcgtgggcct ggatcagtac ctggagagcg ttaagaaaca caaacggctg    600 

gatgtgtgcc gcgctaaaat gggctatatg ctgcagtgaa taataaaatg tgtgtttgtc    660 

caaaaaaaaa aaaaaaaaaa aaaaa                                          685 

 
           
             68  
             180  
             DNA  
             Human cytomegalovirus  
           
            68 

atgagtccca aaaacctgac gccgttcttg acggcgttgt ggctgctatt gggtcacagc     60 

cgcgtgccgc gggtacgcgc agaagaatgt tgcgaattca taaacgtcaa ccacccgccg    120 

gaacgctgtt acgatttcaa aatgtgcaat cgcttcaccg tcgcgtacgt attttcatga    180 

 
           
             69  
             59  
             PRT  
             Human cytomegalovirus  
           
            69 

Met Ser Pro Lys Asn Leu Thr Pro Phe Leu Thr Ala Leu Trp Leu Leu 
1               5                   10                  15 

Leu Gly His Ser Arg Val Pro Arg Val Arg Ala Glu Glu Cys Cys Glu 
            20                  25                  30 

Phe Ile Asn Val Asn His Pro Pro Glu Arg Cys Tyr Asp Phe Lys Met 
        35                  40                  45 

Cys Asn Arg Phe Thr Val Ala Tyr Val Phe Ser 
    50                  55 

 
           
             70  
             780  
             DNA  
             Human cytomegalovirus  
           
            70 

atgagtccca aaaacctgac gccgttcttg acggcgttgt ggctgctatt gggtcacagc     60 

cgcgtgccgc gggtacgcgc agaagaatgt tgcgaattca taaacgtcaa ccacccgccg    120 

gaacgctgtt acgatttcaa aatgtgcaat cgcttcaccg tcgcgtacgt atttttatga    180 

ttgtctgcgt tctgtggtgc gtctggattt gtctctcgac gtttctgata gccatgttcc    240 

atcgacgatc ctcgggaatg ccagagtaga ttttcatgaa tccacaggct gcggtgtccg    300 

gacggcgaag tctgctacag tcccgagaaa acggctgaga ttcgcgggat cgtcaccacc    360 

atgacccatt cattgacacg ccaggtcgta cacaacaaac tgacgagctg caactacaat    420 

ccgtaagtct cttcctcgag ggccttacag cctatgggaa agtaagacag agggacaaaa    480 

catcattaaa aaaaaagtct aatttcacgt tttgtacccc cccttcccct ccgtgttgta    540 

ggttatacct cgaagctgac gggcgaatac gctgcggcaa agtgaacgac aaggcgcagt    600 

acctgctggg cgccgctggc agcgttccct atcgatggat caacctggaa tacgacaaga    660 

taacccggat cgtgggcctg gatcagtacc tggagagcgt taagaaacac aaacggctgg    720 

atgtgtgccg cgctaaaatg ggctatatgc tgcagtgaat aataaaatgt gtgtttgtcc    780 

 
           
             71  
             529  
             DNA  
             Human cytomegalovirus  
           
            71 

atgagtccca aaaacctgac gccgttcttg acggcgttgt ggctgctatt gggtcacagc     60 

cgcgtgccgc gggtacgcgc agaagaatgt tgcgaattca taaacgtcaa ccacccgccg    120 

gaacgctgtt acgatttcaa aatgtgcaat cgcttcaccg tcgcgctgcg gtgtccggac    180 

ggcgaagtct gctacagtcc cgagaaaacg gctgagattc gcgggatcgt caccaccatg    240 

acccattcat tgacacgcca ggtcgtacac aacaaactga cgagctgcaa ctacaatccg    300 

ttatacctcg aagctgacgg gcgaatacgc tgcggcaaag tgaacgacaa ggcgcagtac    360 

ctgctgggcg ccgctggcag cgttccctat cgatggatca acctggaata cgacaagata    420 

acccggatcg tgggcctgga tcagtacctg gagagcgtta agaaacacaa acggctggat    480 

gtgtgccgcg ctaaaatggg ctatatgctg cagtgaataa taaaatgtg                529 

 
           
             72  
             515  
             DNA  
             Human cytomegalovirus  
           
            72 

atgagtccca aaaacctgac gccgttcttg acggcgttgt ggctgctatt gggtcacagc     60 

cgcgtgccgc gggtacgcgc agaagaatgt tgcgaattca taaacgtcaa ccacccgccg    120 

gaacgctgtt acgatttcaa aatgtgcaat cgcttcaccg tcgcactgcg gtgtccggac    180 

ggcgaagtct gctacagtcc cgagaaacgg ctgagattcg cgggatcgtc accaccatga    240 

cccattcatt gacacgccag gtcgtacaca acaaactgac gagctgcaac tacaatctgt    300 

tatacctcga agctgacggg cgaatacgct gcggcaaagt gaacgacaag gcgcagtacc    360 

tgctgggcgc cgctggcagc gttccctatc gatggatcaa cctggaatac gacaagataa    420 

cccggatcgt gggcctggat cagtacctgg agagcgttaa gaaacacaaa cggctggatg    480 

tgtgccgcgc taaaatgggc tatatgctgc agtga                               515 

 
           
             73  
             171  
             PRT  
             Human cytomegalovirus  
           
            73 

Met Ser Pro Lys Asn Leu Thr Pro Phe Leu Thr Ala Leu Trp Leu Leu 
1               5                   10                  15 

Leu Gly His Ser Arg Val Pro Arg Val Arg Ala Glu Glu Cys Cys Glu 
            20                  25                  30 

Phe Ile Asn Val Asn His Pro Pro Glu Arg Cys Tyr Asp Phe Lys Met 
        35                  40                  45 

Cys Asn Arg Phe Thr Val Ala Leu Arg Cys Pro Asp Gly Glu Val Cys 
    50                  55                  60 

Tyr Ser Pro Glu Lys Thr Ala Glu Ile Arg Gly Ile Val Thr Thr Met 
65                  70                  75                  80 

Thr His Ser Leu Thr Arg Gln Val Val His Asn Lys Leu Thr Ser Cys 
                85                  90                  95 

Asn Tyr Asn Leu Leu Tyr Leu Glu Ala Asp Gly Arg Ile Arg Cys Gly 
            100                 105                 110 

Lys Val Asn Asp Lys Ala Gln Tyr Leu Leu Gly Ala Ala Gly Ser Val 
        115                 120                 125 

Pro Tyr Arg Trp Ile Asn Leu Glu Tyr Asp Lys Ile Thr Arg Ile Val 
    130                 135                 140 

Gly Leu Asp Gln Tyr Leu Glu Ser Val Lys Lys His Lys Arg Leu Asp 
145                 150                 155                 160 

Val Cys Arg Ala Lys Met Gly Tyr Met Leu Gln 
                165                 170 

 
           
             74  
             1977  
             DNA  
             Human cytomegalovirus  
           
            74 

gtctgcaaca tgcggctgtg tcgggtgtgg ctgtctgttt gtctgtgcgc cgtggtgctg     60 

ggtcagtgcc agcgggagac cgcagaaaaa aacgattatt accgagtacc gcattactgg    120 

gacgcgtgct ctcgcgcgct gcctgaccaa acccgttaca agtatgtgga acagctcgtg    180 

gacctcacgt tgaactacca ctacgatgcg agccacggct tggacaactt tgacgtgctc    240 

aagaggtgag ggtacgcgct aaaggtgtat gacaacggga aggtaagggc gaacgggtaa    300 

cgggtaggta accgcatggg gtgtgaaatg acgttcggaa cctgtgcttg cagaatcaac    360 

gtgaccgagg tgtcgttgct catcagcgac tttagacgtc agaaccgtcg cggcggcacc    420 

aacaaaagga ccacgttcaa cgccgccggt tcgctggcgc ctcacgcccg gagcctcgag    480 

ttcagcgtgc ggctctttgc caactagcct gcgtcacggg aaataatatg ctacggcttc    540 

tgcttcgtca ccactttcac tgcctgcttc tgtgcgcggt ttgggcaacg ccctgtctgg    600 

cgtctccgtg gttcacgcta acggcgaacc agaatccgtc cccgccatgg tctaaactga    660 

cgtatcccaa accgcatgac gcggcgacgt tttactgtcc ttttctctat ccctcgcccc    720 

cacggtcccc ctcgcaattc ccggggttcc agcgggtatc aacgggtccc gagtgtcgca    780 

acgagaccct gtatctgctg tacaaccggg aaggccagac cttggtggag agaagctcca    840 

cctgggtgaa aaaggtgatc tggtatctga gcggtcgcaa tcagaccatc ctccaacgga    900 

tgccccgaac ggcttcgaaa ccgagcgacg gaaacgtgca gatcagcgtg gaagacgcca    960 

agatttttgg agcgcacatg gtgcccaagc agaccaagct gctacgtttc gtcgtcaacg   1020 

atggcacacg ttatcagatg tgtgtgatga aactggagag ctgggcccac gtcttccggg   1080 

actacagcgt gtcttttcag gtgcgattga cgttcaccga ggccaataac cagacttaca   1140 

ccttctgcac ccatcccaat ctcatcgttt gagcccgtcg cgcgcgcagg gaattttgaa   1200 

aaccgcgcgt catgagtccc aaaaacctga cgccgttctt gacggcgttg tggctgctat   1260 

tgggtcacag ccgcgtgccg cgggtacgcg cagaagaatg ttgcgaattc ataaacgtca   1320 

accacccgcc ggaacgctgt tacgatttca aaatgtgcaa tcgcttcacc gtcgcgtacg   1380 

tattttcatg attgtctgcg ttctgtggtg cgtctggatt tgtctctcga cgtttctgat   1440 

agccatgttc catcgacgat cctcgggaat gccagagtag attttcatga atccacaggc   1500 

tgcggtgtcc ggacggcgaa gtctgctaca gtcccgagaa aacggctgag attcgcggga   1560 

tcgtcaccac catgacccat tcattgacac gccaggtcgt acacaacaaa ctgacgagct   1620 

gcaactacaa tccgtaagtc tcttcctcga gggccttaca gcctatggga aagtaagaca   1680 

gagggacaaa acatcattaa aaaaaaagtc taatttcacg ttttgtaccc ccccttcccc   1740 

tccgtgttgt aggttatacc tcgaagctga cgggcgaata cgctgcggca aagtgaacga   1800 

caaggcgcag tacctgctgg gcgccgctgg cagcgttccc tatcgatgga tcaacctgga   1860 

atacgacaag ataacccgga tcgtgggcct ggatcagtac ctggagagcg ttaagaaaca   1920 

caaacggctg gatgtgtgcc gcgctaaaat gggctatatg ctgcagtgaa taataaa      1977 

 
           
             75  
             1620  
             DNA  
             Human cytomegalovirus  
           
            75 

atgcggctgt gtcgggtgtg gctgtctgtt tgtctgtgcg ccgtggtgct gggtcagtgc     60 

cagcgggaga ccgcagaaaa aaaaacgatt attaccgagt accgcattac tgggacgcgt    120 

gctctcgcgc gctgcctgac caaacccgtt acaagtatgt ggaacagctc gtggacctca    180 

cgttgaacta ccactacgat gcgagccacg gcttggacaa ctttgacgtg ctcaagagaa    240 

tcaacgtgac cgaggtgtcg ttgctcatca gcgactttag acgtcagaac cgtcgcggcg    300 

gcaccaacaa aaggaccacg ttcaacgccg ccggttcgct ggcgcctcac gcccggagcc    360 

tcgagttcag cgtgcggctc tttgccaact agcctgcgtc acgggaaata atatgctacg    420 

gcttctgctt cgtcaccact ttcactgcct gcttctgtgc gcggtttggg caacgccctg    480 

tctggcgtct ccgtggttca cgctaacggc gaaccagaat ccgtccccgc catggtctaa    540 

actgacgtat cccaaaccgc atgacgcggc gacgttttac tgtccttttc tctatccctc    600 

gcccccacgg tccccctcgc aattcccggg gttccagcgg gtattaacgg gtcccgagtg    660 

tcgcaacgag accctgtatc tgctgtacaa ccgggaaggc cagaccttgg tggagagaag    720 

ctccacctgg gtgaaaaagg tgatctggca tctgagcggt cgcaatcaga ccatcctcca    780 

acggatgccc cgaacggctt cgaaaccgag cgacggaaac gtgcagatca gcgtggaaga    840 

cgccaagatt tttggagcgc acatggtgcc caagcagacc aagctgctac gtttcgtcgc    900 

caacgatggc acacgttatt agatgtgtgt gatgaaactg gagagctggg cccacgtctt    960 

ccgggactac agcgtgtctt ttcaggtgcg attgacgttc accgaggcca ataaccagac   1020 

ttacaccttc tgcacccatc ccaatctcat cgtttgagcc cgtcgcgcgc gcagggaatt   1080 

ttgaaaaccg cgcgtcatga gtcccaaaaa cctgacgccg ttcttgacgg cgttgtggct   1140 

gctattgggt cacagccgcg tgccgcgggt acgcgcagaa gaatgttgcg aattcataaa   1200 

cgtcaaccac ccgccggaac gctgttacga tttcaaaatg tgcaatcgct tcaccgtcgc   1260 

actgcggtgt ccggacggcg aagtctgcta cagtcccgag aaaacggctg agattcgcgg   1320 

gatcgtcacc accatgaccc attcattgac acgccaggtc gtacacaaca aactgacgag   1380 

ctgcaactac aatctgttat acctcgaagc tgacgggcga atacgctgcg gcaaagtgaa   1440 

cgacaaggcg cagtacctgc tgggcgccgc tggcagcgtt ccctatcgat ggatcaacct   1500 

ggaatacgac aagataaccc ggatcgtggg cctggatcag tacctggaga gcgttaagaa   1560 

atacaaacgg ctggatgtgt gccgcgctaa aatgggctat atgctgcagt gaataataaa   1620 

 
           
             76  
             645  
             DNA  
             Human cytomegalovirus  
           
            76 

atgctacggc ttctgcttcg tcaccacttt cactgcctgc ttctgtgcgc ggtttgggca     60 

acgccctgtc tggcgtctcc gtggttcacg ctaacggcga accagaatcc gtccccgcca    120 

tggtctaaac tgacgtatcc caaaccgcat gacgcggcga cgttttactg tccttttctc    180 

tatccctcgc ccccacggtc cccctcgcaa ttcccggggt tccagcgggt atcaacgggt    240 

cccgagtgtc gcaacgagac cctgtatctg ctgtacaacc gggaaggcca gaccttggtg    300 

gagagaagct ccacctgggt gaaaaaggtg atctggtatc tgagcggtcg caatcagacc    360 

atcctccaac ggatgccccg aacggcttcg aaaccgagcg acggaaacgt gcagatcagc    420 

gtggaagacg ccaagatttt tggagcgcac atggtgccca agcagaccaa gctgctacgt    480 

ttcgtcgtca acgatggcac acgttatcag atgtgtgtga tgaaactgga gagctgggcc    540 

cacgtcttcc gggactacag cgtgtctttt caggtgcgat tgacgttcac cgaggccaat    600 

aaccagactt acaccttctg cacccatccc aatctcatcg tttga                    645 

 
           
             77  
             214  
             PRT  
             Human cytomegalovirus  
           
            77 

Met Leu Arg Leu Leu Leu Arg His His Phe His Cys Leu Leu Leu Cys 
1               5                   10                  15 

Ala Val Trp Ala Thr Pro Cys Leu Ala Ser Pro Trp Phe Thr Leu Thr 
            20                  25                  30 

Ala Asn Gln Asn Pro Ser Pro Pro Trp Ser Lys Leu Thr Tyr Pro Lys 
        35                  40                  45 

Pro His Asp Ala Ala Thr Phe Tyr Cys Pro Phe Leu Tyr Pro Ser Pro 
    50                  55                  60 

Pro Arg Ser Pro Ser Gln Phe Pro Gly Phe Gln Arg Val Ser Thr Gly 
65                  70                  75                  80 

Pro Glu Cys Arg Asn Glu Thr Leu Tyr Leu Leu Tyr Asn Arg Glu Gly 
                85                  90                  95 

Gln Thr Leu Val Glu Arg Ser Ser Thr Trp Val Lys Lys Val Ile Trp 
            100                 105                 110 

Tyr Leu Ser Gly Arg Asn Gln Thr Ile Leu Gln Arg Met Pro Arg Thr 
        115                 120                 125 

Ala Ser Lys Pro Ser Asp Gly Asn Val Gln Ile Ser Val Glu Asp Ala 
    130                 135                 140 

Lys Ile Phe Gly Ala His Met Val Pro Lys Gln Thr Lys Leu Leu Arg 
145                 150                 155                 160 

Phe Val Val Asn Asp Gly Thr Arg Tyr Gln Met Cys Val Met Lys Leu 
                165                 170                 175 

Glu Ser Trp Ala His Val Phe Arg Asp Tyr Ser Val Ser Phe Gln Val 
            180                 185                 190 

Arg Leu Thr Phe Thr Glu Ala Asn Asn Gln Thr Tyr Thr Phe Cys Thr 
        195                 200                 205 

His Pro Asn Leu Ile Val 
    210 

 
           
             78  
             214  
             PRT  
             Human cytomegalovirus  
           
            78 

Met Leu Arg Leu Leu Leu Arg His His Phe His Cys Leu Leu Leu Cys 
1               5                   10                  15 

Ala Val Trp Ala Thr Pro Cys Leu Ala Ser Pro Trp Phe Thr Leu Thr 
            20                  25                  30 

Ala Asn Gln Asn Pro Ser Pro Pro Trp Ser Lys Leu Thr Tyr Pro Lys 
        35                  40                  45 

Pro His Asp Ala Ala Thr Phe Tyr Cys Pro Phe Leu Tyr Pro Ser Pro 
    50                  55                  60 

Pro Arg Ser Pro Ser Gln Phe Pro Gly Phe Gln Arg Val Ser Thr Gly 
65                  70                  75                  80 

Pro Glu Cys Arg Asn Glu Thr Leu Tyr Leu Leu Tyr Asn Arg Glu Gly 
                85                  90                  95 

Gln Thr Leu Val Glu Arg Ser Ser Thr Trp Val Lys Lys Val Ile Trp 
            100                 105                 110 

Tyr Leu Ser Gly Arg Asn Gln Thr Ile Leu Gln Arg Met Pro Arg Thr 
        115                 120                 125 

Ala Ser Lys Pro Ser Asp Gly Asn Val Gln Ile Ser Val Glu Asp Ala 
    130                 135                 140 

Lys Ile Phe Gly Ala His Met Val Pro Lys Gln Thr Lys Leu Leu Arg 
145                 150                 155                 160 

Phe Val Val Asn Asp Gly Thr Arg Tyr Gln Met Cys Val Met Lys Leu 
                165                 170                 175 

Glu Ser Trp Ala His Val Phe Arg Asp Tyr Ser Val Ser Phe Gln Val 
            180                 185                 190 

Arg Leu Thr Phe Thr Glu Ala Asn Asn Gln Thr Tyr Thr Phe Cys Thr 
        195                 200                 205 

His Pro Asn Leu Ile Val 
    210 

 
           
             79  
             171  
             PRT  
             Human cytomegalovirus  
           
            79 

Met Ser Pro Lys Asn Leu Thr Pro Phe Leu Thr Ala Leu Trp Leu Leu 
1               5                   10                  15 

Leu Gly His Ser Arg Val Pro Arg Val Arg Ala Glu Glu Cys Cys Glu 
            20                  25                  30 

Phe Ile Asn Val Asn His Pro Pro Glu Arg Cys Tyr Asp Phe Lys Met 
        35                  40                  45 

Cys Asn Arg Phe Thr Val Ala Leu Arg Cys Pro Asp Gly Glu Val Cys 
    50                  55                  60 

Tyr Ser Pro Glu Lys Thr Ala Glu Ile Arg Gly Ile Val Thr Thr Met 
65                  70                  75                  80 

Thr His Ser Leu Thr Arg Gln Val Val His Asn Lys Leu Thr Ser Cys 
                85                  90                  95 

Asn Tyr Asn Pro Leu Tyr Leu Glu Ala Asp Gly Arg Ile Arg Cys Gly 
            100                 105                 110 

Lys Val Asn Asp Lys Ala Gln Tyr Leu Leu Gly Ala Ala Gly Ser Val 
        115                 120                 125 

Pro Tyr Arg Trp Ile Asn Leu Glu Tyr Asp Lys Ile Thr Arg Ile Val 
    130                 135                 140 

Gly Leu Asp Gln Tyr Leu Glu Ser Val Lys Lys His Lys Arg Leu Asp 
145                 150                 155                 160 

Val Cys Arg Ala Lys Met Gly Tyr Met Leu Gln 
                165                 170