Abstract:
This invention relates to a DNA coding for a peptide of a papilloma virus major capsid protein. Moreover, this invention deals with a papilloma virus genome containing such a DNA. Furthermore, this invention concerns proteins coded by the papilloma virus genome and virus-like particles as well as antibodies directed thereagainst and the use thereof for diagnosis, treatment and vaccination.

Description:
This is a national phase filing of the Application No. PCT/DE96/01369, which was filed with the Patent Corporation Treaty on Jul. 19, 1996. and is entitled to priority of the German Patent Application P 195 26 386.3. filed Jul. 19, 1995. 
     FIELD OF THE INVENTION 
     This invention relates to a DNA coding for a peptide of a papilloma virus major capsid protein. Moreover, this invention deals with a papilloma virus genome containing such a DNA. In addition, this invention concerns proteins coded by the papilloma virus genome and virus-like particles as well as antibodies directed against them and their use for diagnosis, treatment and vaccination. 
     BACKGROUND OF THE INVENTION 
     It is known that papilloma viruses infect the epithelium of human beings and animals. Human papilloma viruses (hereinafter referred to as HP viruses) are found in benign epithelial neoplasms, e.g. warts, condylomas in the genital zone, and malignant epithelial neoplasms, e.g. carcinomas of the skin and the uterus. Zur Hausen, 1989,  Cancer Research  49: 4677-4681. HP viruses are also considered for the growth of malignant tumors in the respiratory tract. Zur Hausen, 1976,  Cancer Research  36: 530. Besides, HP viruses are considered at least jointly responsible for the growth of squamous carcinomas of the lung. Syrjänen, 1980 , Lung  158: 131-142. 
     Papilloma viruses have an icosahedral capsid without envelope in which a circular, double-stranded DNA molecule of about 7900 bp is present. The capsid comprises a major capsid protein (L1) and a minor capsid protein (L2). Both proteins coexpressed or L1 expressed alone, result in vitro in the formation of virus-like particles Kirnbauer et al., 1993.  Journal of Virology  67:6929-6936. 
     Papilloma viruses cannot be proliferated in monolayer cell culture. Therefore, their characterization is extremely difficult, the detection of papilloma viruses already creating considerable problems. This applies especially to papilloma viruses in carcinomas of the skin. A reliable detection thereof and thus well-calculated steps taken thereagainst are not possible by now. 
     Thus, it is the object of the present invention to provide a product by which papilloma viruses can be detected, particularly in carcinomas of the skin. Furthermore, a product should be provided to be able to take therapeutic steps against these papilloma viruses. 
     SUMMARY OF THE INVENTION 
     This invention relates to a DNA coding for a peptide of a papilloma virus major capsid protein. Moreover, this invention deals with a papilloma virus genome containing such a DNA. Furthermore, this invention concerns proteins coded by the papilloma virus genome and virus-like particles as well as antibodies directed thereagainst and the use thereof for diagnosis treatment and vaccination. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 shows the base sequence and the amino acid sequence, derived therefrom, of a DNA coding for a peptide of L1 of a papilloma virus. This DNA was deposited as plasmid VS19-6 with DSM ( Deutsche Sammlung von Mikroorganismen und Zellkulturen  under DSM 10104 on Jul. 11, 1995. 
     FIG. 2 shows the base sequence and the amino acid sequence, derived therefrom, of a DNA coding for a peptide of L1 of a papilloma virus. This DNA was deposited as plasmid VS200-1 with DSM under DSM 10096 on Jul. 11, 1995. 
     FIG. 3 shows the base sequence and the amino acid sequence, derived therefrom, of a DNA coding for a peptide of L1 of a papilloma virus. This DNA was deposited as plasmid VS201-1 with DSM under DSM 10097 on Jul. 11, 1995. 
     FIG. 4 shows the base sequence and the amino acid sequence, derived therefrom, of a DNA coding for a peptide of L1 of a papilloma virus. This DNA was deposited as plasmid VS202-8 with DSM under DSM 10098 on Jul. 11, 1995. 
     FIG. 5 shows the base sequence and the amino acid sequence, derived therefrom, of a DNA coding for a peptide of L1 of a papilloma virus. This DNA was deposited as plasmid VS203-2 with DSM under DSM 10099 on Jul. 11, 1995. 
     FIG. 6 shows the base sequence and the amino acid sequence, derived therefrom, of a DNA coding for a peptide of L1 of a papilloma virus. This DNA was deposited as plasmid VS204-4 with DSM under DSM 10100 on Jul. 11, 1995. 
     FIG. 7 shows the base sequence and the amino acid sequence, derived therefrom, of a DNA coding for a peptide of L1 of a papilloma virus. This DNA was deposited as plasmid VS205-1 with DSM under DSM 10101 on Jul. 11, 1995. 
     FIG. 8 shows the base sequence and the amino acid sequence, derived therefrom, of a DNA coding for a peptide of L1 of a papilloma virus. This DNA was deposited as plasmid VS206-2 with DSM under DSM 10109 on Jul. 13, 1995. 
     FIG. 9 shows the base sequence and the amino acid sequence, derived therefrom, of a DNA coding for a peptide of L1 of a papilloma virus. This DNA was deposited as plasmid VS207-22 with DSM under DSM 10102 on Jul. 11, 1995. 
     FIG. 10 shows the base sequence and the amino acid sequence, derived therefrom, of a DNA coding for a peptide of L1 of a papilloma virus. This DNA was deposited as plasmid VS208-1 with DSM under DSM 10103 on Jul. 11, 1995. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     It is the object of the present invention to provide a product by which papilloma viruses can be detected, particularly in carcinomas of the skin. Furthermore, a product is provided which enables to take therapeutic steps against these papilloma viruses. 
     Accordingly, the subject matter of the invention relates to a DNA coding for a peptide of a papilloma virus major capsid protein (L1), the peptide comprising the amino acid sequence of FIG. 1, FIG. 2, FIG. 3, FIG. 4, FIG. 5, FIG. 6, FIG. 7, FIG. 8, FIG. 9 or FIG. 10 or an amino acid sequence differing: therefrom by one or more amino acids. 
     A further subject matter of the invention relates to a DNA coding for a peptide of a papilloma virus major capsid protein, the DNA comprising the base sequence of FIG. 1, FIG. 2, FIG. 3, FIG. 4, FIG. 5, FIG. 6, FIG. 7, FIG. 8, FIG. 9 or FIG. 10 or a base sequence differing therefrom by one or more base pairs. 
     The above DNA has the following sequence homology with respect to known papilloma viruses: 
     DNA of FIG.  1 : 69.1% with respect to HP virus 65 
     DNA of FIG.  2 : 80.7% with respect to HP virus 24 
     DNA of FIG.  3 : 69.4% with respect to HP virus 48 
     DNA of FIG.  4 : 66.3 % with respect to HIP virus 48 
     DNA of FIG.  5 : 66.9% with respect to HP virus 65 
     DNA of FIG.  6 : 66.4% with respect to HP virus 65 
     DNA of FIG.  7 : 69.1% with respect to HP virus 4 
     DNA of FIG.  8 : 68.7% with respect to HP virus 48 
     DNA of FIG.  9 : 76.6% with respect to HP virus 48 
     DNA of FIG.  10 : 81.8% with respect to HP virus 68 
     According to the invention, the above DNA can be present in a vector and expression vector, respectively. A person skilled in the art is familiar with examples thereof. In the case of an expression vector for  E. coli , these are e.g. pGEMEX, pUC derivatives, pGEM-T and pGEX-2T. For the expression in yeast e.g. pY00 and Ycpad1 have to be mentioned, while for the expression in animal cells e.g. pKCR, pEF-BOS, cDM8 and pCEV4 have to be indicated. 
     The person skilled in the art knows suitable cells to express the above DNA present in an expression vector. Examples of such cells comprise the  E. Coli  strains HB101, DH1, ×776, JM101, JM 109, and XL1-Blue, the yeast strain  Saccharomyces cerevisiae  and the animal cells L, NH-3T3, FM3A, CHO, COS, Vero, and HeLa. 
     The person skilled in the art knows in which way the above DNA has to be inserted in an expression vector. He is also familiar with the fact that the above DNA can be inserted in connection with a DNA coding for another protein and peptide, respectively, so that the above DNA can be expressed in the form of a fusion protein. 
     A further subject matter of the invention relates to a papilloma virus genome which comprises the above DNA. The expression “papilloma” virus genome” also comprises an incomplete genome, i.e. fragments of a papilloma virus genome, which comprise the above DNA. This may be e.g. a DNA coding for L1 or a portion thereof. 
     A common process can be used for the provision of the above papilloma virus genome, which comprises the following processing steps: 
     (a) isolation of the total DNA from a biopsy of epithelial neoplasm, 
     (b) hybridization of the total DNA of (a) with the above DNA so as to detect a papilloma virus genome included in the total DNA of (a), and 
     (c) cloning of the total DNA of (a) containing the papilloma virus genome, in a vector and optionally subcloning the resulting clone, all processing steps originating from common DNA recombination technique. 
     As far as the isolation, hybridization and cloning of cell DNA is concerned, reference is made by way of supplement to Sambrook et al.,  Molecular Cloning, A Laboratory Manual , second edition, Cold Spring Harbor Laboratory (1989). 
     The expression “epithelial neoplasm” comprises any neoplasms of epithelium in man and animal. Examples of such neoplasms are warts, condylomas in the genital zone and carcinomas of the skin. The latter are used preferably to isolate the above papilloma virus genome. 
     The expression “vector” comprises any vectors suitable for cloning chromosomal DNA and extrachromosomal DNA, respectively. Examples of such vectors are cosmids such as pWE15 and Super Cos1, and phages such as λ-phages, e.g. λZAP expression vector, λZAPII vector and λgt10 vector. In the present case, λ-phages are used preferably. The above vectors are known and obtainable from the company of Stratagene. 
     Papilloma virus genomes according to the invention may be present in integrated form in chromosomal DNA or in extrachromosomal fashion. The person skilled in the art is familiar with processes serving the clarification thereof. He also knows processes serving for finding out the optimum restriction enzymes for cloning the papilloma virus genomes. He will orient himself by genomes of known papilloma viruses. In particular, the person skilled in the art will pay corresponding attention to the above-mentioned HP viruses. 
     The provision of a papilloma virus genome referred to as VS19-6 is described by way of example. For this purpose, the total DNA is isolated from a biopsy of a squamous cell carcinoma, cleaved by BamHI and separated eletrophoretically in an agarose gel. The agarose gel is then subjected to a blotting method so as to transfer the DNA to a nitrocellulose membrane. It is inserted in a hybridization method in which the DNA of FIG. 1 is used as labeled sample, optionally in combination with a DNA of HP virus 65. Hybridization with the papilloma virus DNA present in the total DNA is obtained. 
     Moreover, the above total DNA cleaved by BamHI is cloned in a λ-phage. The corresponding clones, i.e. the clones containing the papilloma virus DNA are identified by hybridization with the DNA of FIG. 1, optionally in combination with a DNA of the HP virus 65. The insert of these clones is then subjected to a further cloning in a plasmid vector so as to obtain a clone which contains the papilloma virus genome VS19-6-G. The genome is confirmed by sequencing. 
     Further papilloma virus genomes are provided analogously. They are designated in accordance with the DNAs used for their provision, namely by: VS200-1-G, VS201-1-G, VS202-8-G, VS203-2-G, VS204-4-G, VS205-1-G, VS206-2-G, VS207-22-G and VS208-1-G, respectively. 
     A further subject matter of the invention relates to a protein which is coded by the above papilloma virus genome. Such a protein is e.g. a major capsid protein (L1) or a minor capsid protein (L2). An above protein is prepared as usual. The preparation of L1 and L2, respectively, of the papilloma virus genome VS19-6-G is described by way of example. For this purpose, the HP virus 65 related to the DNA of FIG. 1 is used. The full sequence and the position of individual DNA regions coding for proteins are known in connection therewith. These DNAs are identified on the papilloma virus genome VS19-6-G by parallel restriction cleavages of both genomes and subsequent hybridization with various fragments concerning the DNA encoding L1 and L2, respectively. They are confirmed by sequencing. The DNA coding for L1 is referred to as VS19-6-G-L1 DNA and the DNA coding for L2 is referred to as VS19-6-G-L2 DNA. 
     Furthermore, the DNA coding for L1 and L2, respectively, is inserted in an expression vector. Examples thereof are mentioned above for  E. coli , yeast and animal cells. In this connection, reference is made to the vector pGEX-2T as regards the expression in  E. coli  by way of supplement. Kirnbauer et al., supra. Having inserted the VS19-6-G-L1 DNA and VS19-6-G-L2 DNA, one obtains pGEX-2T-VS19-6-G-L1 and pGEX-2T-VS19-6-G-L2, respectively. After transforming  E. coli , these expression vectors express a glutathione S transferase L1 fusion protein and glutathione S transferase L2 fusion protein, respectively. The proteins are purified as usual. 
     The bacculovirus system and vaccinia virus system, respectively, is mentioned for a further expression of the above DNA encoding L1 and L2, respectively. Expression vectors usable for this purpose are e.g. pEV mod. and pSynwtVI −  for the bacculovirus system. Kirnbauer et al., supra. Especially vectors with the vaccinia virus “early” (p7.5k) promoter and “late” (Psynth, p11K) promoter, respectively, have to be mentioned for the vaccinia virus system. Hagensee et al., 1993  Journal of Virology , 67:315-322. The bacculovirus system is preferred in the present case. Having inserted the above DNA encoding L1 and L2, respectively, in pEV mod., one obtains pEVmod.-VS19-6-G-L1 and pEVmod.-VS19-6-G-L2, respectively. 
     The former expression vector as such or both expression vectors jointly lead to the formation of virus-like particles after infection of SF-9 insect cells. In the former case, such a particle comprises an L1 protein, while in the latter case it contains an L2 protein in addition to an L1 protein. 
     A virus-like particle of the latter case is also obtained by inserting the above VS19-6-G-L1 and VS19-6-G-L2 DNAs jointly in the expression vector pSynwtVI −  and using the resulting pSynwtVI-VS19-6-G-L1/L2 for the infection of SF-9 insect cells. The above virus-like particles are purified as usual. They also represent a subject matter of the invention. 
     A further subject matter of the invention relates to an antibody directed against an above protein and virus-like particle, respectively. The preparation thereof is made as usual. It is described by way of example for the preparation of an antibody which is directed against a virus-like particle comprising L1 of VS19-6-G. For this purpose, the virus-like particle is injected subcutaneously into BALB/c mice. This injection is repeated at intervals of 3 weeks each. About 2 weeks after the last injection, the serum containing the antibody is isolated and tested as usual. 
     In a preferred embodiment, the antibody is a monoclonal antibody. For its preparation, spleen cells are removed from the mice after the above fourth injection and fused with myeloma cells as usual. The further cloning also takes place according to known methods. 
     By means of the present invention it is possible to detect papilloma viruses, particularly in carcinomas of the skin. For this purpose, the DNA according to the invention can be used as such or when comprised by a further DNA. The latter may also be a papilloma virus genome or a portion thereof. 
     The present invention also enables the provision of formerly unknown papilloma viruses. They are found especially in carcinomas of the skin. In addition, the invention supplies proteins and virus-like particles which originate from these papilloma viruses. Moreover, antibodies are provided which are directed against these proteins and particles, respectively. 
     The present invention also enables to take diagnostic and therapeutic steps in the case of papilloma virus diseases. Moreover, it supplies the possibility of building up a vaccine against papilloma virus infections. Thus, the present invention represents a break-through in the field of papilloma virus research. 
     The below examples explain the invention in more detail. The following preparations and examples are given to enable those skilled in the art to more clearly understand and to practice the present invention. The present invention, however is not limited in scope by the exemplified embodiments, which are intended as illustrations of single aspects of the invention only, and methods which are functionally equivalent are within the scope of the invention. Indeed, various modifications of the invention in addition to those described herein will become apparent to those skilled in the art from the foregoing description and accompanying drawings. Such modifications are intended to fall within the scope of the appended claims. 
     EXAMPLES 
     Example 1 
     Identification of the Papilloma Virus Genome VS19-6-G 
     The total DNA is isolated from a biopsy of a squamous cell carcinoma of an immuno-suppressed person. 10 μg of this DNA are cleaved by the restriction enzyme BamHI and separated electrophoretically in a 0.5% agarose gel. At the same time, 10 μg of the above DNA, which was not cleaved, is also separated. The agarose gel is subjected to a blotting method so as to transfer the DNA from the agarose gel to a nitrocellulose membrane. It is employed in a hybridization method in which the above DNA of FIG. 1 is used in combination with the HP virus-65 DNA as  32 P-labeled sample. Hybridization with the blotted DNA is obtained. 
     The person skilled in the field of DNA recombination technique is familiar with the above methods. Reference is made to Sambrook et al., supra, by way of supplement. 
     Example 2 
     Cloning of the Papilloma Virus Genome VS19-6-G 
     The biopsy DNA obtained from Example 1 is cleaved by the restriction enzyme BamHI. The resulting fragments are used in a ligase reaction in which the dephosphorylated vector λZAP express cleaved by BamHI is also present. The resulting recombinant DNA molecules are packed in bacteriophages, and they are used for infecting bacteria. For these processing steps, the ZAP express vector kit offered by the company of Stratagene is used. The resulting phage plaques are then subjected to a hybridization process which uses the  32 P-labeled DNA of FIG. 1 employed in Example 1 in combination with  32 P-labeled HP virus-65 DNA. Hybridization with corresponding phage plaques is obtained. The BamHI fragments of VS19-6-G are isolated therefrom and used in a further ligase reaction together with a BamHI-cleaved, dephosphorylated plasmid vector, pBluescript. The resulting recombinant DNA molecules are used for transforming bacteria,  E. coli  XL1-Blue. By restriction cleavages and hybridization with the above DNA samples, respectively, a bacterial clone containing the papilloma virus genome VS19-6-G is identified. The plasmid of this bacterial clone is referred to as pBlue-VS19-6-G. 
     All references cited within the body of the instant specification are hereby incorporated by reference in their entirety. 
     
       
         
           
             30 
           
           
             1 
             419 
             DNA 
             Papilloma virus 
             
               CDS 
               (1)...(417) 
             
           
            1
gga tcc atg cag gat ggt gac atg tgt gat ata gga ttc gga gct tgc       48
Gly Ser Met Gln Asp Gly Asp Met Cys Asp Ile Gly Phe Gly Ala Cys
 1               5                   10                  15
aat ttc agg gca ttt cag caa gat agg tca ggt gtt cct tta gat ata       96
Asn Phe Arg Ala Phe Gln Gln Asp Arg Ser Gly Val Pro Leu Asp Ile
             20                  25                  30
gta gat agt act tgc aag tat cca gac ttt ttg aaa atg aca aaa gac      144
Val Asp Ser Thr Cys Lys Tyr Pro Asp Phe Leu Lys Met Thr Lys Asp
         35                  40                  45
aag tat ggt gat gaa tgc ttc ttt ttt ggt cgt cga gag cag ttg tat      192
Lys Tyr Gly Asp Glu Cys Phe Phe Phe Gly Arg Arg Glu Gln Leu Tyr
     50                  55                  60
gca agg cat tat ttt acc aga gca ggc aca ata ggt gat tct att cca      240
Ala Arg His Tyr Phe Thr Arg Ala Gly Thr Ile Gly Asp Ser Ile Pro
 65                  70                  75                  80
acg cca tat cag gaa tct gaa ttt tac aga tct cca cag gat agc cag      288
Thr Pro Tyr Gln Glu Ser Glu Phe Tyr Arg Ser Pro Gln Asp Ser Gln
                 85                  90                  95
gct cag aat aat gtg gat tct cac att tat gta gcc act cct agt ggt      336
Ala Gln Asn Asn Val Asp Ser His Ile Tyr Val Ala Thr Pro Ser Gly
            100                 105                 110
tct tta act agc agt gat gct cag ctg ttt aac aga cct tat tgg ctc      384
Ser Leu Thr Ser Ser Asp Ala Gln Leu Phe Asn Arg Pro Tyr Trp Leu
        115                 120                 125
caa aat gct caa ggt acc aat aac gga atg gat cc                       419
Gln Asn Ala Gln Gly Thr Asn Asn Gly Met Asp
    130                 135 
           
             2 
             139 
             PRT 
             Papilloma virus 
           
            2
Gly Ser Met Gln Asp Gly Asp Met Cys Asp Ile Gly Phe Gly Ala Cys
 1               5                  10                  15
Asn Phe Arg Ala Phe Gln Gln Asp Arg Ser Gly Val Pro Leu Asp Ile
            20                  25                  30
Val Asp Ser Thr Cys Lys Tyr Pro Asp Phe Leu Lys Met Thr Lys Asp
        35                  40                  45
Lys Tyr Gly Asp Glu Cys Phe Phe Phe Gly Arg Arg Glu Gln Leu Tyr
    50                  55                  60
Ala Arg His Tyr Phe Thr Arg Ala Gly Thr Ile Gly Asp Ser Ile Pro
65                  70                  75                  80
Thr Pro Tyr Gln Glu Ser Glu Phe Tyr Arg Ser Pro Gln Asp Ser Gln
                85                  90                  95
Ala Gln Asn Asn Val Asp Ser His Ile Tyr Val Ala Thr Pro Ser Gly
            100                 105                 110
Ser Leu Thr Ser Ser Asp Ala Gln Leu Phe Asn Arg Pro Tyr Trp Leu
        115                 120                 125
Gln Asn Ala Gln Gly Thr Asn Asn Gly Met Asp
    130                 135 
           
             3 
             419 
             DNA 
             Papilloma virus 
           
            3
ggatccattc cgttattggt accttgagca ttttggagcc aataaggtct gttaaacagc     60
tgagcatcac tgctagttaa agaaccacta ggagtggcta cataaatgtg agaatccaca    120
ttattctgag cctggctatc ctgtggagat ctgtaaaatt cagattcctg atatggcgtt    180
ggaatagaat cacctattgt gcctgctctg gtaaaataat gccttgcata caactgctct    240
cgacgaccaa aaaagaagca ttcatcacca tacttgtctt ttgtcatttt caaaaagtct    300
ggatacttgc aagtactatc tactatatct aaaggaacac ctgacctatc ttgctgaaat    360
gccctgaaat tgcaagctcc gaatcctata tcacacatgt caccatcctg catggatcc     419 
           
             4 
             434 
             DNA 
             Papilloma virus 
             
               CDS 
               (1)...(432) 
             
           
            4
gga tcc atg gag gac ggt gag atg gca gac ata gga tat ggt aat ctt       48
Gly Ser Met Glu Asp Gly Glu Met Ala Asp Ile Gly Tyr Gly Asn Leu
 1               5                   10                  15
aat ttt aaa gct tta cag gaa aat agg cct gat gtt agt ctt gat att       96
Asn Phe Lys Ala Leu Gln Glu Asn Arg Pro Asp Val Ser Leu Asp Ile
             20                  25                  30
gtc aat gaa acc tgc aaa tat cca gat ttt ttg aag atg caa aat gat      144
Val Asn Glu Thr Cys Lys Tyr Pro Asp Phe Leu Lys Met Gln Asn Asp
         35                  40                  45
gtt tat gga gac tcc tgt ttc ttt ttt gct cgt aga gag caa tgt tat      192
Val Tyr Gly Asp Ser Cys Phe Phe Phe Ala Arg Arg Glu Gln Cys Tyr
     50                  55                  60
gcc aga cac ttt ttt gta aga ggt ggc aac gta ggg gat gac att cct      240
Ala Arg His Phe Phe Val Arg Gly Gly Asn Val Gly Asp Asp Ile Pro
 65                  70                  75                  80
ggt gaa caa ata gac gca ggc aca tat aaa aat gat ttt tac att cca      288
Gly Glu Gln Ile Asp Ala Gly Thr Tyr Lys Asn Asp Phe Tyr Ile Pro
                 85                  90                  95
gga gca tca ggt cag aca caa aat aaa ata ggt aac tcc atg tat ttc      336
Gly Ala Ser Gly Gln Thr Gln Asn Lys Ile Gly Asn Ser Met Tyr Phe
            100                 105                 110
cca aca gtt agt ggc tca tta gtg tct agt gat gct cag ctg ttt aat      384
Pro Thr Val Ser Gly Ser Leu Val Ser Ser Asp Ala Gln Leu Phe Asn
        115                 120                 125
agg ccc tac tgg ctc caa cgc gca cag ggc cac aac aac ggc gtg gat      432
Arg Pro Tyr Trp Leu Gln Arg Ala Gln Gly His Asn Asn Gly Val Asp
    130                 135                 140
cc                                                                   434 
           
             5 
             144 
             PRT 
             Papilloma virus 
           
            5
Gly Ser Met Glu Asp Gly Glu Met Ala Asp Ile Gly Tyr Gly Asn Leu
 1               5                  10                  15
Asn Phe Lys Ala Leu Gln Glu Asn Arg Pro Asp Val Ser Leu Asp Ile
            20                  25                  30
Val Asn Glu Thr Cys Lys Tyr Pro Asp Phe Leu Lys Met Gln Asn Asp
        35                  40                  45
Val Tyr Gly Asp Ser Cys Phe Phe Phe Ala Arg Arg Glu Gln Cys Tyr
    50                  55                  60
Ala Arg His Phe Phe Val Arg Gly Gly Asn Val Gly Asp Asp Ile Pro
65                  70                  75                  80
Gly Glu Gln Ile Asp Ala Gly Thr Tyr Lys Asn Asp Phe Tyr Ile Pro
                85                  90                  95
Gly Ala Ser Gly Gln Thr Gln Asn Lys Ile Gly Asn Ser Met Tyr Phe
            100                 105                 110
Pro Thr Val Ser Gly Ser Leu Val Ser Ser Asp Ala Gln Leu Phe Asn
        115                 120                 125
Arg Pro Tyr Trp Leu Gln Arg Ala Gln Gly His Asn Asn Gly Val Asp
    130                 135                 140 
           
             6 
             434 
             DNA 
             Papilloma virus 
           
            6
ggatccacgc cgttgttgtg gccctgtgcg cgttggagcc agtagggcct attaaacagc     60
tgagcatcac tagacactaa tgagccacta actgttggga aatacatgga gttacctatt    120
ttattttgtg tctgacctga tgctcctgga atgtaaaaat catttttata tgtgcctgcg    180
tctatttgtt caccaggaat gtcatcccct acgttgccac ctcttacaaa aaagtgtctg    240
gcataacatt gctctctacg agcaaaaaag aaacaggagt ctccataaac atcattttgc    300
atcttcaaaa aatctggata tttgcaggtt tcattgacaa tatcaagact aacatcaggc    360
ctattttcct gtaaagcttt aaaattaaga ttaccatatc ctatgtctgc catctcaccg    420
tcctccatgg atcc                                                      434 
           
             7 
             410 
             DNA 
             Papilloma virus 
             
               CDS 
               (1)...(408) 
             
           
            7
gga tcc cta gag gat ggt gat atg ggt gat ata gga ttt ggg cat gct       48
Gly Ser Leu Glu Asp Gly Asp Met Gly Asp Ile Gly Phe Gly His Ala
 1               5                   10                  15
aat ttt agc cgt tta caa gaa gat aaa gca ggt gtg cca tta gaa tta       96
Asn Phe Ser Arg Leu Gln Glu Asp Lys Ala Gly Val Pro Leu Glu Leu
             20                  25                  30
gtg gac act ttt agt ata tgg cct gac ttt tta cgc atg acc agt gat      144
Val Asp Thr Phe Ser Ile Trp Pro Asp Phe Leu Arg Met Thr Ser Asp
         35                  40                  45
ata tat gga gat gct gtg ttt ttt tgg gga aag cga gaa cat atg ttt      192
Ile Tyr Gly Asp Ala Val Phe Phe Trp Gly Lys Arg Glu His Met Phe
     50                  55                  60
gcc aga cat tta tgg gca aga gct gga act atg ggc gac gct att cca      240
Ala Arg His Leu Trp Ala Arg Ala Gly Thr Met Gly Asp Ala Ile Pro
 65                  70                  75                  80
gat aat aat gca gag ttt ttt ctg cat ccc aat ggt gca cct caa aat      288
Asp Asn Asn Ala Glu Phe Phe Leu His Pro Asn Gly Ala Pro Gln Asn
                 85                  90                  95
aag tta gcc tca ttt gct tat ttt cca aca cct agt ggt tct ctt aat      336
Lys Leu Ala Ser Phe Ala Tyr Phe Pro Thr Pro Ser Gly Ser Leu Asn
            100                 105                 110
acc agt gat aat caa ttg ttt aat aag ccg tat tgg ttg cga aaa gct      384
Thr Ser Asp Asn Gln Leu Phe Asn Lys Pro Tyr Trp Leu Arg Lys Ala
        115                 120                 125
cag ggc acc aac aat ggg atg gat cc                                   410
Gln Gly Thr Asn Asn Gly Met Asp
    130                 135 
           
             8 
             136 
             PRT 
             Papilloma virus 
           
            8
Gly Ser Leu Glu Asp Gly Asp Met Gly Asp Ile Gly Phe Gly His Ala
 1               5                  10                  15
Asn Phe Ser Arg Leu Gln Glu Asp Lys Ala Gly Val Pro Leu Glu Leu
            20                  25                  30
Val Asp Thr Phe Ser Ile Trp Pro Asp Phe Leu Arg Met Thr Ser Asp
        35                  40                  45
Ile Tyr Gly Asp Ala Val Phe Phe Trp Gly Lys Arg Glu His Met Phe
    50                  55                  60
Ala Arg His Leu Trp Ala Arg Ala Gly Thr Met Gly Asp Ala Ile Pro
65                  70                  75                  80
Asp Asn Asn Ala Glu Phe Phe Leu His Pro Asn Gly Ala Pro Gln Asn
                85                  90                  95
Lys Leu Ala Ser Phe Ala Tyr Phe Pro Thr Pro Ser Gly Ser Leu Asn
            100                 105                 110
Thr Ser Asp Asn Gln Leu Phe Asn Lys Pro Tyr Trp Leu Arg Lys Ala
        115                 120                 125
Gln Gly Thr Asn Asn Gly Met Asp
    130                 135 
           
             9 
             410 
             DNA 
             Papilloma virus 
           
            9
ggatccatcc cattgttggt gccctgagct tttcgcaacc aatacggctt attaaacaat     60
tgattatcac tggtattaag agaaccacta ggtgttggaa aataagcaaa tgaggctaac    120
ttattttgag gtgcaccatt gggatgcaga aaaaactctg cattattatc tggaatagcg    180
tcgcccatag ttccagctct tgcccataaa tgtctggcaa acatatgttc tcgctttccc    240
caaaaaaaca cagcatctcc atatatatca ctggtcatgc gtaaaaagtc aggccatata    300
ctaaaagtgt ccactaattc taatggcaca cctgctttat cttcttgtaa acggctaaaa    360
ttagcatgcc caaatcctat atcacccata tcaccatcct ctagggatcc               410 
           
             10 
             437 
             DNA 
             Papilloma virus 
             
               CDS 
               (1)...(435) 
             
           
            10
gga tcc att gag gat gcg gat atg agt gat ata gga ttt gga gct gtg       48
Gly Ser Ile Glu Asp Ala Asp Met Ser Asp Ile Gly Phe Gly Ala Val
 1               5                   10                  15
aat ttt agc act ttc tct gaa agc cgg gct gat gca cct tta gaa tta       96
Asn Phe Ser Thr Phe Ser Glu Ser Arg Ala Asp Ala Pro Leu Glu Leu
             20                  25                  30
atc aat tct att agt aaa tgg cct gat ttt att caa atg tct aag gat      144
Ile Asn Ser Ile Ser Lys Trp Pro Asp Phe Ile Gln Met Ser Lys Asp
         35                  40                  45
att tat ggc gat aga atg ttt ttc ttt gga aaa cgt gag cag atg tat      192
Ile Tyr Gly Asp Arg Met Phe Phe Phe Gly Lys Arg Glu Gln Met Tyr
     50                  55                  60
gca aga cac aca ttt tgt aaa gat ggt gct gtg gga gat gct att cca      240
Ala Arg His Thr Phe Cys Lys Asp Gly Ala Val Gly Asp Ala Ile Pro
 65                  70                  75                  80
gaa aat tta aat aat gat gag gat gtt cat cat agg ttt tta tta aat      288
Glu Asn Leu Asn Asn Asp Glu Asp Val His His Arg Phe Leu Leu Asn
                 85                  90                  95
cct aag cct gac gca cca cca tat tca aac tta gga aac agt act tac      336
Pro Lys Pro Asp Ala Pro Pro Tyr Ser Asn Leu Gly Asn Ser Thr Tyr
            100                 105                 110
ttt cct atg cca agt ggt tca tta gtt agt agt gaa act caa tta ttt      384
Phe Pro Met Pro Ser Gly Ser Leu Val Ser Ser Glu Thr Gln Leu Phe
        115                 120                 125
aac aga cca ttt tgg cta cat cga gca cag ggc acc aat aac ggc atg      432
Asn Arg Pro Phe Trp Leu His Arg Ala Gln Gly Thr Asn Asn Gly Met
    130                 135                 140
gat cc                                                               437
Asp
145 
           
             11 
             145 
             PRT 
             Papilloma virus 
           
            11
Gly Ser Ile Glu Asp Ala Asp Met Ser Asp Ile Gly Phe Gly Ala Val
 1               5                  10                  15
Asn Phe Ser Thr Phe Ser Glu Ser Arg Ala Asp Ala Pro Leu Glu Leu
            20                  25                  30
Ile Asn Ser Ile Ser Lys Trp Pro Asp Phe Ile Gln Met Ser Lys Asp
        35                  40                  45
Ile Tyr Gly Asp Arg Met Phe Phe Phe Gly Lys Arg Glu Gln Met Tyr
    50                  55                  60
Ala Arg His Thr Phe Cys Lys Asp Gly Ala Val Gly Asp Ala Ile Pro
65                  70                  75                  80
Glu Asn Leu Asn Asn Asp Glu Asp Val His His Arg Phe Leu Leu Asn
                85                  90                  95
Pro Lys Pro Asp Ala Pro Pro Tyr Ser Asn Leu Gly Asn Ser Thr Tyr
            100                 105                 110
Phe Pro Met Pro Ser Gly Ser Leu Val Ser Ser Glu Thr Gln Leu Phe
        115                 120                 125
Asn Arg Pro Phe Trp Leu His Arg Ala Gln Gly Thr Asn Asn Gly Met
    130                 135                 140
Asp
145 
           
             12 
             437 
             DNA 
             Papilloma virus 
           
            12
ggatccatgc cgttattggt gccctgtgct cgatgtagcc aaaatggtct gttaaataat     60
tgagtttcac tactaactaa tgaaccactt ggcataggaa agtaagtact gtttcctaag    120
tttgaatatg gtggtgcgtc aggcttagga tttaataaaa acctatgatg aacatcctca    180
tcattattta aattttctgg aatagcatct cccacagcac catctttaca aaatgtgtgt    240
cttgcataca tctgctcacg ttttccaaag aaaaacattc tatcgccata aatatcctta    300
gacatttgaa taaaatcagg ccatttacta atagaattga ttaattctaa aggtgcatca    360
gcccggcttt cagagaaagt gctaaaattc acagctccaa atcctatatc actcatatcc    420
gcatcctcaa tggatcc                                                   437 
           
             13 
             416 
             DNA 
             Papilloma virus 
             
               CDS 
               (1)...(414) 
             
           
            13
gga tcc atg gag gat ggt gaa atg ggc gac ata ggc ttt gga gcc ttt       48
Gly Ser Met Glu Asp Gly Glu Met Gly Asp Ile Gly Phe Gly Ala Phe
 1               5                   10                  15
aat ttt aaa gcc cta cag aaa gat cgt gct ggt gtt agt tta gat tta       96
Asn Phe Lys Ala Leu Gln Lys Asp Arg Ala Gly Val Ser Leu Asp Leu
             20                  25                  30
gtt gat aca ttc agt ata tgg cca gac ttt tta aaa atg act aat gat      144
Val Asp Thr Phe Ser Ile Trp Pro Asp Phe Leu Lys Met Thr Asn Asp
         35                  40                  45
ata tat ggt gac agt atc ttt ttt tat ggt aaa aga gaa cag cta ttt      192
Ile Tyr Gly Asp Ser Ile Phe Phe Tyr Gly Lys Arg Glu Gln Leu Phe
     50                  55                  60
agt aga cac ttg tgg gcc cgc gca gga acg gct gga gat gcc att cca      240
Ser Arg His Leu Trp Ala Arg Ala Gly Thr Ala Gly Asp Ala Ile Pro
 65                  70                  75                  80
tct cct gat aac aaa aat cta ata ttt cag ggt gat gat gca gtg cca      288
Ser Pro Asp Asn Lys Asn Leu Ile Phe Gln Gly Asp Asp Ala Val Pro
                 85                  90                  95
caa aag act gct ggg tct ttt act tat ttt agt gcc cct agt ggg tca      336
Gln Lys Thr Ala Gly Ser Phe Thr Tyr Phe Ser Ala Pro Ser Gly Ser
            100                 105                 110
tta aca act agt gat tct cag tta ttt aat agg cca tat tgg tta aga      384
Leu Thr Thr Ser Asp Ser Gln Leu Phe Asn Arg Pro Tyr Trp Leu Arg
        115                 120                 125
aga gct caa ggt acc aac aac ggt gtg gat cc                           416
Arg Ala Gln Gly Thr Asn Asn Gly Val Asp
    130                 135 
           
             14 
             138 
             PRT 
             Papilloma virus 
           
            14
Gly Ser Met Glu Asp Gly Glu Met Gly Asp Ile Gly Phe Gly Ala Phe
 1               5                  10                  15
Asn Phe Lys Ala Leu Gln Lys Asp Arg Ala Gly Val Ser Leu Asp Leu
            20                  25                  30
Val Asp Thr Phe Ser Ile Trp Pro Asp Phe Leu Lys Met Thr Asn Asp
        35                  40                  45
Ile Tyr Gly Asp Ser Ile Phe Phe Tyr Gly Lys Arg Glu Gln Leu Phe
    50                  55                  60
Ser Arg His Leu Trp Ala Arg Ala Gly Thr Ala Gly Asp Ala Ile Pro
65                  70                  75                  80
Ser Pro Asp Asn Lys Asn Leu Ile Phe Gln Gly Asp Asp Ala Val Pro
                85                  90                  95
Gln Lys Thr Ala Gly Ser Phe Thr Tyr Phe Ser Ala Pro Ser Gly Ser
            100                 105                 110
Leu Thr Thr Ser Asp Ser Gln Leu Phe Asn Arg Pro Tyr Trp Leu Arg
        115                 120                 125
Arg Ala Gln Gly Thr Asn Asn Gly Val Asp
    130                 135 
           
             15 
             416 
             DNA 
             Papilloma virus 
           
            15
ggatccacac cgttgttggt accttgagct cttcttaacc aatatggcct attaaataac     60
tgagaatcac tagttgttaa tgacccacta ggggcactaa aataagtaaa agacccagca    120
gtcttttgtg gcactgcatc atcaccctga aatattagat ttttgttatc aggagatgga    180
atggcatctc cagccgttcc tgcgcgggcc cacaagtgtc tactaaatag ctgttctctt    240
ttaccataaa aaaagatact gtcaccatat atatcattag tcatttttaa aaagtctggc    300
catatactga atgtatcaac taaatctaaa ctaacaccag cacgatcttt ctgtagggct    360
ttaaaattaa aggctccaaa gcctatgtcg cccatttcac catcctccat ggatcc        416 
           
             16 
             413 
             DNA 
             Papilloma virus 
             
               CDS 
               (1)...(411) 
             
           
            16
gga tcc atg gag gac ggt gag atg agt gat aca ggt ttt ggt gct atg       48
Gly Ser Met Glu Asp Gly Glu Met Ser Asp Thr Gly Phe Gly Ala Met
 1               5                   10                  15
aat ttt gat aat cta tgc gag gac aga gct tca ttt cct tta gac att       96
Asn Phe Asp Asn Leu Cys Glu Asp Arg Ala Ser Phe Pro Leu Asp Ile
             20                  25                  30
ata aat gag acc tcc aag tgg cct gat ttt cta aaa atg aat aaa gat      144
Ile Asn Glu Thr Ser Lys Trp Pro Asp Phe Leu Lys Met Asn Lys Asp
         35                  40                  45
cct tat gga gat cat ata ttt ttc ttt ggt tta cga gag cag tta tat      192
Pro Tyr Gly Asp His Ile Phe Phe Phe Gly Leu Arg Glu Gln Leu Tyr
     50                  55                  60
tcc aga cat cat ggt gct cgg gga gga aaa atg gga gat act att cca      240
Ser Arg His His Gly Ala Arg Gly Gly Lys Met Gly Asp Thr Ile Pro
 65                  70                  75                  80
gaa aat aca gca ggc gaa tat tat tat cct cct act gat ggt gct cag      288
Glu Asn Thr Ala Gly Glu Tyr Tyr Tyr Pro Pro Thr Asp Gly Ala Gln
                 85                  90                  95
caa aat ata ggt tca cat att tat ttc aat act gtt agt gga tct tta      336
Gln Asn Ile Gly Ser His Ile Tyr Phe Asn Thr Val Ser Gly Ser Leu
            100                 105                 110
aca tct tca gaa act cag ata ttt aat agg cca tat ttt tta caa cgt      384
Thr Ser Ser Glu Thr Gln Ile Phe Asn Arg Pro Tyr Phe Leu Gln Arg
        115                 120                 125
gca cag ggc aca aac aac gga gtg gat cc                               413
Ala Gln Gly Thr Asn Asn Gly Val Asp
    130                 135 
           
             17 
             137 
             PRT 
             Papilloma virus 
           
            17
Gly Ser Met Glu Asp Gly Glu Met Ser Asp Thr Gly Phe Gly Ala Met
 1               5                  10                  15
Asn Phe Asp Asn Leu Cys Glu Asp Arg Ala Ser Phe Pro Leu Asp Ile
            20                  25                  30
Ile Asn Glu Thr Ser Lys Trp Pro Asp Phe Leu Lys Met Asn Lys Asp
        35                  40                  45
Pro Tyr Gly Asp His Ile Phe Phe Phe Gly Leu Arg Glu Gln Leu Tyr
    50                  55                  60
Ser Arg His His Gly Ala Arg Gly Gly Lys Met Gly Asp Thr Ile Pro
65                  70                  75                  80
Glu Asn Thr Ala Gly Glu Tyr Tyr Tyr Pro Pro Thr Asp Gly Ala Gln
                85                  90                  95
Gln Asn Ile Gly Ser His Ile Tyr Phe Asn Thr Val Ser Gly Ser Leu
            100                 105                 110
Thr Ser Ser Glu Thr Gln Ile Phe Asn Arg Pro Tyr Phe Leu Gln Arg
        115                 120                 125
Ala Gln Gly Thr Asn Asn Gly Val Asp
    130                 135 
           
             18 
             413 
             DNA 
             Papilloma virus 
           
            18
ggatccactc cgttgtttgt gccctgtgca cgttgtaaaa aatatggcct attaaatatc     60
tgagtttctg aagatgttaa agatccacta acagtattga aataaatatg tgaacctata    120
ttttgctgag caccatcagt aggaggataa taatattcgc ctgctgtatt ttctggaata    180
gtatctccca tttttcctcc ccgagcacca tgatgtctgg aatataactg ctctcgtaaa    240
ccaaagaaaa atatatgatc tccataagga tctttattca tttttagaaa atcaggccac    300
ttggaggtct catttataat gtctaaagga aatgaagctc tgtcctcgca tagattatca    360
aaattcatag caccaaaacc tgtatcactc atctcaccgt cctccatgga tcc           413 
           
             19 
             428 
             DNA 
             Papilloma virus 
             
               CDS 
               (1)...(426) 
             
           
            19
gga tcc att caa gat ggg gat atg tgc gat att ggc ttt gga gca gcc       48
Gly Ser Ile Gln Asp Gly Asp Met Cys Asp Ile Gly Phe Gly Ala Ala
 1               5                   10                  15
aat ttt aaa gca tta cag caa gat aaa tca ggt gtt cct tta gat att       96
Asn Phe Lys Ala Leu Gln Gln Asp Lys Ser Gly Val Pro Leu Asp Ile
             20                  25                  30
gtt gac agt ata tgt aaa tgg cca gat att att aaa atg gag caa gaa      144
Val Asp Ser Ile Cys Lys Trp Pro Asp Ile Ile Lys Met Glu Gln Glu
         35                  40                  45
ata tat gga gac aga tta ttt ttc ttt act aaa cgt gag caa gct tat      192
Ile Tyr Gly Asp Arg Leu Phe Phe Phe Thr Lys Arg Glu Gln Ala Tyr
     50                  55                  60
gcc agg cat tat ttc gct cgt gca gga att aat ggt gat tct tta cca      240
Ala Arg His Tyr Phe Ala Arg Ala Gly Ile Asn Gly Asp Ser Leu Pro
 65                  70                  75                  80
gat gca atg aaa cca gga gaa tat tat ctc tct cct aag ttg gga gat      288
Asp Ala Met Lys Pro Gly Glu Tyr Tyr Leu Ser Pro Lys Leu Gly Asp
                 85                  90                  95
gag caa gta ccc cag aaa gac tta gga tcg cat att tat ttt cct aca      336
Glu Gln Val Pro Gln Lys Asp Leu Gly Ser His Ile Tyr Phe Pro Thr
            100                 105                 110
gtt agt ggt tct ttg gtt tct agt gaa aat cag tta ttt aac aga cca      384
Val Ser Gly Ser Leu Val Ser Ser Glu Asn Gln Leu Phe Asn Arg Pro
        115                 120                 125
tat tgg ttg cag aaa tct cag ggc aca aac aac ggc gtg gat              426
Tyr Trp Leu Gln Lys Ser Gln Gly Thr Asn Asn Gly Val Asp
    130                 135                 140
cc                                                                   428 
           
             20 
             142 
             PRT 
             Papilloma virus 
           
            20
Gly Ser Ile Gln Asp Gly Asp Met Cys Asp Ile Gly Phe Gly Ala Ala
 1               5                  10                  15
Asn Phe Lys Ala Leu Gln Gln Asp Lys Ser Gly Val Pro Leu Asp Ile
            20                  25                  30
Val Asp Ser Ile Cys Lys Trp Pro Asp Ile Ile Lys Met Glu Gln Glu
        35                  40                  45
Ile Tyr Gly Asp Arg Leu Phe Phe Phe Thr Lys Arg Glu Gln Ala Tyr
    50                  55                  60
Ala Arg His Tyr Phe Ala Arg Ala Gly Ile Asn Gly Asp Ser Leu Pro
65                  70                  75                  80
Asp Ala Met Lys Pro Gly Glu Tyr Tyr Leu Ser Pro Lys Leu Gly Asp
                85                  90                  95
Glu Gln Val Pro Gln Lys Asp Leu Gly Ser His Ile Tyr Phe Pro Thr
            100                 105                 110
Val Ser Gly Ser Leu Val Ser Ser Glu Asn Gln Leu Phe Asn Arg Pro
        115                 120                 125
Tyr Trp Leu Gln Lys Ser Gln Gly Thr Asn Asn Gly Val Asp
    130                 135                 140 
           
             21 
             428 
             DNA 
             Papilloma virus 
           
            21
ggatccacgc cgttgtttgt gccctgagat ttctgcaacc aatatggtct gttaaataac     60
tgattttcac tagaaaccaa agaaccacta actgtaggaa aataaatatg cgatcctaag    120
tctttctggg gtacttgctc atctcccaac ttaggagaga gataatattc tcctggtttc    180
attgcatctg gtaaagaatc accattaatt cctgcacgag cgaaataatg cctggcataa    240
gcttgctcac gtttagtaaa gaaaaataat ctgtctccat atatttcttg ctccatttta    300
ataatatctg gccatttaca tatactgtca acaatatcta aaggaacacc tgatttatct    360
tgctgtaatg ctttaaaatt ggctgctcca aagccaatat cgcacatatc cccatcttga    420
atggatcc                                                             428 
           
             22 
             416 
             DNA 
             Papilloma virus 
             
               CDS 
               (1)...(414) 
             
           
            22
gga tcc ctg gaa gat ggt gaa atg gga gat att ggg ttt ggt gca gca       48
Gly Ser Leu Glu Asp Gly Glu Met Gly Asp Ile Gly Phe Gly Ala Ala
 1               5                   10                  15
aat ttt aaa acg tta caa aag gac aga gcc gga gtc agc tta gat tta       96
Asn Phe Lys Thr Leu Gln Lys Asp Arg Ala Gly Val Ser Leu Asp Leu
             20                  25                  30
gta gac act ttt agc att tgg cct gac ttt tta aaa atg act aat gat      144
Val Asp Thr Phe Ser Ile Trp Pro Asp Phe Leu Lys Met Thr Asn Asp
         35                  40                  45
att tac gga gat agt atg ttt ttc ttt gga aaa cgt gag cag ctc ttt      192
Ile Tyr Gly Asp Ser Met Phe Phe Phe Gly Lys Arg Glu Gln Leu Phe
     50                  55                  60
ggc aga cat ctt tgg aca aga gca ggt act ccc ggc gat gca att cct      240
Gly Arg His Leu Trp Thr Arg Ala Gly Thr Pro Gly Asp Ala Ile Pro
 65                  70                  75                  80
act cca gaa aat ata aac tta ata ttt cca gct gat gat ggc act agt      288
Thr Pro Glu Asn Ile Asn Leu Ile Phe Pro Ala Asp Asp Gly Thr Ser
                 85                  90                  95
caa aag gat gca ggg tct ttc act tac ttt act tca gct agt gga tct      336
Gln Lys Asp Ala Gly Ser Phe Thr Tyr Phe Thr Ser Ala Ser Gly Ser
            100                 105                 110
ctt aat act agc gat tca caa tta ttt aat aga cct tac tgg ctt cga      384
Leu Asn Thr Ser Asp Ser Gln Leu Phe Asn Arg Pro Tyr Trp Leu Arg
        115                 120                 125
cgt gca caa ggc aca aac aat ggc gtg gat cc                           416
Arg Ala Gln Gly Thr Asn Asn Gly Val Asp
    130                 135 
           
             23 
             138 
             PRT 
             Papilloma virus 
           
            23
Gly Ser Leu Glu Asp Gly Glu Met Gly Asp Ile Gly Phe Gly Ala Ala
 1               5                  10                  15
Asn Phe Lys Thr Leu Gln Lys Asp Arg Ala Gly Val Ser Leu Asp Leu
            20                  25                  30
Val Asp Thr Phe Ser Ile Trp Pro Asp Phe Leu Lys Met Thr Asn Asp
        35                  40                  45
Ile Tyr Gly Asp Ser Met Phe Phe Phe Gly Lys Arg Glu Gln Leu Phe
    50                  55                  60
Gly Arg His Leu Trp Thr Arg Ala Gly Thr Pro Gly Asp Ala Ile Pro
65                  70                  75                  80
Thr Pro Glu Asn Ile Asn Leu Ile Phe Pro Ala Asp Asp Gly Thr Ser
                85                  90                  95
Gln Lys Asp Ala Gly Ser Phe Thr Tyr Phe Thr Ser Ala Ser Gly Ser
            100                 105                 110
Leu Asn Thr Ser Asp Ser Gln Leu Phe Asn Arg Pro Tyr Trp Leu Arg
        115                 120                 125
Arg Ala Gln Gly Thr Asn Asn Gly Val Asp
    130                 135 
           
             24 
             416 
             DNA 
             Papilloma virus 
           
            24
ggatccacgc cattgtttgt gccttgtgca cgtcgaagcc agtaaggtct attaaataat     60
tgtgaatcgc tagtattaag agatccacta gctgaagtaa agtaagtgaa agaccctgca    120
tccttttgac tagtgccatc atcagctgga aatattaagt ttatattttc tggagtagga    180
attgcatcgc cgggagtacc tgctcttgtc caaagatgtc tgccaaagag ctgctcacgt    240
tttccaaaga aaaacatact atctccgtaa atatcattag tcatttttaa aaagtcaggc    300
caaatgctaa aagtgtctac taaatctaag ctgactccgg ctctgtcctt ttgtaacgtt    360
ttaaaatttg ctgcaccaaa cccaatatct cccatttcac catcttccag ggatcc        416 
           
             25 
             425 
             DNA 
             Papilloma virus 
             
               CDS 
               (1)...(423) 
             
           
            25
gga tcc cta gag gat ggg gag atg ggt gat ata gga ttt ggt gct gct       48
Gly Ser Leu Glu Asp Gly Glu Met Gly Asp Ile Gly Phe Gly Ala Ala
 1               5                   10                  15
aat ttt gct aag ctt atg caa gat aga gct ggt gta cct ctg gaa tta       96
Asn Phe Ala Lys Leu Met Gln Asp Arg Ala Gly Val Pro Leu Glu Leu
             20                  25                  30
ata gat agt att agt ata tgg cca gat ttt cta aaa atg aca aag gat      144
Ile Asp Ser Ile Ser Ile Trp Pro Asp Phe Leu Lys Met Thr Lys Asp
         35                  40                  45
att tat gga aat gaa gta ttt ttc ttt gga aaa cgc gag caa tgt tat      192
Ile Tyr Gly Asn Glu Val Phe Phe Phe Gly Lys Arg Glu Gln Cys Tyr
     50                  55                  60
gct cgc cat tta ttt gcc aga gct ggt act atg gga gaa cca gta cct      240
Ala Arg His Leu Phe Ala Arg Ala Gly Thr Met Gly Glu Pro Val Pro
 65                  70                  75                  80
aat gag act aat gga gta aat ttt ata aat gca aaa cca gga gat cca      288
Asn Glu Thr Asn Gly Val Asn Phe Ile Asn Ala Lys Pro Gly Asp Pro
                 85                  90                  95
aat ccc agg agc gct cat atg ggt tct tca gta tac ttt gca aca cct      336
Asn Pro Arg Ser Ala His Met Gly Ser Ser Val Tyr Phe Ala Thr Pro
            100                 105                 110
agt ggc tcc ctt aat acc agt gat tca caa ata ttt aac aga cct tat      384
Ser Gly Ser Leu Asn Thr Ser Asp Ser Gln Ile Phe Asn Arg Pro Tyr
        115                 120                 125
tgg tta cga cgg gct caa gga acg aac aac ggc atg gat cc               425
Trp Leu Arg Arg Ala Gln Gly Thr Asn Asn Gly Met Asp
    130                 135                 140 
           
             26 
             141 
             PRT 
             Papilloma virus 
           
            26
Gly Ser Leu Glu Asp Gly Glu Met Gly Asp Ile Gly Phe Gly Ala Ala
 1               5                  10                  15
Asn Phe Ala Lys Leu Met Gln Asp Arg Ala Gly Val Pro Leu Glu Leu
            20                  25                  30
Ile Asp Ser Ile Ser Ile Trp Pro Asp Phe Leu Lys Met Thr Lys Asp
        35                  40                  45
Ile Tyr Gly Asn Glu Val Phe Phe Phe Gly Lys Arg Glu Gln Cys Tyr
    50                  55                  60
Ala Arg His Leu Phe Ala Arg Ala Gly Thr Met Gly Glu Pro Val Pro
65                  70                  75                  80
Asn Glu Thr Asn Gly Val Asn Phe Ile Asn Ala Lys Pro Gly Asp Pro
                85                  90                  95
Asn Pro Arg Ser Ala His Met Gly Ser Ser Val Tyr Phe Ala Thr Pro
            100                 105                 110
Ser Gly Ser Leu Asn Thr Ser Asp Ser Gln Ile Phe Asn Arg Pro Tyr
        115                 120                 125
Trp Leu Arg Arg Ala Gln Gly Thr Asn Asn Gly Met Asp
    130                 135                 140 
           
             27 
             425 
             DNA 
             Papilloma virus 
           
            27
ggatccatgc cgttgttcgt tccttgagcc cgtcgtaacc aataaggtct gttaaatatt     60
tgtgaatcac tggtattaag ggagccacta ggtgttgcaa agtatactga agaacccata    120
tgagcgctcc tgggatttgg atctcctggt tttgcattta taaaatttac tccattagtc    180
tcattaggta ctggttctcc catagtacca gctctggcaa ataaatggcg agcataacat    240
tgctcgcgtt ttccaaagaa aaatacttca tttccataaa tatcctttgt catttttaga    300
aaatctggcc atatactaat actatctatt aattccagag gtacaccagc tctatcttgc    360
ataagcttag caaaattagc agcaccaaat cctatatcac ccatctcccc atcctctagg    420
gatcc                                                                425 
           
             28 
             398 
             DNA 
             Papilloma virus 
             
               CDS 
               (1)...(396) 
             
           
            28
gga tcc ctt gag gat ggg gaa atg ata gat aca ggc tat ggt gcc atg       48
Gly Ser Leu Glu Asp Gly Glu Met Ile Asp Thr Gly Tyr Gly Ala Met
 1               5                   10                  15
gac ttt cgt aca ttg cag gaa acc aaa agt gag gta cca cta gat att       96
Asp Phe Arg Thr Leu Gln Glu Thr Lys Ser Glu Val Pro Leu Asp Ile
             20                  25                  30
tgc caa tcc gtg tgt aaa tat cct gat tat ttg cag atg tct gct gat      144
Cys Gln Ser Val Cys Lys Tyr Pro Asp Tyr Leu Gln Met Ser Ala Asp
         35                  40                  45
gta tat ggg gac agt atg ttt ttt tgt ttg cgc aag gaa cag ttg ttt      192
Val Tyr Gly Asp Ser Met Phe Phe Cys Leu Arg Lys Glu Gln Leu Phe
     50                  55                  60
gcc agg cac ttt tgg aat aga ggt ggc atg gtg ggc gac aca ata cct      240
Ala Arg His Phe Trp Asn Arg Gly Gly Met Val Gly Asp Thr Ile Pro
 65                  70                  75                  80
tca gag tta tat att aaa ggc acg gat ata cgt gag cgt cct ggt act      288
Ser Glu Leu Tyr Ile Lys Gly Thr Asp Ile Arg Glu Arg Pro Gly Thr
                 85                  90                  95
cat gta tat tcc cct tcc cca agt ggc tct atg gtc tct tct gat tcc      336
His Val Tyr Ser Pro Ser Pro Ser Gly Ser Met Val Ser Ser Asp Ser
            100                 105                 110
cag ttg ttt aat aag ccc tat tgg ttg cat aag gcc caa ggc cac aat      384
Gln Leu Phe Asn Lys Pro Tyr Trp Leu His Lys Ala Gln Gly His Asn
        115                 120                 125
aac ggg atg gat cc                                                   398
Asn Gly Met Asp
    130 
           
             29 
             132 
             PRT 
             Papilloma virus 
           
            29
Gly Ser Leu Glu Asp Gly Glu Met Ile Asp Thr Gly Tyr Gly Ala Met
 1               5                  10                  15
Asp Phe Arg Thr Leu Gln Glu Thr Lys Ser Glu Val Pro Leu Asp Ile
            20                  25                  30
Cys Gln Ser Val Cys Lys Tyr Pro Asp Tyr Leu Gln Met Ser Ala Asp
        35                  40                  45
Val Tyr Gly Asp Ser Met Phe Phe Cys Leu Arg Lys Glu Gln Leu Phe
    50                  55                  60
Ala Arg His Phe Trp Asn Arg Gly Gly Met Val Gly Asp Thr Ile Pro
65                  70                  75                  80
Ser Glu Leu Tyr Ile Lys Gly Thr Asp Ile Arg Glu Arg Pro Gly Thr
                85                  90                  95
His Val Tyr Ser Pro Ser Pro Ser Gly Ser Met Val Ser Ser Asp Ser
            100                 105                 110
Gln Leu Phe Asn Lys Pro Tyr Trp Leu His Lys Ala Gln Gly His Asn
        115                 120                 125
Asn Gly Met Asp
    130 
           
             30 
             398 
             DNA 
             Papilloma virus 
           
            30
ggatccatcc cgttattgtg gccttgggcc ttatgcaacc aatagggctt attaaacaac     60
tgggaatcag aagagaccat agagccactt ggggaagggg aatatacatg agtaccagga    120
cgctcacgta tatccgtgcc tttaatatat aactctgaag gtattgtgtc gcccaccatg    180
ccacctctat tccaaaagtg cctggcaaac aactgttcct tgcgcaaaca aaaaaacata    240
ctgtccccat atacatcagc agacatctgc aaataatcag gatatttaca cacggattgg    300
caaatatcta gtggtacctc acttttggtt tcctgcaatg tacgaaagtc catggcacca    360
tagcctgtat ctatcatttc cccatcctca agggatcc                            398