LOCUS HPV66 7824 bp ds-DNA VRL 04-JUL-1995 DEFINITION Human papillomavirus type 66 (HPV66), complete genome. ACCESSION U31794 SOURCE Human papillomavirus type 66 DNA. ORGANISM Human papillomavirus type 66 Viridae; ds-DNA nonenveloped viruses; Papovaviridae; Papillomavirus. REFERENCE 1 (bases 1 to 7824) AUTHORS Delius,H. TITLE Direct Submission JOURNAL Unpublished COMMENT HPV66 was originally isolated from a biopsy of a 38-year-old patient with a stage I invasive squamous-cell carcinoma of the uterine cervix. Cloned HPV66 DNA was obtained from the Papillomavirus Reference Center, Heidelberg and subsequently sequenced by Dr. H. Delius. The sample was coinfected with HPV16, HPV45 and the new HPV66. The HPV16 was present in an integrated form; HPV45 and HPV66 were present in episomal (circular) form. The biopsy specimen showed a low-grade intraepithelial neoplasia which continues as a poorly differentiated invasive carcinoma. HPV66, but not HPV45 nor HPV16, was detectable by in-situ hybridization in the nuclei of terminally differentiating cells of the CIN; Tawheed et al (J. Clin. Micro. 29, 2656-2660) took this to suggest that HPV66 has oncogenic potential. Screening of 160 anogenital biopsies revealed the presence of HPV66 in three cases of high-grade CIN and one PIN. HPV16, HPV51, and HPV58 were also each detected in one of these HPV66 positive lesions. Putative splice sites suggest that HPV66, like many other genital carcinoma-associated HPV types, encodes both a full-length and a truncated form of the E6 protein. The LXCXE motif associated with binding of p105-RB in HPV16 E7 is preserved. HPV66 hybridized with high stringency with HPV56, and more weakly with HPV30 and HPV53. Phylogenetic analysis supports this grouping. No conserved restriction sites between HPV56 and HPV66 were found. HPV66 was isolated on two occasions by independent researchers. Dr. M. Manos isolated the same strain from a patient with normal cytology and designated it PAP88. It was later discovered that the PAP88 sequence was identical to the sequence of HPV66 (M. Van Ranst, personal communication). Tachezy et al (Biochem. Biophys. Res. Comm. 204, 820-827) isolated a variant of HPV66, designated AE3 (U01533). FEATURES Location/Qualifiers CDS 102..569 /note="ORF E6 from bp 96 to 569" /product="transforming protein" /gene="E6" /note="putative" /codon_start=1 /translation="MDSIFSNTQERPRSLHHLSEVLQIPLLDLRLSCVYCKKELTSLE LYRFACIELKLVYRNNWPYAVCRVCLLFYSKVRKYRYYKYSVYGATLESITKKQLSDL SIRCYRCQCPLTPEEKQLHCEHKRRFHYIAYAWTGSCLQCWRHTSRQATESTV" CDS 572..889 /note="ORF E7 from bp 545 to 889" /product="transforming protein" /gene="E7" /note="putative" /codon_start=1 /translation="MHGKVPTLQEVILELAPQTEIDLQCNEQLDSSEDEDEDEIDHLL ERPQQARQAEQHKCYLIHVPCCKCELVVQLDIQSTKEELRVVQQLLMGALTVTCPLCA SSK" CDS 895..2787 /note="ORF E1 from bp 886 to 2787" /product="replication protein" /gene="E1" /note="putative" /codon_start=1 /translation="MASPEGTDGEGMGCCGWFQVEAIVERKTGDTISDDESEEENETD TDVDGFIDNTLINNTQEDRETAQQLLQVQTAHADAQTLQKLKRKYIGSPLSDISNQQT VYREEVKRRLILSEDSGYGNTLETLETSQQVEYEKGNGCGSSQNGGSQNSNCSEHSVS NMDIDTNMETPTHQLQELFKSSNVQGRLHFKFKEVYGVPYTELVRTFKSDSTCCNDWI CAIFGVNETLAEALKTILKPQCVYYHMQCLTCSWGVIVMMLIRYICGKNRKTITKSLS SILNVPQEQMLIQPPKLRSPAVALYFYKTAMSNISEVYGETPEWIQRQTQLQHSLQDN QFELSKMVQWAFDNEVTDDSQIAFLYAQLADIDSNAQAFLKSNMQAKYVKDCGIMCRH YKRAQQQQMNMCQWIKHICSKVDEGGDWKPIVQFLRYQGVDFISFLSYFKLFLQGTPK HNCLVLCGPPNTGKSCFAMSLINFFQGSVISFVNSQSHFWLQPLDNAKLGLLDDATDT CWRYIDDYLRNLLDGNPISLDRKHKQLVQIKCPPVIITTNVNPMQDAKLRYLHSRISV FKFENPFPLDNNGNPVYELSNVNWKCFFERTWSRLNLDNDEDKENNGDSIPTFRCVPE QNTRLL" CDS 2729..3838 /note="ORF E2 from bp 2699 to 3838" /product="regulatory protein" /gene="E2" /note="putative" /codon_start=1 /translation="METLSQRLDACQNKILDCYEKDSKCIIDHIDYWKAVRHEYVLYY KARENDINVLNHQMVPSLQVCKAKACSAIELQIALEAISNTIYKNEEWTLRDTCDELW RTEPKNCFKKEGQHIEVWFDGNKNNCMEYVVWKFIYYNGECGWCKVSSGVDYRGIYYM HDGHKTYYTDFEQEAKKYGCTNIWEVHMETESIYCPDSVSSTCRYNVPPVETVNEYNN HRTTTTASTFVGAQDAAVSHRPGKRPRASESEPDSSRESYAHCVTTDTDISNNANSRS PRINTQSHCGDKTTPVIHLKGEANRLKCCRYRFQKYKTLFTDVTTTYHWTSTDNKDSS IITILYKDETQRDTFLNVVKIPPSVQVILGQMSCP" CDS <3081..3605 /note="ORF E4 from bp 3081 to 3605" /gene="E4" /note="putative" /codon_start=1 /translation="KCGLMVTKIIVWNMWCGNLYIIMESVGGVKCHQGWITEAYIICM MATKHITQTLNRRPKNMGVQTYGKYIWKPRVFTVLTLCLVPVDTTYPLLRLLTNTTTT GPPPPPPPLWAPKTPRYPTDQENDPEQVNQNLTPPESPTHTVSQQTQTSVTTPTVEVH VSTHKATVVIKLRL" CDS <3994..4251 /note="ORF E5 from bp 3994 to 4251" /gene="E5" /note="putative" /codon_start=1 /translation="SPYIATIDFCVICVFALCFCVCLCVCHFVPLLLSASLFTSCLIL IILFWFVVATSFFDTFILFLLFFYIPTLCIYCHALWLINHL" CDS 4272..5666 /note="ORF L2 from bp 4167 to 5666" /product="minor capsid protein" /gene="L2" /note="putative" /codon_start=1 /translation="MVAHRATRRKRASATQLYKTCKLSGTCPEDVINKVEQKTWADRI LQWGSLFTYFGGLGIGTGSGSGGRAGYVPLGSRPSTIVDVTPARPPIVVESVGPTDPS IVTLVEESSVINSGAGVPNFTGSGGFEVTSSSTTTPAVLDITPTSSTVHVSSTTITNP LYIDPPVIEAPQTGEVSGNILISTPTSGIHSYEEIPMQTFAIHGTGNEPISSTPIPGF RRLAAPRLYSRAFQQVRVTDPAFLDNPTTLISADNPVFEGADTTLTFSPSGVAPDPDF MDIVALHRPAFTTRRTGVRFSRLGKKATMQTRRGTQIGARVHYYYDISPIAQADEIEM QPLLSTDNSFDGLYDIYANIDDEAPISFRQSGATPSAQLPIKPSTLSFASNTANVTAP LGNVWETPFYSGPDIVLPTGPSTWPFVPQSPSDVTHDVYIQGATFALWPVYFFKRRRR KRIPYFFADGDVAA" CDS 5647..7158 /note="ORF L1 from bp 5494 to 7158" /product="major capsid protein" /gene="L1" /note="putative" /codon_start=1 /translation="MAMWRPSDNKVYLPPTPVSKVVATDTYVKRTSIFYHAGSSRLLA VGHPYYSVSKSGTKTNIPKVSAYQYRVFRVRLPDPNKFGLPDPSFYNPDQERLVWACV GLEVGRGQPLGAGLSGHPLFNRLDDTEVSNLAGNNVIEDSRDNISVDCKQTQLCIVGC APALGEHWTKGAVCKSTPGNTGDCPPLALVNTPIEDGDMVDTGFGAMDFKLLQESKAE VPLDIVQSTCKYPDYLKMSADAYGDSMWFYLRREQLFARHYFNRAGNVGEAIPTDLYW KGGNGRDPPPSSVYVATPSGSMITSEAQLFNKPYWLQRAQGHNNGICWGNQVFVTVVD TTRSTNMTINAAKSTLTKYDAREINQYLRHVEEYELQFVFQLCKITLTAEVMAYLHNM NNTLLDDWNIGLSPPVATSLEDKYRYIKSTAITCQREQPPAEKQDPLAKYKFWEVNLQ DSFSADLDQFPLGRKFLMQLGPRPPRPKASVSASKRRAAPTSSSSSPAKRKKR" BASE COUNT 2471 a 1355 c 1653 g 2345 t ORIGIN 1 gaaagtttca atcatacttt attatattgg gagtaaccga aatgggttta ggaccgaaaa 61 cggtacatat aaaaggcagc ctgttgtgcc tgtagatatc catggattcc atattcagca 121 atacacagga acgtccacga agcctgcacc atctgagcga ggtattacaa atacctttac 181 ttgatcttag attatcatgt gtatactgca aaaaggaact tacaagttta gagctatata 241 ggtttgcatg tattgagtta aaactagtat atagaaacaa ttggccatat gcagtatgta 301 gggtatgttt attgttttat agtaaggtta gaaaatatag gtactataaa tattcagtgt 361 atggggcaac attagaaagt ataactaaaa aacagttatc tgatttatca ataaggtgct 421 accgatgtca atgtccgtta acaccggagg aaaaacaatt gcactgtgaa cataaaagac 481 gatttcatta tatagcatat gcatggaccg ggtcatgttt gcagtgttgg agacatacga 541 gtagacaagc tacagaatct acagtataac catgcatggt aaagtaccaa cgttgcaaga 601 ggttatatta gaacttgcac cgcaaacgga aattgaccta caatgcaatg agcaattgga 661 cagctcagag gatgaggatg aggatgaaat agaccatttg ctggagcggc cacagcaagc 721 tagacaagct gaacaacata agtgttacct aattcacgta ccttgttgta agtgtgagtt 781 ggtggtgcag ttggacattc agagtaccaa agaggagcta cgtgtggtac aacagctgct 841 tatgggtgcg ttaacagtaa cgtgcccact ctgcgcatca tctaaataac tgcaatggca 901 tcacctgaag gtacagatgg ggaggggatg ggatgttgtg gatggtttca ggtagaagca 961 attgtagaaa gaaaaacggg ggatacaata tcagatgatg aaagcgagga ggagaatgaa 1021 acagatacag atgtagatgg atttatagac aatacactta taaacaatac acaggaagac 1081 agggagacag ctcaacaatt attgcaagta caaacagcac atgcagatgc acagacgttg 1141 caaaaactaa aacgaaagta tataggtagt cccttaagtg atattagtaa tcagcaaact 1201 gtgtaccgag aggaagtaaa acgaaggcta atattatcag aagacagcgg gtatggcaat 1261 acattggaaa cattggaaac atcacaacag gtagaatacg aaaagggaaa tgggtgcggg 1321 agctcacaaa atggaggctc gcaaaacagt aattgtagtg agcactcggt atcaaatatg 1381 gatatagata caaatatgga aacaccaaca caccaattgc aggaactatt taaaagtagt 1441 aacgtacaag gaagattaca ttttaaattt aaagaagtgt atggagtgcc atatacagag 1501 ttggtgcgaa catttaaaag cgatagtaca tgttgtaacg attggatatg tgcaatattt 1561 ggcgttaatg aaacattagc agaggcgtta aaaactatac taaaaccaca atgtgtgtac 1621 tatcatatgc aatgcttaac atgttcatgg ggagtaattg taatgatgct aattagatat 1681 atatgtggaa aaaatagaaa aacaattaca aaatcgctaa gctcaatttt aaatgtacca 1741 caagagcaaa tgttaattca accaccaaaa ctacgaagtc ctgctgtagc attatatttt 1801 tataaaacag caatgtcaaa tattagtgag gtgtatgggg aaacaccaga atggatacaa 1861 agacagacac aattgcaaca cagtttacaa gacaatcaat ttgaattgtc taaaatggta 1921 cagtgggcat ttgataatga agtaacagat gatagccaaa ttgccttttt atatgcacaa 1981 ctagcagaca tagatagcaa tgcacaagca tttttaaaaa gtaatatgca agcaaaatat 2041 gtaaaggatt gtggaataat gtgtagacat tacaaaaggg cacagcaaca gcaaatgaat 2101 atgtgccagt ggataaagca tatatgtagt aaagtagatg aagggggtga ttggaaaccc 2161 attgtgcaat ttttacgata tcaaggggtc gacttcattt catttttaag ttattttaaa 2221 ttatttttac aaggaacgcc taaacataat tgtttggtac tgtgtggacc accaaataca 2281 ggtaaatcat gttttgctat gagccttata aattttttcc aagggtcagt catttcattt 2341 gttaattcac aaagccactt ttggttacag ccactagaca atgccaaatt aggtttgctg 2401 gatgatgcaa cagatacgtg ttggagatac atagatgatt atctaagaaa tttattagat 2461 gggaatccca taagtttaga taggaaacat aaacaattag tacaaataaa atgtcctcca 2521 gttattatta caactaatgt aaatcctatg caagatgcaa aattaagata tttacacagt 2581 agaatttcag tgtttaagtt tgaaaatcca tttccattag ataacaatgg taatcctgtg 2641 tatgaattaa gtaatgtaaa ttggaaatgt ttttttgaaa ggacatggtc cagattaaat 2701 ttggataacg acgaggacaa agaaaacaat ggagactcta tcccaacgtt tagatgcgtg 2761 ccagaacaaa atactagact gttatgaaaa agatagtaaa tgcattatag atcacataga 2821 ctattggaaa gctgtacgac atgaatatgt attatattat aaagcaagag aaaatgacat 2881 taatgtacta aaccaccaga tggtgccctc tttacaagtg tgtaaagcaa aagcatgtag 2941 tgcaatagaa ttacaaatag cactggaagc aataagtaac acaatatata aaaatgaaga 3001 gtggacatta cgtgatacat gtgatgaact gtggcgcacg gagcctaaaa actgttttaa 3061 aaaagaagga caacacatag aagtgtggtt tgatggtaac aaaaataatt gtatggaata 3121 tgtggtgtgg aaatttatat attataatgg agagtgtggg tggtgtaaag tgtcatcagg 3181 ggtggattac agaggcatat attatatgca tgatggccac aaaacatatt acacagactt 3241 tgaacaggag gccaaaaaat atgggtgtac aaacatatgg gaagtacata tggaaaccga 3301 gagtatttac tgtcctgact ctgtgtctag tacctgtaga tacaacgtac cccctgttga 3361 gactgttaac gaatacaaca accacaggac caccaccacc gcctccacct ttgtgggcgc 3421 ccaagacgcc gcggtatccc acagaccagg aaaacgaccc agagcaagtg aatcagaacc 3481 tgactcctcc agagagtcct acgcacactg tgtcacaaca gacacagaca tcagtaacaa 3541 cgccaacagt agaagtccac gtatcaacac acaaagccac tgtggtgata aaactacgcc 3601 tgtaatccat ttaaaaggtg aagctaatag attaaagtgt tgtagataca gatttcaaaa 3661 atataaaaca ttatttacag atgtaacaac aacatatcat tggacaagta cagataataa 3721 agacagtagt attattacaa tattatataa agatgaaaca caacgggaca cctttttaaa 3781 tgttgtaaaa ataccaccta gtgtacaggt tattttggga caaatgagtt gtccataaag 3841 tgttgtatat attgtatata catatgtgtt attgtaacac tggtacaggt gaagtgtaat 3901 tgccatacat tgctgctaag catatatatt gcacccatta attgtatttg gtatattatg 3961 tgttattgta acactgggaa aggtaacgtg taatcgccat atattgcaac cattgatttt 4021 tgtgtaattt gtgtgtttgc gctttgcttt tgtgtttgtc tgtgtgtgtg ccattttgtc 4081 ccgcttttgc tatctgcatc tttatttaca agttgtctta tactaattat tttattttgg 4141 tttgttgtgg ctacatcatt ttttgatact tttatactgt ttttactatt tttttatata 4201 cctacactgt gtatatattg ccatgctttg tggttaataa accatttgta acagtagtaa 4261 tttttgctac tatggttgcc caccgtgcca cacgacgcaa acgcgcatct gccacacaat 4321 tatataaaac atgcaaatta tctggtacat gtcctgagga tgttattaat aaggtggagc 4381 aaaaaacatg ggctgatagg attttacaat ggggaagttt atttacatat tttggggggc 4441 ttggcattgg tactgggtct gggtcgggtg gtcgggcggg ctatgttccc ttaggctcta 4501 ggccttctac tatagttgat gtcactcctg cacgaccacc tattgtggtg gagtcagttg 4561 ggcctacaga tccttctatt gttacactgg tagaagaatc tagtgttatt aactcagggg 4621 ctggtgttcc caattttact gggtcagggg gatttgaagt tacatcctct tccacaacca 4681 cacctgctgt gttggatatt acacccacat ctagtactgt acatgtaagt agtactacta 4741 taacaaaccc actatatatt gatcctccag taattgaggc tccacaaact ggagaggtat 4801 ctggtaatat tttgattagc actcctacat ctggaataca tagctatgag gaaataccta 4861 tgcaaacatt tgctatacac ggtactggca acgaacctat tagtagtacc cctattccag 4921 gttttagacg ccttgctgct cccaggttat atagtagggc ttttcagcag gttagggtca 4981 ctgacccagc atttttggac aaccccacaa cattaatatc tgctgataat cctgtttttg 5041 aaggtgctga cacaacgttg accttttctc cctcgggtgt ggctcctgat cctgatttta 5101 tggatatagt tgcattacat aggcctgcat ttactacacg tagaacaggt gtgcgtttta 5161 gtaggctagg caaaaaggct accatgcaaa cacgtagggg tacgcaaata ggtgctcgtg 5221 tgcattatta ttatgatata agtcctattg cacaggctga tgaaattgaa atgcagccat 5281 tattgtctac agacaattca tttgatggcc tatatgatat ttatgcaaat attgatgatg 5341 aggcacccat ttcatttcgt cagtctggtg ctacaccttc tgcacaatta cctattaaac 5401 cttctacatt atcctttgct agtaacacag ctaatgttac tgcccctttg ggaaatgttt 5461 gggaaacacc attttattca ggtcctgata tagttttacc tacaggcccc agtacttggc 5521 ccttcgtacc tcagtctcct tctgatgtta cacatgatgt atatatacag ggagctacat 5581 ttgcactatg gcctgtatat ttttttaaac gtaggcgccg taaacgtatt ccctattttt 5641 ttgcagatgg cgatgtggcg gcctagtgac aataaggtgt acctacctcc aacacctgtt 5701 tcaaaggttg tggcaacgga tacatatgta aaacgtacca gtatatttta tcatgcaggt 5761 agctctaggt tgcttgctgt tggccatcct tattactctg tttccaaatc tggtaccaaa 5821 acaaacatcc ctaaagttag tgcatatcag tatagagtgt ttagggtacg gttgcctgat 5881 cctaataagt ttggccttcc tgatccatct ttctataatc ctgaccagga acgtttggta 5941 tgggcctgtg taggtttgga ggtaggccga ggtcaacctt taggtgctgg gttaagtggt 6001 catccattat ttaataggct ggatgacact gaggtctcta atttagcagg taataatgtt 6061 atagaagata gccgggacaa tatatctgtt gattgtaaac aaacccagtt atgtattgtg 6121 ggatgtgcac cagcattagg ggaacattgg actaagggcg cggtgtgtaa gtctacacca 6181 ggtaatacag gggattgtcc acctcttgca ttagttaata ccccgataga ggacggtgac 6241 atggtggaca ccgggtttgg tgcaatggac tttaagctat tacaggaatc aaaggctgag 6301 gtgccattgg acattgtaca atctacatgt aaatatcctg attatttaaa aatgtctgca 6361 gatgcctatg gggattctat gtggttttac ttacgcaggg aacaattgtt tgccagacat 6421 tactttaata gggcaggtaa tgttggggaa gccattccta cagatttgta ttggaagggt 6481 ggcaatggca gggaccctcc tcccagttct gtatatgttg ctactcctag tgggtccatg 6541 attacctctg aggcccaatt atttaataaa ccttattggt tgcaacgtgc acagggccat 6601 aataatggca tatgctgggg taatcaggta tttgttactg ttgtggatac taccagaagc 6661 accaacatga ctattaatgc agctaaaagc acattaacta aatatgatgc ccgtgaaatc 6721 aatcaatacc ttcgccatgt ggaggaatat gaactacagt ttgtgtttca actttgtaaa 6781 ataaccttaa ctgcagaagt tatggcatat ttgcataata tgaataatac tttattagac 6841 gattggaata ttggcttatc cccaccagtt gcaactagct tagaggataa atataggtat 6901 attaaaagca cagctattac atgtcagagg gaacagcccc ctgcagaaaa gcaggatccc 6961 ctggctaaat ataagttttg ggaagttaat ttacaggaca gcttttctgc agacctggat 7021 cagtttcctt tgggtagaaa atttttaatg caactaggcc ctagaccccc tagacccaag 7081 gctagtgtat ctgcctctaa aaggcgggcg gctcctacct cttcctcttc ttcaccagct 7141 aaacgtaaaa aacgatagtt gtgtgttgtg tgttgtatgt attgtatggt tgtgcttgta 7201 ctgtatgttt ttgtgtatgt ttatgtattt tataattgtg tatgtgctat gtgtatgtat 7261 gactgtatgt atgtgtaatg ttttgtgtgt atgtaataaa catgcatggt tacttttacg 7321 cgtggttgca taaactaagg tgcggtagta tccttgggca gtgtgtgtca ggttaggtgg 7381 tgttccttac tgtttaatgt tatattaaat aggttgtttg tatgcactat agtaacacac 7441 caaactccat tttagtgctg tacgccattt tatgcatgca accgaattcg gttgcctagc 7501 cttttgtcct tatttaaacc caaaacgact tttcagcaaa acagttaatc ctttggcata 7561 ttgccgtttc ctgttgtatg attcaggtat gtacactgcc ttaccctgta ttactcacct 7621 gtatttctgt gccaactatg cttttatctg catactttgg cgctgttggg catatgtttt 7681 tatgcaggtg tttgcaatat attttgttgg cgtgtagccc ttattgtata agccaagtat 7741 ctgtcttgca aatatgtaac catatactta ctcattttac aaaaccgttt acggtcgtgc 7801 taaaacaggt ttcttttaat tgtt