Papilloma viruses, products for the detection thereof as well as for treating diseases caused by them

I. FIELD OF THE INVENTION

This invention relates to a DNA coding for a peptide of a papilloma virus major capsid protein and a papilloma virus genome, respectively. In addition, this invention concerns proteins coded by the papilloma virus genome and antibodies directed against them as well as 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, 1996,

Biochimica et Biophysica Acta

(

BBA

) 1288:55-78). HP viruses are also considered for the growth of malignant tumors in the oropharyngeal zone (zur Hausen, 1977

, Curr. Top. Microbiol. Immunol.

78:1-30).

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.

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.

According to the invention, this is achieved by providing the subject matters in the claims.

III. SUMMARY OF THE INVENTION

This invention relates to a DNA coding for a peptide of a papilloma virus major capsid protein and a papilloma virus genome, respectively. Furthermore, this invention concerns proteins coded by the papilloma virus genome and antibodies directed thereagainst as well as 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 DL17 with DSM (

Deutsche Sammlung von Mikroorganismen und Zellkulturen

(German-type collection of micro-organisms and cell cultures)) under DSM 11180 on Sep. 17, 1996.

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 DL20 with DSM under DSM 11181 on Sep. 17, 1996.

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 DL27 with DSM under DSM 11182 on Sep. 17, 1996.

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 D135 with DSM under DSM 11183 on Sep. 17, 1996.

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 DL40 with DSM under DSM 11184 on Sep. 17, 1996.

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 DL78 with DSM under DSM 11185 on Sep. 17, 1996.

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 DL82 with DSM under DSM 11186 on Sep. 17, 1996.

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 DL83 with DSM under DSM 11187 on Sep. 17, 1996.

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 DL84 with DSM under DSM 11188 on Sep. 17, 1996.

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 papilloma virus. This DNA was deposited as plasmid DL100 with DSM under DSM 11189 on Sep. 17, 1996.

FIG. 11

shows the base sequence (SEQ ID NOS:31 and 33) and the amino acid sequence (SEQ ID NO:32), derived therefrom, of a DNA coding for a peptide of L1 of a papilloma virus. This DNA was deposited as plasmid HR22 with DSM under DSM 11190 on Sep. 17, 1996.

V. DETAILED DESCRIPTION OF THE INVENTION

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

(SEQ ID NO:2),

FIG. 2

(SEQ ID NO:5),

FIG. 3

(SEQ ID NO:8),

FIG. 4

(SEQ ID NO:11),

FIG. 5

(SEQ ID NO:14),

FIG. 6

(SEQ ID NO:17),

FIG. 7

(SEQ ID NO:20),

FIG. 8

(SEQ ID NO:23),

FIG. 9

(SEQ ID NO:26),

FIG. 10

(SEQ ID NO:29) or

FIG. 11

(SEQ ID NO:32) 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

(SEQ ID NOS:1 and 3),

FIG. 2

(SEQ ID NOS:4 and 6),

FIG. 3

(SEQ ID NOS:7 and 9),

FIG. 4

(SEQ ID NOS:10 and 12),

FIG. 5

(SEQ ID NOS:13 and 15),

FIG. 6

(SEQ ID NOS:16 and 18),

FIG. 7

(SEQ ID NOS:19 and 21),

FIG. 8

(SEQ ID NOS:22 and 24),

FIG. 9

(SEQ ID NOS:25 and 27),

FIG. 10

(SEQ ID NOS:28 and 30) or

FIG. 11

(SEQ ID NOS:31 and 33) or a base sequence differing therefrom by one or more base pairs.

The above DNA was compared with the DNA of known papilloma viruses. Sequence homology studies were carried out. A homology having less than 90% shows that a DNA according to the invention is a new HP virus. The DNAs according to the invention have the following sequence homologies with respect to known papilloma viruses:

DNA of FIG.

1

: 67% with respect to HP virus 65

DNA of FIG.

2

: 62% with respect to HP virus 17

DNA of FIG.

3

: 78% with respect to HP virus 65

DNA of FIG.

4

: |

DNA of FIG.

5

: 86% with respect to HP virus 10

DNA of FIG.

6

: 86% with respect to HP virus 10

DNA of

FIG. 7

; 62% with respect to HP virus 8

DNA of FIG.

8

: 66% with respect to HP virus 65

DNA of FIG.

9

: 64% with respect to HP virus 65

DNA of FIG.

10

: 75% with respect to HP virus 15

DNA of FIG.

11

: 81% with respect to HP virus 22 and 23, respectively.

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 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 arts 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, JM109, 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. It is favorable to use a process 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 extra chromosomal DNA, respectively. Examples of such vectors are cosmids such as pWE15 and Super Cos1, and phages such as λ-phages, e.g. λZAP expressvector, 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 extra chromosomal 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 DL17-G 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 electrophoretically 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 DL17-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: DL20-G, DL27-G, DL35-G, DL40-G, DL78-G, DL82-G, DL-83G, DL84-G, DL100-G and HR22-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 DL17-G is described by way of example. For this purpose, the HP virus 65 related to the DNA of

FIG. 1

(SEQ ID NOS:1 and 3) 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 DL17-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 DL17-G-L1 DNA and the DNA coding for L2 is referred to as DL17-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 particular, reference is made to the vector pGEX-2T as regards the expression in

E. coli

(Kirnbauer et al., supra). Having inserted the DL17-G-L1 DNA and DL17-G-L2 DNA, one obtains pGEX-2T-DL17-G-L1 and pGEX-2T-DL17-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.-DL17-G-L1 and pEVmod.-DL17-C-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 DL17-G-L1 and DL17-G-L2 DNAs jointly in the expression vector pSynwtVI

−

and using the resulting pSynwtVI

−

DL17-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 DL17-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 DL17-G

The total DNA is isolated from a biopsy of a squamous cell carcinoma. 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

(SEQ ID NOS:1 and 3) is used in combination with the HP virus-65 DNA as p

32

-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.

B. Example 2

Cloning of the Papilloma Virus Genome DL17-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 p

32

-labeled DNA of

FIG. 1

(SEQ ID NOS:1 and 3) employed in Example 1 in combination with p

32

-labeled HP virus-65 DNA. Hybridization with corresponding phage plaques is obtained. The BamHI fragments of DL17-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 DL17-G is identified. The plasmid of this bacterial clone is referred to as pBlue-DL17-G.

All references cited within the body of the instant specification are hereby incorporated by reference in their entirety.

33

1

416

DNA

Papilloma virus

CDS

(1)...(414)

1
ctc gag gat ggg gaa atg tgc gat att gga ttt gga gca tgc aat ttt 48
Leu Glu Asp Gly Glu Met Cys Asp Ile Gly Phe Gly Ala Cys Asn Phe
1 5 10 15
aaa cag tta cag aag gat aga tct ggt gtt cca tta gat ata gta gag 96
Lys Gln Leu Gln Lys Asp Arg Ser Gly Val Pro Leu Asp Ile Val Glu
20 25 30
agc act tgt aag tat cct gat ttt tta aag atg ggt aag gat atg tat 144
Ser Thr Cys Lys Tyr Pro Asp Phe Leu Lys Met Gly Lys Asp Met Tyr
35 40 45
ggc gac gag cta ttt ttc tat ggc aga cga gaa cag tta tat gta aga 192
Gly Asp Glu Leu Phe Phe Tyr Gly Arg Arg Glu Gln Leu Tyr Val Arg
50 55 60
cat aac ttt tct cgt gca ggc act gta gga gat agt ata cct tta cct 240
His Asn Phe Ser Arg Ala Gly Thr Val Gly Asp Ser Ile Pro Leu Pro
65 70 75 80
gat cag gat act gca ttt tat aga agt cct aat act gca aat aat gat 288
Asp Gln Asp Thr Ala Phe Tyr Arg Ser Pro Asn Thr Ala Asn Asn Asp
85 90 95
ttg cct caa aat aca tta gcg tct cac ata tac tgt gcc atc cca agt 336
Leu Pro Gln Asn Thr Leu Ala Ser His Ile Tyr Cys Ala Ile Pro Ser
100 105 110
ggt tct tta acc agt agt gat tct caa tta ttt aat agg cct tat tgg 384
Gly Ser Leu Thr Ser Ser Asp Ser Gln Leu Phe Asn Arg Pro Tyr Trp
115 120 125
ctg caa aat gct cag ggc acc aac aac ggc gt 416
Leu Gln Asn Ala Gln Gly Thr Asn Asn Gly
130 135

2

138

PRT

Papilloma virus

2
Leu Glu Asp Gly Glu Met Cys Asp Ile Gly Phe Gly Ala Cys Asn Phe
1 5 10 15
Lys Gln Leu Gln Lys Asp Arg Ser Gly Val Pro Leu Asp Ile Val Glu
20 25 30
Ser Thr Cys Lys Tyr Pro Asp Phe Leu Lys Met Gly Lys Asp Met Tyr
35 40 45
Gly Asp Glu Leu Phe Phe Tyr Gly Arg Arg Glu Gln Leu Tyr Val Arg
50 55 60
His Asn Phe Ser Arg Ala Gly Thr Val Gly Asp Ser Ile Pro Leu Pro
65 70 75 80
Asp Gln Asp Thr Ala Phe Tyr Arg Ser Pro Asn Thr Ala Asn Asn Asp
85 90 95
Leu Pro Gln Asn Thr Leu Ala Ser His Ile Tyr Cys Ala Ile Pro Ser
100 105 110
Gly Ser Leu Thr Ser Ser Asp Ser Gln Leu Phe Asn Arg Pro Tyr Trp
115 120 125
Leu Gln Asn Ala Gln Gly Thr Asn Asn Gly
130 135

3

416

DNA

Papilloma virus

3
acgccgttgt tggtgccctg agcattttgc agccaataag gcctattaaa taattgagaa 60
tcactactgg ttaaagaacc acttgggatg gcacagtata tgtgagacgc taatgtattt 120
tgaggcaaat cattatttgc agtattagga cttctataaa atgcagtatc ctgatcaggt 180
aaaggtatac tatctcctac agtgcctgca cgagaaaagt tatgtcttac atataactgt 240
tctcgtctgc catagaaaaa tagctcgtcg ccatacatat ccttacccat ctttaaaaaa 300
tcaggatact tacaagtgct ctctactata tctaatggaa caccagatct atccttctgt 360
aactgtttaa aattgcatgc tccaaatcca atatcgcaca tttccccatc ctcgag 416

4

386

DNA

Papilloma virus

CDS

(1)...(384)

4
att gag gat ggt gat atg gta gac ata gga ttt ggg aat tgt aat ttt 48
Ile Glu Asp Gly Asp Met Val Asp Ile Gly Phe Gly Asn Cys Asn Phe
1 5 10 15
aaa gct tta caa cag gac aag gct ggt acg cct tta gag tta act aat 96
Lys Ala Leu Gln Gln Asp Lys Ala Gly Thr Pro Leu Glu Leu Thr Asn
20 25 30
gaa aaa tgt aag tgg cca gat ttt ctg aag atg gaa aaa gac act tat 144
Glu Lys Cys Lys Trp Pro Asp Phe Leu Lys Met Glu Lys Asp Thr Tyr
35 40 45
gga gac cag atg ttt ttc tgt ggc agg aag gag caa atg tat tct agg 192
Gly Asp Gln Met Phe Phe Cys Gly Arg Lys Glu Gln Met Tyr Ser Arg
50 55 60
cat atg ctt gct aaa gcg ggt att gat ggt gat cat ata cca gaa tca 240
His Met Leu Ala Lys Ala Gly Ile Asp Gly Asp His Ile Pro Glu Ser
65 70 75 80
tta tac cat tcg cca aag aat aat gga aat ggc att gct cct tac act 288
Leu Tyr His Ser Pro Lys Asn Asn Gly Asn Gly Ile Ala Pro Tyr Thr
85 90 95
tac ttt cca acc aca agc ggt tcc tta gtc aca agt gat aat caa tta 336
Tyr Phe Pro Thr Thr Ser Gly Ser Leu Val Thr Ser Asp Asn Gln Leu
100 105 110
ttt aac agg cca tat tgg ctt cat aat tca caa gga acc aat aac ggt 384
Phe Asn Arg Pro Tyr Trp Leu His Asn Ser Gln Gly Thr Asn Asn Gly
115 120 125
at 386

5

128

PRT

Papilloma virus

5
Ile Glu Asp Gly Asp Met Val Asp Ile Gly Phe Gly Asn Cys Asn Phe
1 5 10 15
Lys Ala Leu Gln Gln Asp Lys Ala Gly Thr Pro Leu Glu Leu Thr Asn
20 25 30
Glu Lys Cys Lys Trp Pro Asp Phe Leu Lys Met Glu Lys Asp Thr Tyr
35 40 45
Gly Asp Gln Met Phe Phe Cys Gly Arg Lys Glu Gln Met Tyr Ser Arg
50 55 60
His Met Leu Ala Lys Ala Gly Ile Asp Gly Asp His Ile Pro Glu Ser
65 70 75 80
Leu Tyr His Ser Pro Lys Asn Asn Gly Asn Gly Ile Ala Pro Tyr Thr
85 90 95
Tyr Phe Pro Thr Thr Ser Gly Ser Leu Val Thr Ser Asp Asn Gln Leu
100 105 110
Phe Asn Arg Pro Tyr Trp Leu His Asn Ser Gln Gly Thr Asn Asn Gly
115 120 125

6

386

DNA

Papilloma virus

6
ataccgttat tggttccttg tgaattatga agccaatatg gcctgttaaa taattgatta 60
tcacttgtga ctaaggaacc gcttgtggtt ggaaagtaag tgtaaggagc aatgccattt 120
ccattattct ttggcgaatg gtataatgat tctggtatat gatcaccatc aatacccgct 180
ttagcaagca tatgcctaga atacatttgc tccttcctgc cacagaaaaa catctggtct 240
ccataagtgt ctttttccat cttcagaaaa tctggccact tacatttttc attagttaac 300
tctaaaggcg taccagcctt gtcctgttgt aaagctttaa aattacaatt cccaaatcct 360
atgtctacca tatcaccatc ctcaat 386

7

410

DNA

Papilloma virus

CDS

(1)...(408)

7
ctg gag gat ggc gac atg tgt gat ata ggc ttt gga gct ttt aac ttt 48
Leu Glu Asp Gly Asp Met Cys Asp Ile Gly Phe Gly Ala Phe Asn Phe
1 5 10 15
aaa gct ttg cag gat gat aaa tcc agt gca cca tta gat gta gtt ggt 96
Lys Ala Leu Gln Asp Asp Lys Ser Ser Ala Pro Leu Asp Val Val Gly
20 25 30
act ttg tgt aaa tgg cct gac ttc tta aag atg agt aag gac att tat 144
Thr Leu Cys Lys Trp Pro Asp Phe Leu Lys Met Ser Lys Asp Ile Tyr
35 40 45
ggt gac agt tta ttc ttc ttt ggc cga agg gaa cag ctt tat gca aga 192
Gly Asp Ser Leu Phe Phe Phe Gly Arg Arg Glu Gln Leu Tyr Ala Arg
50 55 60
cac ttt ttt gtt aga gct ggg aca atg ggt gat gcg tta cca gag cct 240
His Phe Phe Val Arg Ala Gly Thr Met Gly Asp Ala Leu Pro Glu Pro
65 70 75 80
ttt gaa gtg aag tct gat tac ata att gct gct cag agt aac caa gaa 288
Phe Glu Val Lys Ser Asp Tyr Ile Ile Ala Ala Gln Ser Asn Gln Glu
85 90 95
caa aat aat ctt ggc cct cac att tat ttt gga act cct agc ggt tct 336
Gln Asn Asn Leu Gly Pro His Ile Tyr Phe Gly Thr Pro Ser Gly Ser
100 105 110
ctt gta tca agt gaa tct cag ctt ttt aac cga ccg tat tgg tta aac 384
Leu Val Ser Ser Glu Ser Gln Leu Phe Asn Arg Pro Tyr Trp Leu Asn
115 120 125
aga gct cag ggc act aat aac ggc at 410
Arg Ala Gln Gly Thr Asn Asn Gly
130 135

8

136

PRT

Papilloma virus

8
Leu Glu Asp Gly Asp Met Cys Asp Ile Gly Phe Gly Ala Phe Asn Phe
1 5 10 15
Lys Ala Leu Gln Asp Asp Lys Ser Ser Ala Pro Leu Asp Val Val Gly
20 25 30
Thr Leu Cys Lys Trp Pro Asp Phe Leu Lys Met Ser Lys Asp Ile Tyr
35 40 45
Gly Asp Ser Leu Phe Phe Phe Gly Arg Arg Glu Gln Leu Tyr Ala Arg
50 55 60
His Phe Phe Val Arg Ala Gly Thr Met Gly Asp Ala Leu Pro Glu Pro
65 70 75 80
Phe Glu Val Lys Ser Asp Tyr Ile Ile Ala Ala Gln Ser Asn Gln Glu
85 90 95
Gln Asn Asn Leu Gly Pro His Ile Tyr Phe Gly Thr Pro Ser Gly Ser
100 105 110
Leu Val Ser Ser Glu Ser Gln Leu Phe Asn Arg Pro Tyr Trp Leu Asn
115 120 125
Arg Ala Gln Gly Thr Asn Asn Gly
130 135

9

410

DNA

Papilloma virus

9
atgccgttat tagtgccctg agctctgttt aaccaatacg gtcggttaaa aagctgagat 60
tcacttgata caagagaacc gctaggagtt ccaaaataaa tgtgagggcc aagattattt 120
tgttcttggt tactctgagc agcaattatg taatcagact tcacttcaaa aggctctggt 180
aacgcatcac ccattgtccc agctctaaca aaaaagtgtc ttgcataaag ctgttccctt 240
cggccaaaga agaataaact gtcaccataa atgtccttac tcatctttaa gaagtcaggc 300
catttacaca aagtaccaac tacatctaat ggtgcactgg atttatcatc ctgcaaagct 360
ttaaagttaa aagctccaaa gcctatatca cacatgtcgc catcctccag 410

10

383

DNA

Papilloma virus

CDS

(1)...(381)

10
ata gag gat ggg gaa atg gtt gaa act ggg ttc ggg gcc ctg gat ttt 48
Ile Glu Asp Gly Glu Met Val Glu Thr Gly Phe Gly Ala Leu Asp Phe
1 5 10 15
gcc gct cta cag tcc aac aaa tct gat gtc ccc ctg gat att tgt act 96
Ala Ala Leu Gln Ser Asn Lys Ser Asp Val Pro Leu Asp Ile Cys Thr
20 25 30
aac ata tgt aaa tat ccg gac tat ctg aaa atg gct gct gac ccc tat 144
Asn Ile Cys Lys Tyr Pro Asp Tyr Leu Lys Met Ala Ala Asp Pro Tyr
35 40 45
ggc gat tct atg ttc ttt tcc ctg cgc agg gag cag atg ttc acc cgg 192
Gly Asp Ser Met Phe Phe Ser Leu Arg Arg Glu Gln Met Phe Thr Arg
50 55 60
cat ttc ttc aat cgg ggt ggg tcg atg ggt gac gcc ctc ccg gag gag 240
His Phe Phe Asn Arg Gly Gly Ser Met Gly Asp Ala Leu Pro Glu Glu
65 70 75 80
cta tac gtc aaa agt tct acc gtg cag acc cca ggt agt tat gtt tac 288
Leu Tyr Val Lys Ser Ser Thr Val Gln Thr Pro Gly Ser Tyr Val Tyr
85 90 95
acc tcc act ccc agt ggc tct atg gta tcc tct gaa cag cag tta ttt 336
Thr Ser Thr Pro Ser Gly Ser Met Val Ser Ser Glu Gln Gln Leu Phe
100 105 110
aac aag cct tac tgg ctg cgg agg gct caa ggt act aat aac ggc 381
Asn Lys Pro Tyr Trp Leu Arg Arg Ala Gln Gly Thr Asn Asn Gly
115 120 125
gt 383

11

127

PRT

Papilloma virus

11
Ile Glu Asp Gly Glu Met Val Glu Thr Gly Phe Gly Ala Leu Asp Phe
1 5 10 15
Ala Ala Leu Gln Ser Asn Lys Ser Asp Val Pro Leu Asp Ile Cys Thr
20 25 30
Asn Ile Cys Lys Tyr Pro Asp Tyr Leu Lys Met Ala Ala Asp Pro Tyr
35 40 45
Gly Asp Ser Met Phe Phe Ser Leu Arg Arg Glu Gln Met Phe Thr Arg
50 55 60
His Phe Phe Asn Arg Gly Gly Ser Met Gly Asp Ala Leu Pro Glu Glu
65 70 75 80
Leu Tyr Val Lys Ser Ser Thr Val Gln Thr Pro Gly Ser Tyr Val Tyr
85 90 95
Thr Ser Thr Pro Ser Gly Ser Met Val Ser Ser Glu Gln Gln Leu Phe
100 105 110
Asn Lys Pro Tyr Trp Leu Arg Arg Ala Gln Gly Thr Asn Asn Gly
115 120 125

12

383

DNA

Papilloma virus

12
acgccgttat tagtaccttg agccctccgc agccagtaag gcttgttaaa taactgctgt 60
tcagaggata ccatagagcc actgggagtg gaggtgtaaa cataactacc tggggtctgc 120
acggtagaac ttttgacgta tagctcctcc gggagggcgt cacccatcga cccaccccga 180
ttgaagaaat gccgggtgaa catctgctcc ctgcgcaggg aaaagaacat agaatcgcca 240
taggggtcag cagccatttt cagatagtcc ggatatttac atatgttagt acaaatatcc 300
agggggacat cagatttgtt ggactgtaga gcggcaaaat ccagggcccc gaacccagtt 360
tcaaccattt ccccatcctc tat 383

13

386

DNA

Papilloma virus

CDS

(1)...(384)

13
atg gaa gac gga gat atg gta gac act ggc tat ggt gct atg gac ttc 48
Met Glu Asp Gly Asp Met Val Asp Thr Gly Tyr Gly Ala Met Asp Phe
1 5 10 15
act gca tta cag tta aat aag tct gac gtg cct ata gat att tgc cag 96
Thr Ala Leu Gln Leu Asn Lys Ser Asp Val Pro Ile Asp Ile Cys Gln
20 25 30
tcc act tgt aaa tac cct gat tat ttg ggc atg gca gca gag cct tat 144
Ser Thr Cys Lys Tyr Pro Asp Tyr Leu Gly Met Ala Ala Glu Pro Tyr
35 40 45
ggc gac agc atg ttt ttt tat ttg cgc aga gag caa ctg ttt gca aga 192
Gly Asp Ser Met Phe Phe Tyr Leu Arg Arg Glu Gln Leu Phe Ala Arg
50 55 60
cat ttt ttc aat aga gcc agt gca gtg gga gac acc att cct gac act 240
His Phe Phe Asn Arg Ala Ser Ala Val Gly Asp Thr Ile Pro Asp Thr
65 70 75 80
tta ata ttg aag tcg gcc agt ggt gac caa aac gtt ggt agt gct gtg 288
Leu Ile Leu Lys Ser Ala Ser Gly Asp Gln Asn Val Gly Ser Ala Val
85 90 95
tat agc ccc act ccc agt ggg tcc atg gta aca tct gag gct caa tta 336
Tyr Ser Pro Thr Pro Ser Gly Ser Met Val Thr Ser Glu Ala Gln Leu
100 105 110
ttt aat aag cca tat tgg ctg aag cgg gct caa gga cat aac aat ggt 384
Phe Asn Lys Pro Tyr Trp Leu Lys Arg Ala Gln Gly His Asn Asn Gly
115 120 125
gt 386

14

128

PRT

Papilloma virus

14
Met Glu Asp Gly Asp Met Val Asp Thr Gly Tyr Gly Ala Met Asp Phe
1 5 10 15
Thr Ala Leu Gln Leu Asn Lys Ser Asp Val Pro Ile Asp Ile Cys Gln
20 25 30
Ser Thr Cys Lys Tyr Pro Asp Tyr Leu Gly Met Ala Ala Glu Pro Tyr
35 40 45
Gly Asp Ser Met Phe Phe Tyr Leu Arg Arg Glu Gln Leu Phe Ala Arg
50 55 60
His Phe Phe Asn Arg Ala Ser Ala Val Gly Asp Thr Ile Pro Asp Thr
65 70 75 80
Leu Ile Leu Lys Ser Ala Ser Gly Asp Gln Asn Val Gly Ser Ala Val
85 90 95
Tyr Ser Pro Thr Pro Ser Gly Ser Met Val Thr Ser Glu Ala Gln Leu
100 105 110
Phe Asn Lys Pro Tyr Trp Leu Lys Arg Ala Gln Gly His Asn Asn Gly
115 120 125

15

386

DNA

Papilloma virus

15
acaccattgt tatgtccttg agcccgcttc agccaatatg gcttattaaa taattgagcc 60
tcagatgtta ccatggaccc actgggagtg gggctataca cagcactacc aacgttttgg 120
tcaccactgg ccgacttcaa tattaaagtg tcaggaatgg tgtctcccac tgcactggct 180
ctattgaaaa aatgtcttgc aaacagttgc tctctgcgca aataaaaaaa catgctgtcg 240
ccataaggct ctgctgccat gcccaaataa tcagggtatt tacaagtgga ctggcaaata 300
tctataggca cgtcagactt atttaactgt aatgcagtga agtccatagc accatagcca 360
gtgtctacca tatctccgtc ttccat 386

16

386

DNA

Papilloma virus

CDS

(1)...(384)

16
ctg gag gat gcg gaa atg gta gac act gga tat ggt gcc atg gac ttt 48
Leu Glu Asp Ala Glu Met Val Asp Thr Gly Tyr Gly Ala Met Asp Phe
1 5 10 15
act gca tta cag tta aat aag tct gac gtg cct atc gat att tgc cag 96
Thr Ala Leu Gln Leu Asn Lys Ser Asp Val Pro Ile Asp Ile Cys Gln
20 25 30
tct acc tgt aaa tat cct gat tat ttg ggc atg gca gca gag cct tat 144
Ser Thr Cys Lys Tyr Pro Asp Tyr Leu Gly Met Ala Ala Glu Pro Tyr
35 40 45
ggc gac agc atg ttt ttt tat ttg cgc agg gaa caa ctg ttt gcc aga 192
Gly Asp Ser Met Phe Phe Tyr Leu Arg Arg Glu Gln Leu Phe Ala Arg
50 55 60
cat ttt ttt aat agg gct agt gca gtt ggg gac acc att cct gac act 240
His Phe Phe Asn Arg Ala Ser Ala Val Gly Asp Thr Ile Pro Asp Thr
65 70 75 80
ttg ata ttg aag gca gcc agt gga ggg caa aac gtt ggt agt gct gtt 288
Leu Ile Leu Lys Ala Ala Ser Gly Gly Gln Asn Val Gly Ser Ala Val
85 90 95
tac agc ccc aca ccc agt ggg tcc atg gta aca tct gag gct caa ttg 336
Tyr Ser Pro Thr Pro Ser Gly Ser Met Val Thr Ser Glu Ala Gln Leu
100 105 110
ttt aat aag cca tat tgg cta cgg cgg gct caa gga acg aac aac gga 384
Phe Asn Lys Pro Tyr Trp Leu Arg Arg Ala Gln Gly Thr Asn Asn Gly
115 120 125
gt 386

17

128

PRT

Papilloma virus

17
Leu Glu Asp Ala Glu Met Val Asp Thr Gly Tyr Gly Ala Met Asp Phe
1 5 10 15
Thr Ala Leu Gln Leu Asn Lys Ser Asp Val Pro Ile Asp Ile Cys Gln
20 25 30
Ser Thr Cys Lys Tyr Pro Asp Tyr Leu Gly Met Ala Ala Glu Pro Tyr
35 40 45
Gly Asp Ser Met Phe Phe Tyr Leu Arg Arg Glu Gln Leu Phe Ala Arg
50 55 60
His Phe Phe Asn Arg Ala Ser Ala Val Gly Asp Thr Ile Pro Asp Thr
65 70 75 80
Leu Ile Leu Lys Ala Ala Ser Gly Gly Gln Asn Val Gly Ser Ala Val
85 90 95
Tyr Ser Pro Thr Pro Ser Gly Ser Met Val Thr Ser Glu Ala Gln Leu
100 105 110
Phe Asn Lys Pro Tyr Trp Leu Arg Arg Ala Gln Gly Thr Asn Asn Gly
115 120 125

18

386

DNA

Papilloma virus

18
actccgttgt tcgttccttg agcccgccgt agccaatatg gcttattaaa caattgagcc 60
tcagatgtta ccatggaccc actgggtgtg gggctgtaaa cagcactacc aacgttttgc 120
cctccactgg ctgccttcaa tatcaaagtg tcaggaatgg tgtccccaac tgcactagcc 180
ctattaaaaa aatgtctggc aaacagttgt tccctgcgca aataaaaaaa catgctgtcg 240
ccataaggct ctgctgccat gcccaaataa tcaggatatt tacaggtaga ctggcaaata 300
tcgataggca cgtcagactt atttaactgt aatgcagtaa agtccatggc accatatcca 360
gtgtctacca tttccgcatc ctccag 386

19

413

DNA

Papilloma virus

CDS

(1)...(411)

19
atc gag gat ggg gat atg tgt gat att ggt ttt gga aac atg aat ttc 48
Ile Glu Asp Gly Asp Met Cys Asp Ile Gly Phe Gly Asn Met Asn Phe
1 5 10 15
agt ata tta caa caa gac aga tca ggt gtt cct ttg gat ata gta gct 96
Ser Ile Leu Gln Gln Asp Arg Ser Gly Val Pro Leu Asp Ile Val Ala
20 25 30
tcc att tgc aaa tgg cca gat ctt ggt aaa atg acc aat gat gtg tat 144
Ser Ile Cys Lys Trp Pro Asp Leu Gly Lys Met Thr Asn Asp Val Tyr
35 40 45
ggt gat gaa cta ttc ttt ttt ggt aaa cgg gag cag gtt tat gca agg 192
Gly Asp Glu Leu Phe Phe Phe Gly Lys Arg Glu Gln Val Tyr Ala Arg
50 55 60
cat tat ttt aca agg cat ggt gtt gta gga gaa gat att cct cag gta 240
His Tyr Phe Thr Arg His Gly Val Val Gly Glu Asp Ile Pro Gln Val
65 70 75 80
aat gag gac cct aca act aaa tac ctg cga gga ggt gaa ggt ggt caa 288
Asn Glu Asp Pro Thr Thr Lys Tyr Leu Arg Gly Gly Glu Gly Gly Gln
85 90 95
aat cag gct act gtt tca tcc tct gta tat ttt gca act ccc agt ggt 336
Asn Gln Ala Thr Val Ser Ser Ser Val Tyr Phe Ala Thr Pro Ser Gly
100 105 110
tcc ttg gtg tcc agt gat gct caa att atg aac agg cct tat tgg gta 384
Ser Leu Val Ser Ser Asp Ala Gln Ile Met Asn Arg Pro Tyr Trp Val
115 120 125
caa cgc gcg cag gga acg aac aac ggc gt 413
Gln Arg Ala Gln Gly Thr Asn Asn Gly
130 135

20

137

PRT

Papilloma virus

20
Ile Glu Asp Gly Asp Met Cys Asp Ile Gly Phe Gly Asn Met Asn Phe
1 5 10 15
Ser Ile Leu Gln Gln Asp Arg Ser Gly Val Pro Leu Asp Ile Val Ala
20 25 30
Ser Ile Cys Lys Trp Pro Asp Leu Gly Lys Met Thr Asn Asp Val Tyr
35 40 45
Gly Asp Glu Leu Phe Phe Phe Gly Lys Arg Glu Gln Val Tyr Ala Arg
50 55 60
His Tyr Phe Thr Arg His Gly Val Val Gly Glu Asp Ile Pro Gln Val
65 70 75 80
Asn Glu Asp Pro Thr Thr Lys Tyr Leu Arg Gly Gly Glu Gly Gly Gln
85 90 95
Asn Gln Ala Thr Val Ser Ser Ser Val Tyr Phe Ala Thr Pro Ser Gly
100 105 110
Ser Leu Val Ser Ser Asp Ala Gln Ile Met Asn Arg Pro Tyr Trp Val
115 120 125
Gln Arg Ala Gln Gly Thr Asn Asn Gly
130 135

21

413

DNA

Papilloma virus

21
acgccgttgt tcgttccctg cgcgcgttgt acccaataag gcctgttcat aatttgagca 60
tcactggaca ccaaggaacc actgggagtt gcaaaatata cagaggatga aacagtagcc 120
tgattttgac caccttcacc tcctcgcagg tatttagttg tagggtcctc atttacctga 180
ggaatatctt ctcctacaac accatgcctt gtaaaataat gccttgcata aacctgctcc 240
cgtttaccaa aaaagaatag ttcatcacca tacacatcat tggtcatttt accaagatct 300
ggccatttgc aaatggaagc tactatatcc aaaggaacac ctgatctgtc ttgttgtaat 360
atactgaaat tcatgtttcc aaaaccaata tcacacatat ccccatcctc gat 413

22

395

DNA

Papilloma virus

CDS

(1)...(393)

22
ctg gag gat ggc gac atg tgt gat gta gga ttt gga gct gca aat ttt 48
Leu Glu Asp Gly Asp Met Cys Asp Val Gly Phe Gly Ala Ala Asn Phe
1 5 10 15
aaa aca ctt cag gaa gat aaa tca gga gta cct atg gat ctt tta aat 96
Lys Thr Leu Gln Glu Asp Lys Ser Gly Val Pro Met Asp Leu Leu Asn
20 25 30
gaa act tgt aaa tat cct gac ttt ctt cag atg tca aaa gac aaa tat 144
Glu Thr Cys Lys Tyr Pro Asp Phe Leu Gln Met Ser Lys Asp Lys Tyr
35 40 45
gga gac agt ttg ttc ttt ttt gga aga aag gaa caa ctt tac gcg aga 192
Gly Asp Ser Leu Phe Phe Phe Gly Arg Lys Glu Gln Leu Tyr Ala Arg
50 55 60
cac ttt tat gtt aga gga ggt gtt gat ggc gat gca ttg cca tta act 240
His Phe Tyr Val Arg Gly Gly Val Asp Gly Asp Ala Leu Pro Leu Thr
65 70 75 80
aac ttt att tat ggt gct cag cag gac aaa cct caa aac aat tta gga 288
Asn Phe Ile Tyr Gly Ala Gln Gln Asp Lys Pro Gln Asn Asn Leu Gly
85 90 95
cca tat act tac ttt cct act cct agt ggc tct tta tac tca acc gat 336
Pro Tyr Thr Tyr Phe Pro Thr Pro Ser Gly Ser Leu Tyr Ser Thr Asp
100 105 110
aat caa tta ttt aac aga ccc tat tgg ctt agc cag gct cag ggc aca 384
Asn Gln Leu Phe Asn Arg Pro Tyr Trp Leu Ser Gln Ala Gln Gly Thr
115 120 125
aac aat ggg at 395
Asn Asn Gly
130

23

131

PRT

Papilloma virus

23
Leu Glu Asp Gly Asp Met Cys Asp Val Gly Phe Gly Ala Ala Asn Phe
1 5 10 15
Lys Thr Leu Gln Glu Asp Lys Ser Gly Val Pro Met Asp Leu Leu Asn
20 25 30
Glu Thr Cys Lys Tyr Pro Asp Phe Leu Gln Met Ser Lys Asp Lys Tyr
35 40 45
Gly Asp Ser Leu Phe Phe Phe Gly Arg Lys Glu Gln Leu Tyr Ala Arg
50 55 60
His Phe Tyr Val Arg Gly Gly Val Asp Gly Asp Ala Leu Pro Leu Thr
65 70 75 80
Asn Phe Ile Tyr Gly Ala Gln Gln Asp Lys Pro Gln Asn Asn Leu Gly
85 90 95
Pro Tyr Thr Tyr Phe Pro Thr Pro Ser Gly Ser Leu Tyr Ser Thr Asp
100 105 110
Asn Gln Leu Phe Asn Arg Pro Tyr Trp Leu Ser Gln Ala Gln Gly Thr
115 120 125
Asn Asn Gly
130

24

395

DNA

Papilloma virus

24
atcccattgt ttgtgccctg agcctggcta agccaatagg gtctgttaaa taattgatta 60
tcggttgagt ataaagagcc actaggagta ggaaagtaag tatatggtcc taaattgttt 120
tgaggtttgt cctgctgagc accataaata aagttagtta atggcaatgc atcgccatca 180
acacctcctc taacataaaa gtgtctcgcg taaagttgtt cctttcttcc aaaaaagaac 240
aaactgtctc catatttgtc ttttgacatc tgaagaaagt caggatattt acaagtttca 300
tttaaaagat ccataggtac tcctgattta tcttcctgaa gtgttttaaa atttgcagct 360
ccaaatccta catcacacat gtcgccatcc tccag 395

25

407

DNA

Papilloma virus

CDS

(1)...(405)

25
cta gaa gac gcg gag atg agt gat att ggt ttg ggg gca gtt aat ttt 48
Leu Glu Asp Ala Glu Met Ser Asp Ile Gly Leu Gly Ala Val Asn Phe
1 5 10 15
cat acg ttt tcg gcc tcc cgt tca gat gct cct tta gaa gtt ata gat 96
His Thr Phe Ser Ala Ser Arg Ser Asp Ala Pro Leu Glu Val Ile Asp
20 25 30
tca att tgc aaa tgg cct gat ttt gtt cag atg aca aaa gat gtt tat 144
Ser Ile Cys Lys Trp Pro Asp Phe Val Gln Met Thr Lys Asp Val Tyr
35 40 45
gga gat aag atc tgg ttt tat gga aaa cgg gaa cag ctt tat gcc aga 192
Gly Asp Lys Ile Trp Phe Tyr Gly Lys Arg Glu Gln Leu Tyr Ala Arg
50 55 60
cat atg ttt gtt aag gat ggt gtg gac ggt gac agt att cca aat gag 240
His Met Phe Val Lys Asp Gly Val Asp Gly Asp Ser Ile Pro Asn Glu
65 70 75 80
ccc aca cac gct tat tat att ccc cca ccc aca ggt tct gcc cag gaa 288
Pro Thr His Ala Tyr Tyr Ile Pro Pro Pro Thr Gly Ser Ala Gln Glu
85 90 95
act aat ttt gga aag ata agt tac ttt cca gtt ccc agt gga tct ttg 336
Thr Asn Phe Gly Lys Ile Ser Tyr Phe Pro Val Pro Ser Gly Ser Leu
100 105 110
gtg tcc agt gag gct act ata ttt aat aga cct tat tgg ttg cac aaa 384
Val Ser Ser Glu Ala Thr Ile Phe Asn Arg Pro Tyr Trp Leu His Lys
115 120 125
gct caa gga aca aac aat gga at 407
Ala Gln Gly Thr Asn Asn Gly
130 135

26

135

PRT

Papilloma virus

26
Leu Glu Asp Ala Glu Met Ser Asp Ile Gly Leu Gly Ala Val Asn Phe
1 5 10 15
His Thr Phe Ser Ala Ser Arg Ser Asp Ala Pro Leu Glu Val Ile Asp
20 25 30
Ser Ile Cys Lys Trp Pro Asp Phe Val Gln Met Thr Lys Asp Val Tyr
35 40 45
Gly Asp Lys Ile Trp Phe Tyr Gly Lys Arg Glu Gln Leu Tyr Ala Arg
50 55 60
His Met Phe Val Lys Asp Gly Val Asp Gly Asp Ser Ile Pro Asn Glu
65 70 75 80
Pro Thr His Ala Tyr Tyr Ile Pro Pro Pro Thr Gly Ser Ala Gln Glu
85 90 95
Thr Asn Phe Gly Lys Ile Ser Tyr Phe Pro Val Pro Ser Gly Ser Leu
100 105 110
Val Ser Ser Glu Ala Thr Ile Phe Asn Arg Pro Tyr Trp Leu His Lys
115 120 125
Ala Gln Gly Thr Asn Asn Gly
130 135

27

407

DNA

Papilloma virus

27
attccattgt ttgttccttg agctttgtgc aaccaataag gtctattaaa tatagtagcc 60
tcactggaca ccaaagatcc actgggaact ggaaagtaac ttatctttcc aaaattagtt 120
tcctgggcag aacctgtggg tgggggaata taataagcgt gtgtgggctc atttggaata 180
ctgtcaccgt ccacaccatc cttaacaaac atatgtctgg cataaagctg ttcccgtttt 240
ccataaaacc agatcttatc tccataaaca tcttttgtca tctgaacaaa atcaggccat 300
ttgcaaattg aatctataac ttctaaagga gcatctgaac gggaggccga aaacgtatga 360
aaattaactg cccccaaacc aatatcactc atctccgcgt cttctag 407

28

413

DNA

Papilloma virus

CDS

(1)...(411)

28
att gag gac ggt gat atg atc gat att ggg ttt ggc aat ata aat aac 48
Ile Glu Asp Gly Asp Met Ile Asp Ile Gly Phe Gly Asn Ile Asn Asn
1 5 10 15
aag aca tta tca gta aac aaa tca gat gtt agt tta gat tta gta aat 96
Lys Thr Leu Ser Val Asn Lys Ser Asp Val Ser Leu Asp Leu Val Asn
20 25 30
gaa ata gct aaa tat cca gat ttt tta aca atg gct aat gat gtg tat 144
Glu Ile Ala Lys Tyr Pro Asp Phe Leu Thr Met Ala Asn Asp Val Tyr
35 40 45
ggc gat tct tgc ttt ttt ttt gcc agg aga gaa caa tgt tat gct aga 192
Gly Asp Ser Cys Phe Phe Phe Ala Arg Arg Glu Gln Cys Tyr Ala Arg
50 55 60
cat tat ttt act aga gga gga gct gtg ggt gat gct ata cct gat aca 240
His Tyr Phe Thr Arg Gly Gly Ala Val Gly Asp Ala Ile Pro Asp Thr
65 70 75 80
aca act aat caa gat cac aaa tac tat cta gca cct aag agt gga caa 288
Thr Thr Asn Gln Asp His Lys Tyr Tyr Leu Ala Pro Lys Ser Gly Gln
85 90 95
tcc caa agt cct ttg ggt aat tct att tac tat ccc acc gtt agt ggc 336
Ser Gln Ser Pro Leu Gly Asn Ser Ile Tyr Tyr Pro Thr Val Ser Gly
100 105 110
tcc tta gtt tct tct gat gca cag ctc ttt aac aga ccc ttc tgg ttg 384
Ser Leu Val Ser Ser Asp Ala Gln Leu Phe Asn Arg Pro Phe Trp Leu
115 120 125
aaa cgt gca cag ggg cac aat aac ggc at 413
Lys Arg Ala Gln Gly His Asn Asn Gly
130 135

29

137

PRT

Papilloma virus

29
Ile Glu Asp Gly Asp Met Ile Asp Ile Gly Phe Gly Asn Ile Asn Asn
1 5 10 15
Lys Thr Leu Ser Val Asn Lys Ser Asp Val Ser Leu Asp Leu Val Asn
20 25 30
Glu Ile Ala Lys Tyr Pro Asp Phe Leu Thr Met Ala Asn Asp Val Tyr
35 40 45
Gly Asp Ser Cys Phe Phe Phe Ala Arg Arg Glu Gln Cys Tyr Ala Arg
50 55 60
His Tyr Phe Thr Arg Gly Gly Ala Val Gly Asp Ala Ile Pro Asp Thr
65 70 75 80
Thr Thr Asn Gln Asp His Lys Tyr Tyr Leu Ala Pro Lys Ser Gly Gln
85 90 95
Ser Gln Ser Pro Leu Gly Asn Ser Ile Tyr Tyr Pro Thr Val Ser Gly
100 105 110
Ser Leu Val Ser Ser Asp Ala Gln Leu Phe Asn Arg Pro Phe Trp Leu
115 120 125
Lys Arg Ala Gln Gly His Asn Asn Gly
130 135

30

413

DNA

Papilloma virus

30
atgccgttat tgtgcccctg tgcacgtttc aaccagaagg gtctgttaaa gagctgtgca 60
tcagaagaaa ctaaggagcc actaacggtg ggatagtaaa tagaattacc caaaggactt 120
tgggattgtc cactcttagg tgctagatag tatttgtgat cttgattagt tgttgtatca 180
ggtatagcat cacccacagc tcctcctcta gtaaaataat gtctagcata acattgttct 240
ctcctggcaa aaaaaaagca agaatcgcca tacacatcat tagccattgt taaaaaatct 300
ggatatttag ctatttcatt tactaaatct aaactaacat ctgatttgtt tactgataat 360
gtcttgttat ttatattgcc aaacccaata tcgatcatat caccgtcctc aat 413

31

404

DNA

Papilloma virus

CDS

(1)...(402)

31
ata cag gat ggg gac atg ttt gat ata ggt ttt ggt aat att aac aat 48
Ile Gln Asp Gly Asp Met Phe Asp Ile Gly Phe Gly Asn Ile Asn Asn
1 5 10 15
aaa act cta tct tat aat aag tct gat gta agt tta gac att gtt aat 96
Lys Thr Leu Ser Tyr Asn Lys Ser Asp Val Ser Leu Asp Ile Val Asn
20 25 30
gaa gta tgc aaa tat cca gat ttt ttg aca atg tct aat gat gtg tat 144
Glu Val Cys Lys Tyr Pro Asp Phe Leu Thr Met Ser Asn Asp Val Tyr
35 40 45
gga gac gca tgc ttt tac tgt gcc cga aga gag caa tgt tat gct aga 192
Gly Asp Ala Cys Phe Tyr Cys Ala Arg Arg Glu Gln Cys Tyr Ala Arg
50 55 60
cat tat ttt gtt cgg gga ggt cag gtt gga gat gca ata cct gac gag 240
His Tyr Phe Val Arg Gly Gly Gln Val Gly Asp Ala Ile Pro Asp Glu
65 70 75 80
gca gtc caa caa gat cac aaa tat tat tta cct tct gat aca cgg cgc 288
Ala Val Gln Gln Asp His Lys Tyr Tyr Leu Pro Ser Asp Thr Arg Arg
85 90 95
act tta gaa aac tcc acc tat ttt ccc acc gta agc ggg tcg ttg gtg 336
Thr Leu Glu Asn Ser Thr Tyr Phe Pro Thr Val Ser Gly Ser Leu Val
100 105 110
acc tct gat gcc caa cta ttt aat agg ccc ttt tgg tta aaa cgt gca 384
Thr Ser Asp Ala Gln Leu Phe Asn Arg Pro Phe Trp Leu Lys Arg Ala
115 120 125
caa ggc cac aat aac gga at 404
Gln Gly His Asn Asn Gly
130

32

134

PRT

Papilloma virus

32
Ile Gln Asp Gly Asp Met Phe Asp Ile Gly Phe Gly Asn Ile Asn Asn
1 5 10 15
Lys Thr Leu Ser Tyr Asn Lys Ser Asp Val Ser Leu Asp Ile Val Asn
20 25 30
Glu Val Cys Lys Tyr Pro Asp Phe Leu Thr Met Ser Asn Asp Val Tyr
35 40 45
Gly Asp Ala Cys Phe Tyr Cys Ala Arg Arg Glu Gln Cys Tyr Ala Arg
50 55 60
His Tyr Phe Val Arg Gly Gly Gln Val Gly Asp Ala Ile Pro Asp Glu
65 70 75 80
Ala Val Gln Gln Asp His Lys Tyr Tyr Leu Pro Ser Asp Thr Arg Arg
85 90 95
Thr Leu Glu Asn Ser Thr Tyr Phe Pro Thr Val Ser Gly Ser Leu Val
100 105 110
Thr Ser Asp Ala Gln Leu Phe Asn Arg Pro Phe Trp Leu Lys Arg Ala
115 120 125
Gln Gly His Asn Asn Gly
130

33

404

DNA

Papilloma virus

33
attccgttat tgtggccttg tgcacgtttt aaccaaaagg gcctattaaa tagttgggca 60
tcagaggtca ccaacgaccc gcttacggtg ggaaaatagg tggagttttc taaagtgcgc 120
cgtgtatcag aaggtaaata atatttgtga tcttgttgga ctgcctcgtc aggtattgca 180
tctccaacct gacctccccg aacaaaataa tgtctagcat aacattgctc tcttcgggca 240
cagtaaaagc atgcgtctcc atacacatca ttagacattg tcaaaaaatc tggatatttg 300
catacttcat taacaatgtc taaacttaca tcagacttat tataagatag agttttattg 360
ttaatattac caaaacctat atcaaacatg tccccatcct gtat 404

Number	Date	Country
WO 9530754	Nov 1995	WO
WO 9704099	Feb 1997	WO

Papilloma viruses, products for the detection thereof as well as for treating diseases caused by them

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Entry
de Villiers et al., 1997, “Prevailing papillomaviurs types in non-melanoma carcinomas of the skin in renal allograft recipients,”International Journal of Cancer 73(3):356-361.
Hagensee et al., 1993, “Self-assembly of human papillomavirus type 1 capsids by expression of the L1 protein alone or by coexpression of the L1 and L2 capsid proteins,” Journal of Virology 67(1):315-322.
Kirnbauer et al., 1993, “Effecient self-assembly of human papillomavirus type 16 L1 and L1-L2 into virus-like particles,” Journal of Virology 67(12):6929-6936.
zur Hausen, 1977, “Human papillomavirus and their possible role in squamous cell carcinomas,” Curr. Top. Microbiol. Immunol. 78:1-30.
zur Hausen, 1996, “Papillomavirus infections—a major cause of human cancers,” Biochimica et Biophysica Acta 1288(2):F55-F78.