Papilloma viruses, agents for detecting them and for treating diseases caused by such viruses

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

I. 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.

II. 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.

III. 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.

IV. BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the base sequence (SEQ ID NOS:1 and 3) and the amino acid sequence (SEQ ID NO:2), 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 Zelikulturen [German-type collection of micro-organisms and cell cultures]) under DSM 10104 on Jul. 11, 1995.

FIG. 2 shows the base sequence (SEQ ID NOS:4 and 6) and the amino acid sequence (SEQ ID NO:5), 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 (SEQ ID NOS:7 and 9) and the amino acid sequence (SEQ ID NO:8), 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 (SEQ ID NOS:10 and 12) and the amino acid sequence (SEQ ID NO:11), 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 (SEQ ID NOS:13 and 15) and the amino acid sequence (SEQ ID NO:14), 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 (SEQ ID NOS:16 and 18) and the amino acid sequence (SEQ ID NO:17), 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 (SEQ ID NOS:19 and 21) and the amino acid sequence (SEQ ID NO:20), 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 (SEQ ID NOS:22 and 24) and the amino acid sequence (SEQ ID NO:23), 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 (SEQ ID NOS:25 and 27) and the amino acid sequence (SEQ ID NO:26), 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 (SEQ ID NOS:28 and 30) and the amino acid sequence (SEQ ID NO:29), 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.

V. 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 HP 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. pY100 and Ycpadl 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, x1776, 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. Kimbauer 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” (p7.5 k) 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 VS 19-6-G-L1 and VSI9-6-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.

VI. EXAMPLES

A. 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 XL 1-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.

#             SEQUENCE LISTING
<160> NUMBER OF SEQ ID NOS: 30
<210> SEQ ID NO 1
<211> LENGTH: 419
<212> TYPE: DNA
<213> ORGANISM: Papilloma virus
<220> FEATURE:
<221> NAME/KEY: CDS
<222> LOCATION: (1)...(417)
<400> SEQUENCE: 1
gga tcc atg cag gat ggt gac atg tgt gat at
#a gga ttc gga gct tgc       48
Gly Ser Met Gln Asp Gly Asp Met Cys Asp Il
#e Gly Phe Gly Ala Cys
1               5
#                 10
#                 15
aat ttc agg gca ttt cag caa gat agg tca gg
#t gtt cct tta gat ata       96
Asn Phe Arg Ala Phe Gln Gln Asp Arg Ser Gl
#y Val Pro Leu Asp Ile
20
#             25
#             30
gta gat agt act tgc aag tat cca gac ttt tt
#g aaa atg aca aaa gac      144
Val Asp Ser Thr Cys Lys Tyr Pro Asp Phe Le
#u Lys Met Thr Lys Asp
35
#         40
#         45
aag tat ggt gat gaa tgc ttc ttt ttt ggt cg
#t cga gag cag ttg tat      192
Lys Tyr Gly Asp Glu Cys Phe Phe Phe Gly Ar
#g Arg Glu Gln Leu Tyr
50
#     55
#     60
gca agg cat tat ttt acc aga gca ggc aca at
#a ggt gat tct att cca      240
Ala Arg His Tyr Phe Thr Arg Ala Gly Thr Il
#e Gly Asp Ser Ile Pro
65
# 70
# 75
# 80
acg cca tat cag gaa tct gaa ttt tac aga tc
#t cca cag gat agc cag      288
Thr Pro Tyr Gln Glu Ser Glu Phe Tyr Arg Se
#r Pro Gln Asp Ser Gln
85
#                 90
#                 95
gct cag aat aat gtg gat tct cac att tat gt
#a gcc act cct agt ggt      336
Ala Gln Asn Asn Val Asp Ser His Ile Tyr Va
#l Ala Thr Pro Ser Gly
100
#           105
#           110
tct tta act agc agt gat gct cag ctg ttt aa
#c aga cct tat tgg ctc      384
Ser Leu Thr Ser Ser Asp Ala Gln Leu Phe As
#n Arg Pro Tyr Trp Leu
115
#       120
#       125
caa aat gct caa ggt acc aat aac gga atg ga
#t cc
#       419
Gln Asn Ala Gln Gly Thr Asn Asn Gly Met As
#p
130
#   135
<210> SEQ ID NO 2
<211> LENGTH: 139
<212> TYPE: PRT
<213> ORGANISM: Papilloma virus
<400> SEQUENCE: 2
Gly Ser Met Gln Asp Gly Asp Met Cys Asp Il
#e Gly Phe Gly Ala Cys
1               5
#                10
#                15
Asn Phe Arg Ala Phe Gln Gln Asp Arg Ser Gl
#y Val Pro Leu Asp Ile
20
#            25
#            30
Val Asp Ser Thr Cys Lys Tyr Pro Asp Phe Le
#u Lys Met Thr Lys Asp
35
#        40
#        45
Lys Tyr Gly Asp Glu Cys Phe Phe Phe Gly Ar
#g Arg Glu Gln Leu Tyr
50
#    55
#    60
Ala Arg His Tyr Phe Thr Arg Ala Gly Thr Il
#e Gly Asp Ser Ile Pro
65
#70
#75
#80
Thr Pro Tyr Gln Glu Ser Glu Phe Tyr Arg Se
#r Pro Gln Asp Ser Gln
85
#                90
#                95
Ala Gln Asn Asn Val Asp Ser His Ile Tyr Va
#l Ala Thr Pro Ser Gly
100
#           105
#           110
Ser Leu Thr Ser Ser Asp Ala Gln Leu Phe As
#n Arg Pro Tyr Trp Leu
115
#       120
#       125
Gln Asn Ala Gln Gly Thr Asn Asn Gly Met As
#p
130
#   135
<210> SEQ ID NO 3
<211> LENGTH: 419
<212> TYPE: DNA
<213> ORGANISM: Papilloma virus
<400> SEQUENCE: 3
ggatccattc cgttattggt accttgagca ttttggagcc aataaggtct gt
#taaacagc     60
tgagcatcac tgctagttaa agaaccacta ggagtggcta cataaatgtg ag
#aatccaca    120
ttattctgag cctggctatc ctgtggagat ctgtaaaatt cagattcctg at
#atggcgtt    180
ggaatagaat cacctattgt gcctgctctg gtaaaataat gccttgcata ca
#actgctct    240
cgacgaccaa aaaagaagca ttcatcacca tacttgtctt ttgtcatttt ca
#aaaagtct    300
ggatacttgc aagtactatc tactatatct aaaggaacac ctgacctatc tt
#gctgaaat    360
gccctgaaat tgcaagctcc gaatcctata tcacacatgt caccatcctg ca
#tggatcc     419
<210> SEQ ID NO 4
<211> LENGTH: 434
<212> TYPE: DNA
<213> ORGANISM: Papilloma virus
<220> FEATURE:
<221> NAME/KEY: CDS
<222> LOCATION: (1)...(432)
<400> SEQUENCE: 4
gga tcc atg gag gac ggt gag atg gca gac at
#a gga tat ggt aat ctt       48
Gly Ser Met Glu Asp Gly Glu Met Ala Asp Il
#e Gly Tyr Gly Asn Leu
1               5
#                 10
#                 15
aat ttt aaa gct tta cag gaa aat agg cct ga
#t gtt agt ctt gat att       96
Asn Phe Lys Ala Leu Gln Glu Asn Arg Pro As
#p Val Ser Leu Asp Ile
20
#             25
#             30
gtc aat gaa acc tgc aaa tat cca gat ttt tt
#g aag atg caa aat gat      144
Val Asn Glu Thr Cys Lys Tyr Pro Asp Phe Le
#u Lys Met Gln Asn Asp
35
#         40
#         45
gtt tat gga gac tcc tgt ttc ttt ttt gct cg
#t aga gag caa tgt tat      192
Val Tyr Gly Asp Ser Cys Phe Phe Phe Ala Ar
#g Arg Glu Gln Cys Tyr
50
#     55
#     60
gcc aga cac ttt ttt gta aga ggt ggc aac gt
#a ggg gat gac att cct      240
Ala Arg His Phe Phe Val Arg Gly Gly Asn Va
#l Gly Asp Asp Ile Pro
65
# 70
# 75
# 80
ggt gaa caa ata gac gca ggc aca tat aaa aa
#t gat ttt tac att cca      288
Gly Glu Gln Ile Asp Ala Gly Thr Tyr Lys As
#n Asp Phe Tyr Ile Pro
85
#                 90
#                 95
gga gca tca ggt cag aca caa aat aaa ata gg
#t aac tcc atg tat ttc      336
Gly Ala Ser Gly Gln Thr Gln Asn Lys Ile Gl
#y Asn Ser Met Tyr Phe
100
#           105
#           110
cca aca gtt agt ggc tca tta gtg tct agt ga
#t gct cag ctg ttt aat      384
Pro Thr Val Ser Gly Ser Leu Val Ser Ser As
#p Ala Gln Leu Phe Asn
115
#       120
#       125
agg ccc tac tgg ctc caa cgc gca cag ggc ca
#c aac aac ggc gtg gat      432
Arg Pro Tyr Trp Leu Gln Arg Ala Gln Gly Hi
#s Asn Asn Gly Val Asp
130
#   135
#   140
cc
#
#
#             434
<210> SEQ ID NO 5
<211> LENGTH: 144
<212> TYPE: PRT
<213> ORGANISM: Papilloma virus
<400> SEQUENCE: 5
Gly Ser Met Glu Asp Gly Glu Met Ala Asp Il
#e Gly Tyr Gly Asn Leu
1               5
#                10
#                15
Asn Phe Lys Ala Leu Gln Glu Asn Arg Pro As
#p Val Ser Leu Asp Ile
20
#            25
#            30
Val Asn Glu Thr Cys Lys Tyr Pro Asp Phe Le
#u Lys Met Gln Asn Asp
35
#        40
#        45
Val Tyr Gly Asp Ser Cys Phe Phe Phe Ala Ar
#g Arg Glu Gln Cys Tyr
50
#    55
#    60
Ala Arg His Phe Phe Val Arg Gly Gly Asn Va
#l Gly Asp Asp Ile Pro
65
#70
#75
#80
Gly Glu Gln Ile Asp Ala Gly Thr Tyr Lys As
#n Asp Phe Tyr Ile Pro
85
#                90
#                95
Gly Ala Ser Gly Gln Thr Gln Asn Lys Ile Gl
#y Asn Ser Met Tyr Phe
100
#           105
#           110
Pro Thr Val Ser Gly Ser Leu Val Ser Ser As
#p Ala Gln Leu Phe Asn
115
#       120
#       125
Arg Pro Tyr Trp Leu Gln Arg Ala Gln Gly Hi
#s Asn Asn Gly Val Asp
130
#   135
#   140
<210> SEQ ID NO 6
<211> LENGTH: 434
<212> TYPE: DNA
<213> ORGANISM: Papilloma virus
<400> SEQUENCE: 6
ggatccacgc cgttgttgtg gccctgtgcg cgttggagcc agtagggcct at
#taaacagc     60
tgagcatcac tagacactaa tgagccacta actgttggga aatacatgga gt
#tacctatt    120
ttattttgtg tctgacctga tgctcctgga atgtaaaaat catttttata tg
#tgcctgcg    180
tctatttgtt caccaggaat gtcatcccct acgttgccac ctcttacaaa aa
#agtgtctg    240
gcataacatt gctctctacg agcaaaaaag aaacaggagt ctccataaac at
#cattttgc    300
atcttcaaaa aatctggata tttgcaggtt tcattgacaa tatcaagact aa
#catcaggc    360
ctattttcct gtaaagcttt aaaattaaga ttaccatatc ctatgtctgc ca
#tctcaccg    420
tcctccatgg atcc
#
#
#    434
<210> SEQ ID NO 7
<211> LENGTH: 410
<212> TYPE: DNA
<213> ORGANISM: Papilloma virus
<220> FEATURE:
<221> NAME/KEY: CDS
<222> LOCATION: (1)...(408)
<400> SEQUENCE: 7
gga tcc cta gag gat ggt gat atg ggt gat at
#a gga ttt ggg cat gct       48
Gly Ser Leu Glu Asp Gly Asp Met Gly Asp Il
#e Gly Phe Gly His Ala
1               5
#                 10
#                 15
aat ttt agc cgt tta caa gaa gat aaa gca gg
#t gtg cca tta gaa tta       96
Asn Phe Ser Arg Leu Gln Glu Asp Lys Ala Gl
#y Val Pro Leu Glu Leu
20
#             25
#             30
gtg gac act ttt agt ata tgg cct gac ttt tt
#a cgc atg acc agt gat      144
Val Asp Thr Phe Ser Ile Trp Pro Asp Phe Le
#u Arg Met Thr Ser Asp
35
#         40
#         45
ata tat gga gat gct gtg ttt ttt tgg gga aa
#g cga gaa cat atg ttt      192
Ile Tyr Gly Asp Ala Val Phe Phe Trp Gly Ly
#s Arg Glu His Met Phe
50
#     55
#     60
gcc aga cat tta tgg gca aga gct gga act at
#g ggc gac gct att cca      240
Ala Arg His Leu Trp Ala Arg Ala Gly Thr Me
#t Gly Asp Ala Ile Pro
65
# 70
# 75
# 80
gat aat aat gca gag ttt ttt ctg cat ccc aa
#t ggt gca cct caa aat      288
Asp Asn Asn Ala Glu Phe Phe Leu His Pro As
#n Gly Ala Pro Gln Asn
85
#                 90
#                 95
aag tta gcc tca ttt gct tat ttt cca aca cc
#t agt ggt tct ctt aat      336
Lys Leu Ala Ser Phe Ala Tyr Phe Pro Thr Pr
#o Ser Gly Ser Leu Asn
100
#           105
#           110
acc agt gat aat caa ttg ttt aat aag ccg ta
#t tgg ttg cga aaa gct      384
Thr Ser Asp Asn Gln Leu Phe Asn Lys Pro Ty
#r 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
<210> SEQ ID NO 8
<211> LENGTH: 136
<212> TYPE: PRT
<213> ORGANISM: Papilloma virus
<400> SEQUENCE: 8
Gly Ser Leu Glu Asp Gly Asp Met Gly Asp Il
#e Gly Phe Gly His Ala
1               5
#                10
#                15
Asn Phe Ser Arg Leu Gln Glu Asp Lys Ala Gl
#y Val Pro Leu Glu Leu
20
#            25
#            30
Val Asp Thr Phe Ser Ile Trp Pro Asp Phe Le
#u Arg Met Thr Ser Asp
35
#        40
#        45
Ile Tyr Gly Asp Ala Val Phe Phe Trp Gly Ly
#s Arg Glu His Met Phe
50
#    55
#    60
Ala Arg His Leu Trp Ala Arg Ala Gly Thr Me
#t Gly Asp Ala Ile Pro
65
#70
#75
#80
Asp Asn Asn Ala Glu Phe Phe Leu His Pro As
#n Gly Ala Pro Gln Asn
85
#                90
#                95
Lys Leu Ala Ser Phe Ala Tyr Phe Pro Thr Pr
#o Ser Gly Ser Leu Asn
100
#           105
#           110
Thr Ser Asp Asn Gln Leu Phe Asn Lys Pro Ty
#r Trp Leu Arg Lys Ala
115
#       120
#       125
Gln Gly Thr Asn Asn Gly Met Asp
130
#   135
<210> SEQ ID NO 9
<211> LENGTH: 410
<212> TYPE: DNA
<213> ORGANISM: Papilloma virus
<400> SEQUENCE: 9
ggatccatcc cattgttggt gccctgagct tttcgcaacc aatacggctt at
#taaacaat     60
tgattatcac tggtattaag agaaccacta ggtgttggaa aataagcaaa tg
#aggctaac    120
ttattttgag gtgcaccatt gggatgcaga aaaaactctg cattattatc tg
#gaatagcg    180
tcgcccatag ttccagctct tgcccataaa tgtctggcaa acatatgttc tc
#gctttccc    240
caaaaaaaca cagcatctcc atatatatca ctggtcatgc gtaaaaagtc ag
#gccatata    300
ctaaaagtgt ccactaattc taatggcaca cctgctttat cttcttgtaa ac
#ggctaaaa    360
ttagcatgcc caaatcctat atcacccata tcaccatcct ctagggatcc
#             410
<210> SEQ ID NO 10
<211> LENGTH: 437
<212> TYPE: DNA
<213> ORGANISM: Papilloma virus
<220> FEATURE:
<221> NAME/KEY: CDS
<222> LOCATION: (1)...(435)
<400> SEQUENCE: 10
gga tcc att gag gat gcg gat atg agt gat at
#a gga ttt gga gct gtg       48
Gly Ser Ile Glu Asp Ala Asp Met Ser Asp Il
#e Gly Phe Gly Ala Val
1               5
#                 10
#                 15
aat ttt agc act ttc tct gaa agc cgg gct ga
#t gca cct tta gaa tta       96
Asn Phe Ser Thr Phe Ser Glu Ser Arg Ala As
#p Ala Pro Leu Glu Leu
20
#             25
#             30
atc aat tct att agt aaa tgg cct gat ttt at
#t caa atg tct aag gat      144
Ile Asn Ser Ile Ser Lys Trp Pro Asp Phe Il
#e Gln Met Ser Lys Asp
35
#         40
#         45
att tat ggc gat aga atg ttt ttc ttt gga aa
#a cgt gag cag atg tat      192
Ile Tyr Gly Asp Arg Met Phe Phe Phe Gly Ly
#s Arg Glu Gln Met Tyr
50
#     55
#     60
gca aga cac aca ttt tgt aaa gat ggt gct gt
#g gga gat gct att cca      240
Ala Arg His Thr Phe Cys Lys Asp Gly Ala Va
#l Gly Asp Ala Ile Pro
65
# 70
# 75
# 80
gaa aat tta aat aat gat gag gat gtt cat ca
#t agg ttt tta tta aat      288
Glu Asn Leu Asn Asn Asp Glu Asp Val His Hi
#s Arg Phe Leu Leu Asn
85
#                 90
#                 95
cct aag cct gac gca cca cca tat tca aac tt
#a gga aac agt act tac      336
Pro Lys Pro Asp Ala Pro Pro Tyr Ser Asn Le
#u Gly Asn Ser Thr Tyr
100
#           105
#           110
ttt cct atg cca agt ggt tca tta gtt agt ag
#t gaa act caa tta ttt      384
Phe Pro Met Pro Ser Gly Ser Leu Val Ser Se
#r Glu Thr Gln Leu Phe
115
#       120
#       125
aac aga cca ttt tgg cta cat cga gca cag gg
#c acc aat aac ggc atg      432
Asn Arg Pro Phe Trp Leu His Arg Ala Gln Gl
#y Thr Asn Asn Gly Met
130
#   135
#   140
gat cc
#
#
#           437
Asp
145
<210> SEQ ID NO 11
<211> LENGTH: 145
<212> TYPE: PRT
<213> ORGANISM: Papilloma virus
<400> SEQUENCE: 11
Gly Ser Ile Glu Asp Ala Asp Met Ser Asp Il
#e Gly Phe Gly Ala Val
1               5
#                10
#                15
Asn Phe Ser Thr Phe Ser Glu Ser Arg Ala As
#p Ala Pro Leu Glu Leu
20
#            25
#            30
Ile Asn Ser Ile Ser Lys Trp Pro Asp Phe Il
#e Gln Met Ser Lys Asp
35
#        40
#        45
Ile Tyr Gly Asp Arg Met Phe Phe Phe Gly Ly
#s Arg Glu Gln Met Tyr
50
#    55
#    60
Ala Arg His Thr Phe Cys Lys Asp Gly Ala Va
#l Gly Asp Ala Ile Pro
65
#70
#75
#80
Glu Asn Leu Asn Asn Asp Glu Asp Val His Hi
#s Arg Phe Leu Leu Asn
85
#                90
#                95
Pro Lys Pro Asp Ala Pro Pro Tyr Ser Asn Le
#u Gly Asn Ser Thr Tyr
100
#           105
#           110
Phe Pro Met Pro Ser Gly Ser Leu Val Ser Se
#r Glu Thr Gln Leu Phe
115
#       120
#       125
Asn Arg Pro Phe Trp Leu His Arg Ala Gln Gl
#y Thr Asn Asn Gly Met
130
#   135
#   140
Asp
145
<210> SEQ ID NO 12
<211> LENGTH: 437
<212> TYPE: DNA
<213> ORGANISM: Papilloma virus
<400> SEQUENCE: 12
ggatccatgc cgttattggt gccctgtgct cgatgtagcc aaaatggtct gt
#taaataat     60
tgagtttcac tactaactaa tgaaccactt ggcataggaa agtaagtact gt
#ttcctaag    120
tttgaatatg gtggtgcgtc aggcttagga tttaataaaa acctatgatg aa
#catcctca    180
tcattattta aattttctgg aatagcatct cccacagcac catctttaca aa
#atgtgtgt    240
cttgcataca tctgctcacg ttttccaaag aaaaacattc tatcgccata aa
#tatcctta    300
gacatttgaa taaaatcagg ccatttacta atagaattga ttaattctaa ag
#gtgcatca    360
gcccggcttt cagagaaagt gctaaaattc acagctccaa atcctatatc ac
#tcatatcc    420
gcatcctcaa tggatcc
#
#
#  437
<210> SEQ ID NO 13
<211> LENGTH: 416
<212> TYPE: DNA
<213> ORGANISM: Papilloma virus
<220> FEATURE:
<221> NAME/KEY: CDS
<222> LOCATION: (1)...(414)
<400> SEQUENCE: 13
gga tcc atg gag gat ggt gaa atg ggc gac at
#a ggc ttt gga gcc ttt       48
Gly Ser Met Glu Asp Gly Glu Met Gly Asp Il
#e Gly Phe Gly Ala Phe
1               5
#                 10
#                 15
aat ttt aaa gcc cta cag aaa gat cgt gct gg
#t gtt agt tta gat tta       96
Asn Phe Lys Ala Leu Gln Lys Asp Arg Ala Gl
#y Val Ser Leu Asp Leu
20
#             25
#             30
gtt gat aca ttc agt ata tgg cca gac ttt tt
#a aaa atg act aat gat      144
Val Asp Thr Phe Ser Ile Trp Pro Asp Phe Le
#u Lys Met Thr Asn Asp
35
#         40
#         45
ata tat ggt gac agt atc ttt ttt tat ggt aa
#a aga gaa cag cta ttt      192
Ile Tyr Gly Asp Ser Ile Phe Phe Tyr Gly Ly
#s Arg Glu Gln Leu Phe
50
#     55
#     60
agt aga cac ttg tgg gcc cgc gca gga acg gc
#t gga gat gcc att cca      240
Ser Arg His Leu Trp Ala Arg Ala Gly Thr Al
#a Gly Asp Ala Ile Pro
65
# 70
# 75
# 80
tct cct gat aac aaa aat cta ata ttt cag gg
#t gat gat gca gtg cca      288
Ser Pro Asp Asn Lys Asn Leu Ile Phe Gln Gl
#y Asp Asp Ala Val Pro
85
#                 90
#                 95
caa aag act gct ggg tct ttt act tat ttt ag
#t gcc cct agt ggg tca      336
Gln Lys Thr Ala Gly Ser Phe Thr Tyr Phe Se
#r Ala Pro Ser Gly Ser
100
#           105
#           110
tta aca act agt gat tct cag tta ttt aat ag
#g cca tat tgg tta aga      384
Leu Thr Thr Ser Asp Ser Gln Leu Phe Asn Ar
#g 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
<210> SEQ ID NO 14
<211> LENGTH: 138
<212> TYPE: PRT
<213> ORGANISM: Papilloma virus
<400> SEQUENCE: 14
Gly Ser Met Glu Asp Gly Glu Met Gly Asp Il
#e Gly Phe Gly Ala Phe
1               5
#                10
#                15
Asn Phe Lys Ala Leu Gln Lys Asp Arg Ala Gl
#y Val Ser Leu Asp Leu
20
#            25
#            30
Val Asp Thr Phe Ser Ile Trp Pro Asp Phe Le
#u Lys Met Thr Asn Asp
35
#        40
#        45
Ile Tyr Gly Asp Ser Ile Phe Phe Tyr Gly Ly
#s Arg Glu Gln Leu Phe
50
#    55
#    60
Ser Arg His Leu Trp Ala Arg Ala Gly Thr Al
#a Gly Asp Ala Ile Pro
65
#70
#75
#80
Ser Pro Asp Asn Lys Asn Leu Ile Phe Gln Gl
#y Asp Asp Ala Val Pro
85
#                90
#                95
Gln Lys Thr Ala Gly Ser Phe Thr Tyr Phe Se
#r Ala Pro Ser Gly Ser
100
#           105
#           110
Leu Thr Thr Ser Asp Ser Gln Leu Phe Asn Ar
#g Pro Tyr Trp Leu Arg
115
#       120
#       125
Arg Ala Gln Gly Thr Asn Asn Gly Val Asp
130
#   135
<210> SEQ ID NO 15
<211> LENGTH: 416
<212> TYPE: DNA
<213> ORGANISM: Papilloma virus
<400> SEQUENCE: 15
ggatccacac cgttgttggt accttgagct cttcttaacc aatatggcct at
#taaataac     60
tgagaatcac tagttgttaa tgacccacta ggggcactaa aataagtaaa ag
#acccagca    120
gtcttttgtg gcactgcatc atcaccctga aatattagat ttttgttatc ag
#gagatgga    180
atggcatctc cagccgttcc tgcgcgggcc cacaagtgtc tactaaatag ct
#gttctctt    240
ttaccataaa aaaagatact gtcaccatat atatcattag tcatttttaa aa
#agtctggc    300
catatactga atgtatcaac taaatctaaa ctaacaccag cacgatcttt ct
#gtagggct    360
ttaaaattaa aggctccaaa gcctatgtcg cccatttcac catcctccat gg
#atcc        416
<210> SEQ ID NO 16
<211> LENGTH: 413
<212> TYPE: DNA
<213> ORGANISM: Papilloma virus
<220> FEATURE:
<221> NAME/KEY: CDS
<222> LOCATION: (1)...(411)
<400> SEQUENCE: 16
gga tcc atg gag gac ggt gag atg agt gat ac
#a ggt ttt ggt gct atg       48
Gly Ser Met Glu Asp Gly Glu Met Ser Asp Th
#r Gly Phe Gly Ala Met
1               5
#                 10
#                 15
aat ttt gat aat cta tgc gag gac aga gct tc
#a ttt cct tta gac att       96
Asn Phe Asp Asn Leu Cys Glu Asp Arg Ala Se
#r Phe Pro Leu Asp Ile
20
#             25
#             30
ata aat gag acc tcc aag tgg cct gat ttt ct
#a aaa atg aat aaa gat      144
Ile Asn Glu Thr Ser Lys Trp Pro Asp Phe Le
#u Lys Met Asn Lys Asp
35
#         40
#         45
cct tat gga gat cat ata ttt ttc ttt ggt tt
#a cga gag cag tta tat      192
Pro Tyr Gly Asp His Ile Phe Phe Phe Gly Le
#u Arg Glu Gln Leu Tyr
50
#     55
#     60
tcc aga cat cat ggt gct cgg gga gga aaa at
#g gga gat act att cca      240
Ser Arg His His Gly Ala Arg Gly Gly Lys Me
#t Gly Asp Thr Ile Pro
65
# 70
# 75
# 80
gaa aat aca gca ggc gaa tat tat tat cct cc
#t act gat ggt gct cag      288
Glu Asn Thr Ala Gly Glu Tyr Tyr Tyr Pro Pr
#o Thr Asp Gly Ala Gln
85
#                 90
#                 95
caa aat ata ggt tca cat att tat ttc aat ac
#t gtt agt gga tct tta      336
Gln Asn Ile Gly Ser His Ile Tyr Phe Asn Th
#r Val Ser Gly Ser Leu
100
#           105
#           110
aca tct tca gaa act cag ata ttt aat agg cc
#a tat ttt tta caa cgt      384
Thr Ser Ser Glu Thr Gln Ile Phe Asn Arg Pr
#o 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
<210> SEQ ID NO 17
<211> LENGTH: 137
<212> TYPE: PRT
<213> ORGANISM: Papilloma virus
<400> SEQUENCE: 17
Gly Ser Met Glu Asp Gly Glu Met Ser Asp Th
#r Gly Phe Gly Ala Met
1               5
#                10
#                15
Asn Phe Asp Asn Leu Cys Glu Asp Arg Ala Se
#r Phe Pro Leu Asp Ile
20
#            25
#            30
Ile Asn Glu Thr Ser Lys Trp Pro Asp Phe Le
#u Lys Met Asn Lys Asp
35
#        40
#        45
Pro Tyr Gly Asp His Ile Phe Phe Phe Gly Le
#u Arg Glu Gln Leu Tyr
50
#    55
#    60
Ser Arg His His Gly Ala Arg Gly Gly Lys Me
#t Gly Asp Thr Ile Pro
65
#70
#75
#80
Glu Asn Thr Ala Gly Glu Tyr Tyr Tyr Pro Pr
#o Thr Asp Gly Ala Gln
85
#                90
#                95
Gln Asn Ile Gly Ser His Ile Tyr Phe Asn Th
#r Val Ser Gly Ser Leu
100
#           105
#           110
Thr Ser Ser Glu Thr Gln Ile Phe Asn Arg Pr
#o Tyr Phe Leu Gln Arg
115
#       120
#       125
Ala Gln Gly Thr Asn Asn Gly Val Asp
130
#   135
<210> SEQ ID NO 18
<211> LENGTH: 413
<212> TYPE: DNA
<213> ORGANISM: Papilloma virus
<400> SEQUENCE: 18
ggatccactc cgttgtttgt gccctgtgca cgttgtaaaa aatatggcct at
#taaatatc     60
tgagtttctg aagatgttaa agatccacta acagtattga aataaatatg tg
#aacctata    120
ttttgctgag caccatcagt aggaggataa taatattcgc ctgctgtatt tt
#ctggaata    180
gtatctccca tttttcctcc ccgagcacca tgatgtctgg aatataactg ct
#ctcgtaaa    240
ccaaagaaaa atatatgatc tccataagga tctttattca tttttagaaa at
#caggccac    300
ttggaggtct catttataat gtctaaagga aatgaagctc tgtcctcgca ta
#gattatca    360
aaattcatag caccaaaacc tgtatcactc atctcaccgt cctccatgga tc
#c           413
<210> SEQ ID NO 19
<211> LENGTH: 428
<212> TYPE: DNA
<213> ORGANISM: Papilloma virus
<220> FEATURE:
<221> NAME/KEY: CDS
<222> LOCATION: (1)...(426)
<400> SEQUENCE: 19
gga tcc att caa gat ggg gat atg tgc gat at
#t ggc ttt gga gca gcc       48
Gly Ser Ile Gln Asp Gly Asp Met Cys Asp Il
#e Gly Phe Gly Ala Ala
1               5
#                 10
#                 15
aat ttt aaa gca tta cag caa gat aaa tca gg
#t gtt cct tta gat att       96
Asn Phe Lys Ala Leu Gln Gln Asp Lys Ser Gl
#y Val Pro Leu Asp Ile
20
#             25
#             30
gtt gac agt ata tgt aaa tgg cca gat att at
#t aaa atg gag caa gaa      144
Val Asp Ser Ile Cys Lys Trp Pro Asp Ile Il
#e Lys Met Glu Gln Glu
35
#         40
#         45
ata tat gga gac aga tta ttt ttc ttt act aa
#a cgt gag caa gct tat      192
Ile Tyr Gly Asp Arg Leu Phe Phe Phe Thr Ly
#s Arg Glu Gln Ala Tyr
50
#     55
#     60
gcc agg cat tat ttc gct cgt gca gga att aa
#t ggt gat tct tta cca      240
Ala Arg His Tyr Phe Ala Arg Ala Gly Ile As
#n Gly Asp Ser Leu Pro
65
# 70
# 75
# 80
gat gca atg aaa cca gga gaa tat tat ctc tc
#t cct aag ttg gga gat      288
Asp Ala Met Lys Pro Gly Glu Tyr Tyr Leu Se
#r Pro Lys Leu Gly Asp
85
#                 90
#                 95
gag caa gta ccc cag aaa gac tta gga tcg ca
#t att tat ttt cct aca      336
Glu Gln Val Pro Gln Lys Asp Leu Gly Ser Hi
#s Ile Tyr Phe Pro Thr
100
#           105
#           110
gtt agt ggt tct ttg gtt tct agt gaa aat ca
#g tta ttt aac aga cca      384
Val Ser Gly Ser Leu Val Ser Ser Glu Asn Gl
#n Leu Phe Asn Arg Pro
115
#       120
#       125
tat tgg ttg cag aaa tct cag ggc aca aac aa
#c ggc gtg gat
# 426
Tyr Trp Leu Gln Lys Ser Gln Gly Thr Asn As
#n Gly Val Asp
130
#   135
#   140
cc
#
#
#             428
<210> SEQ ID NO 20
<211> LENGTH: 142
<212> TYPE: PRT
<213> ORGANISM: Papilloma virus
<400> SEQUENCE: 20
Gly Ser Ile Gln Asp Gly Asp Met Cys Asp Il
#e Gly Phe Gly Ala Ala
1               5
#                10
#                15
Asn Phe Lys Ala Leu Gln Gln Asp Lys Ser Gl
#y Val Pro Leu Asp Ile
20
#            25
#            30
Val Asp Ser Ile Cys Lys Trp Pro Asp Ile Il
#e Lys Met Glu Gln Glu
35
#        40
#        45
Ile Tyr Gly Asp Arg Leu Phe Phe Phe Thr Ly
#s Arg Glu Gln Ala Tyr
50
#    55
#    60
Ala Arg His Tyr Phe Ala Arg Ala Gly Ile As
#n Gly Asp Ser Leu Pro
65
#70
#75
#80
Asp Ala Met Lys Pro Gly Glu Tyr Tyr Leu Se
#r Pro Lys Leu Gly Asp
85
#                90
#                95
Glu Gln Val Pro Gln Lys Asp Leu Gly Ser Hi
#s Ile Tyr Phe Pro Thr
100
#           105
#           110
Val Ser Gly Ser Leu Val Ser Ser Glu Asn Gl
#n Leu Phe Asn Arg Pro
115
#       120
#       125
Tyr Trp Leu Gln Lys Ser Gln Gly Thr Asn As
#n Gly Val Asp
130
#   135
#   140
<210> SEQ ID NO 21
<211> LENGTH: 428
<212> TYPE: DNA
<213> ORGANISM: Papilloma virus
<400> SEQUENCE: 21
ggatccacgc cgttgtttgt gccctgagat ttctgcaacc aatatggtct gt
#taaataac     60
tgattttcac tagaaaccaa agaaccacta actgtaggaa aataaatatg cg
#atcctaag    120
tctttctggg gtacttgctc atctcccaac ttaggagaga gataatattc tc
#ctggtttc    180
attgcatctg gtaaagaatc accattaatt cctgcacgag cgaaataatg cc
#tggcataa    240
gcttgctcac gtttagtaaa gaaaaataat ctgtctccat atatttcttg ct
#ccatttta    300
ataatatctg gccatttaca tatactgtca acaatatcta aaggaacacc tg
#atttatct    360
tgctgtaatg ctttaaaatt ggctgctcca aagccaatat cgcacatatc cc
#catcttga    420
atggatcc
#
#
#         428
<210> SEQ ID NO 22
<211> LENGTH: 416
<212> TYPE: DNA
<213> ORGANISM: Papilloma virus
<220> FEATURE:
<221> NAME/KEY: CDS
<222> LOCATION: (1)...(414)
<400> SEQUENCE: 22
gga tcc ctg gaa gat ggt gaa atg gga gat at
#t ggg ttt ggt gca gca       48
Gly Ser Leu Glu Asp Gly Glu Met Gly Asp Il
#e Gly Phe Gly Ala Ala
1               5
#                 10
#                 15
aat ttt aaa acg tta caa aag gac aga gcc gg
#a gtc agc tta gat tta       96
Asn Phe Lys Thr Leu Gln Lys Asp Arg Ala Gl
#y Val Ser Leu Asp Leu
20
#             25
#             30
gta gac act ttt agc att tgg cct gac ttt tt
#a aaa atg act aat gat      144
Val Asp Thr Phe Ser Ile Trp Pro Asp Phe Le
#u Lys Met Thr Asn Asp
35
#         40
#         45
att tac gga gat agt atg ttt ttc ttt gga aa
#a cgt gag cag ctc ttt      192
Ile Tyr Gly Asp Ser Met Phe Phe Phe Gly Ly
#s Arg Glu Gln Leu Phe
50
#     55
#     60
ggc aga cat ctt tgg aca aga gca ggt act cc
#c ggc gat gca att cct      240
Gly Arg His Leu Trp Thr Arg Ala Gly Thr Pr
#o Gly Asp Ala Ile Pro
65
# 70
# 75
# 80
act cca gaa aat ata aac tta ata ttt cca gc
#t gat gat ggc act agt      288
Thr Pro Glu Asn Ile Asn Leu Ile Phe Pro Al
#a Asp Asp Gly Thr Ser
85
#                 90
#                 95
caa aag gat gca ggg tct ttc act tac ttt ac
#t tca gct agt gga tct      336
Gln Lys Asp Ala Gly Ser Phe Thr Tyr Phe Th
#r Ser Ala Ser Gly Ser
100
#           105
#           110
ctt aat act agc gat tca caa tta ttt aat ag
#a cct tac tgg ctt cga      384
Leu Asn Thr Ser Asp Ser Gln Leu Phe Asn Ar
#g 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
<210> SEQ ID NO 23
<211> LENGTH: 138
<212> TYPE: PRT
<213> ORGANISM: Papilloma virus
<400> SEQUENCE: 23
Gly Ser Leu Glu Asp Gly Glu Met Gly Asp Il
#e Gly Phe Gly Ala Ala
1               5
#                10
#                15
Asn Phe Lys Thr Leu Gln Lys Asp Arg Ala Gl
#y Val Ser Leu Asp Leu
20
#            25
#            30
Val Asp Thr Phe Ser Ile Trp Pro Asp Phe Le
#u Lys Met Thr Asn Asp
35
#        40
#        45
Ile Tyr Gly Asp Ser Met Phe Phe Phe Gly Ly
#s Arg Glu Gln Leu Phe
50
#    55
#    60
Gly Arg His Leu Trp Thr Arg Ala Gly Thr Pr
#o Gly Asp Ala Ile Pro
65
#70
#75
#80
Thr Pro Glu Asn Ile Asn Leu Ile Phe Pro Al
#a Asp Asp Gly Thr Ser
85
#                90
#                95
Gln Lys Asp Ala Gly Ser Phe Thr Tyr Phe Th
#r Ser Ala Ser Gly Ser
100
#           105
#           110
Leu Asn Thr Ser Asp Ser Gln Leu Phe Asn Ar
#g Pro Tyr Trp Leu Arg
115
#       120
#       125
Arg Ala Gln Gly Thr Asn Asn Gly Val Asp
130
#   135
<210> SEQ ID NO 24
<211> LENGTH: 416
<212> TYPE: DNA
<213> ORGANISM: Papilloma virus
<400> SEQUENCE: 24
ggatccacgc cattgtttgt gccttgtgca cgtcgaagcc agtaaggtct at
#taaataat     60
tgtgaatcgc tagtattaag agatccacta gctgaagtaa agtaagtgaa ag
#accctgca    120
tccttttgac tagtgccatc atcagctgga aatattaagt ttatattttc tg
#gagtagga    180
attgcatcgc cgggagtacc tgctcttgtc caaagatgtc tgccaaagag ct
#gctcacgt    240
tttccaaaga aaaacatact atctccgtaa atatcattag tcatttttaa aa
#agtcaggc    300
caaatgctaa aagtgtctac taaatctaag ctgactccgg ctctgtcctt tt
#gtaacgtt    360
ttaaaatttg ctgcaccaaa cccaatatct cccatttcac catcttccag gg
#atcc        416
<210> SEQ ID NO 25
<211> LENGTH: 425
<212> TYPE: DNA
<213> ORGANISM: Papilloma virus
<220> FEATURE:
<221> NAME/KEY: CDS
<222> LOCATION: (1)...(423)
<400> SEQUENCE: 25
gga tcc cta gag gat ggg gag atg ggt gat at
#a gga ttt ggt gct gct       48
Gly Ser Leu Glu Asp Gly Glu Met Gly Asp Il
#e Gly Phe Gly Ala Ala
1               5
#                 10
#                 15
aat ttt gct aag ctt atg caa gat aga gct gg
#t gta cct ctg gaa tta       96
Asn Phe Ala Lys Leu Met Gln Asp Arg Ala Gl
#y Val Pro Leu Glu Leu
20
#             25
#             30
ata gat agt att agt ata tgg cca gat ttt ct
#a aaa atg aca aag gat      144
Ile Asp Ser Ile Ser Ile Trp Pro Asp Phe Le
#u Lys Met Thr Lys Asp
35
#         40
#         45
att tat gga aat gaa gta ttt ttc ttt gga aa
#a cgc gag caa tgt tat      192
Ile Tyr Gly Asn Glu Val Phe Phe Phe Gly Ly
#s Arg Glu Gln Cys Tyr
50
#     55
#     60
gct cgc cat tta ttt gcc aga gct ggt act at
#g gga gaa cca gta cct      240
Ala Arg His Leu Phe Ala Arg Ala Gly Thr Me
#t Gly Glu Pro Val Pro
65
# 70
# 75
# 80
aat gag act aat gga gta aat ttt ata aat gc
#a aaa cca gga gat cca      288
Asn Glu Thr Asn Gly Val Asn Phe Ile Asn Al
#a Lys Pro Gly Asp Pro
85
#                 90
#                 95
aat ccc agg agc gct cat atg ggt tct tca gt
#a tac ttt gca aca cct      336
Asn Pro Arg Ser Ala His Met Gly Ser Ser Va
#l Tyr Phe Ala Thr Pro
100
#           105
#           110
agt ggc tcc ctt aat acc agt gat tca caa at
#a ttt aac aga cct tat      384
Ser Gly Ser Leu Asn Thr Ser Asp Ser Gln Il
#e Phe Asn Arg Pro Tyr
115
#       120
#       125
tgg tta cga cgg gct caa gga acg aac aac gg
#c atg gat cc
#  425
Trp Leu Arg Arg Ala Gln Gly Thr Asn Asn Gl
#y Met Asp
130
#   135
#   140
<210> SEQ ID NO 26
<211> LENGTH: 141
<212> TYPE: PRT
<213> ORGANISM: Papilloma virus
<400> SEQUENCE: 26
Gly Ser Leu Glu Asp Gly Glu Met Gly Asp Il
#e Gly Phe Gly Ala Ala
1               5
#                10
#                15
Asn Phe Ala Lys Leu Met Gln Asp Arg Ala Gl
#y Val Pro Leu Glu Leu
20
#            25
#            30
Ile Asp Ser Ile Ser Ile Trp Pro Asp Phe Le
#u Lys Met Thr Lys Asp
35
#        40
#        45
Ile Tyr Gly Asn Glu Val Phe Phe Phe Gly Ly
#s Arg Glu Gln Cys Tyr
50
#    55
#    60
Ala Arg His Leu Phe Ala Arg Ala Gly Thr Me
#t Gly Glu Pro Val Pro
65
#70
#75
#80
Asn Glu Thr Asn Gly Val Asn Phe Ile Asn Al
#a Lys Pro Gly Asp Pro
85
#                90
#                95
Asn Pro Arg Ser Ala His Met Gly Ser Ser Va
#l Tyr Phe Ala Thr Pro
100
#           105
#           110
Ser Gly Ser Leu Asn Thr Ser Asp Ser Gln Il
#e Phe Asn Arg Pro Tyr
115
#       120
#       125
Trp Leu Arg Arg Ala Gln Gly Thr Asn Asn Gl
#y Met Asp
130
#   135
#   140
<210> SEQ ID NO 27
<211> LENGTH: 425
<212> TYPE: DNA
<213> ORGANISM: Papilloma virus
<400> SEQUENCE: 27
ggatccatgc cgttgttcgt tccttgagcc cgtcgtaacc aataaggtct gt
#taaatatt     60
tgtgaatcac tggtattaag ggagccacta ggtgttgcaa agtatactga ag
#aacccata    120
tgagcgctcc tgggatttgg atctcctggt tttgcattta taaaatttac tc
#cattagtc    180
tcattaggta ctggttctcc catagtacca gctctggcaa ataaatggcg ag
#cataacat    240
tgctcgcgtt ttccaaagaa aaatacttca tttccataaa tatcctttgt ca
#tttttaga    300
aaatctggcc atatactaat actatctatt aattccagag gtacaccagc tc
#tatcttgc    360
ataagcttag caaaattagc agcaccaaat cctatatcac ccatctcccc at
#cctctagg    420
gatcc
#
#
#           425
<210> SEQ ID NO 28
<211> LENGTH: 398
<212> TYPE: DNA
<213> ORGANISM: Papilloma virus
<220> FEATURE:
<221> NAME/KEY: CDS
<222> LOCATION: (1)...(396)
<400> SEQUENCE: 28
gga tcc ctt gag gat ggg gaa atg ata gat ac
#a ggc tat ggt gcc atg       48
Gly Ser Leu Glu Asp Gly Glu Met Ile Asp Th
#r Gly Tyr Gly Ala Met
1               5
#                 10
#                 15
gac ttt cgt aca ttg cag gaa acc aaa agt ga
#g gta cca cta gat att       96
Asp Phe Arg Thr Leu Gln Glu Thr Lys Ser Gl
#u Val Pro Leu Asp Ile
20
#             25
#             30
tgc caa tcc gtg tgt aaa tat cct gat tat tt
#g cag atg tct gct gat      144
Cys Gln Ser Val Cys Lys Tyr Pro Asp Tyr Le
#u Gln Met Ser Ala Asp
35
#         40
#         45
gta tat ggg gac agt atg ttt ttt tgt ttg cg
#c aag gaa cag ttg ttt      192
Val Tyr Gly Asp Ser Met Phe Phe Cys Leu Ar
#g Lys Glu Gln Leu Phe
50
#     55
#     60
gcc agg cac ttt tgg aat aga ggt ggc atg gt
#g ggc gac aca ata cct      240
Ala Arg His Phe Trp Asn Arg Gly Gly Met Va
#l Gly Asp Thr Ile Pro
65
# 70
# 75
# 80
tca gag tta tat att aaa ggc acg gat ata cg
#t gag cgt cct ggt act      288
Ser Glu Leu Tyr Ile Lys Gly Thr Asp Ile Ar
#g Glu Arg Pro Gly Thr
85
#                 90
#                 95
cat gta tat tcc cct tcc cca agt ggc tct at
#g gtc tct tct gat tcc      336
His Val Tyr Ser Pro Ser Pro Ser Gly Ser Me
#t Val Ser Ser Asp Ser
100
#           105
#           110
cag ttg ttt aat aag ccc tat tgg ttg cat aa
#g gcc caa ggc cac aat      384
Gln Leu Phe Asn Lys Pro Tyr Trp Leu His Ly
#s Ala Gln Gly His Asn
115
#       120
#       125
aac ggg atg gat cc
#
#
#    398
Asn Gly Met Asp
130
<210> SEQ ID NO 29
<211> LENGTH: 132
<212> TYPE: PRT
<213> ORGANISM: Papilloma virus
<400> SEQUENCE: 29
Gly Ser Leu Glu Asp Gly Glu Met Ile Asp Th
#r Gly Tyr Gly Ala Met
1               5
#                10
#                15
Asp Phe Arg Thr Leu Gln Glu Thr Lys Ser Gl
#u Val Pro Leu Asp Ile
20
#            25
#            30
Cys Gln Ser Val Cys Lys Tyr Pro Asp Tyr Le
#u Gln Met Ser Ala Asp
35
#        40
#        45
Val Tyr Gly Asp Ser Met Phe Phe Cys Leu Ar
#g Lys Glu Gln Leu Phe
50
#    55
#    60
Ala Arg His Phe Trp Asn Arg Gly Gly Met Va
#l Gly Asp Thr Ile Pro
65
#70
#75
#80
Ser Glu Leu Tyr Ile Lys Gly Thr Asp Ile Ar
#g Glu Arg Pro Gly Thr
85
#                90
#                95
His Val Tyr Ser Pro Ser Pro Ser Gly Ser Me
#t Val Ser Ser Asp Ser
100
#           105
#           110
Gln Leu Phe Asn Lys Pro Tyr Trp Leu His Ly
#s Ala Gln Gly His Asn
115
#       120
#       125
Asn Gly Met Asp
130
<210> SEQ ID NO 30
<211> LENGTH: 398
<212> TYPE: DNA
<213> ORGANISM: Papilloma virus
<400> SEQUENCE: 30
ggatccatcc cgttattgtg gccttgggcc ttatgcaacc aatagggctt at
#taaacaac     60
tgggaatcag aagagaccat agagccactt ggggaagggg aatatacatg ag
#taccagga    120
cgctcacgta tatccgtgcc tttaatatat aactctgaag gtattgtgtc gc
#ccaccatg    180
ccacctctat tccaaaagtg cctggcaaac aactgttcct tgcgcaaaca aa
#aaaacata    240
ctgtccccat atacatcagc agacatctgc aaataatcag gatatttaca ca
#cggattgg    300
caaatatcta gtggtacctc acttttggtt tcctgcaatg tacgaaagtc ca
#tggcacca    360
tagcctgtat ctatcatttc cccatcctca agggatcc
#
#    398

Claims

1. A polypeptide encoded by the nucleotide sequence of SEQ ID NO:7, SEQ ID NO:10, SEQ ID NO:13, or SEQ ID NO:16.

2. A polypeptide encoded by a polynucleotide hybridizing to the complement of the nucleotide sequence of SEQ ID NO:7, SEQ ID NO:10, SEQ ID NO:13, or SEQ ID NO:16, wherein the polynucleotide has at least 90% identity to the nucleotide sequence of SEQ ID NO:7, SEQ ID NO:10, SEQ ID NO:13, or SEQ ID NO:16.

3. An isolated polypeptide consisting of the amino acid sequence selected from SEQ ID NO:7, SEQ ID NO:10, SEQ ID NO:13, or SEQ ID NO:16.

4. A composition comprising the polypeptide of any one of claim 1, 2, or 3 as reagent for diagnosis, treatment and/or vaccination, and a pharmaceutically acceptable carrier.

5. A pharmaceutical composition comprising the polypeptide of any one of claim 1, 2, or 3 and a pharmaceutically acceptable carrier.

6. A method of vaccinating a subject in need against papillomavirus, comprising administering to the subject the composition of claim 4.

7. A method of vaccinating a subject in need against papillomavirus, comprising administering to the subject the composition of claim 5.

8. A method of treating a subject in need against papillomavirus, comprising administering to the subject the composition of claim 4.

9. A method of treating a subject in need against papillomavirus, comprising administering to the subject the composition of claim 5.

10. A diagnostic kit to detect papillomavirus infection wherein the kit comprises the polypeptide of any one of claim 1, 2, or 3 as reagent for diagnosis.