{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T16:05:59Z","timestamp":1649174759136},"reference-count":61,"publisher":"Microbiology Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,10,1]]},"abstract":"<jats:p>We previously isolated human papillomavirus 83 (HPV83m) from a cervical smear. Sequence analysis of E6 and E7 proteins highlighted five mutations located in the second putative zinc-finger region of E6 (E6m), an important domain for protein\u2013protein or protein\u2013DNA interactions. Here, we show that E6m of HPV83m can trigger human primary cell proliferation and anchorage-independent growth properties, similarly to E6 of HPV16, a high-risk HPV (HR-HPV). Interestingly, we demonstrate that, in contrast to E6 of HPV16, E6m corrupts neither p53 stability nor telomerase activity, but acts as a specific modulator of the transcriptional machinery. By studying E6m reversion mutants, we confirmed the importance of the second zinc-finger domain in triggering the observed upregulation of cell growth and of the transcriptional machinery. Reversion of these mutations in E6m (to yield strain E6r) fully abolished the oncogenic potential of E6m, transforming the phenotype of E6 from a high-risk to a low-risk phenotype. Importantly, our data define the importance of a cluster of mutations in the second zinc finger of E6m in increasing the oncogenic potential of HPV83.<\/jats:p>","DOI":"10.1099\/vir.0.032888-0","type":"journal-article","created":{"date-parts":[[2011,7,14]],"date-time":"2011-07-14T02:57:15Z","timestamp":1310612235000},"page":"2428-2436","source":"Crossref","is-referenced-by-count":2,"title":["Characterization of a cluster of oncogenic mutations in E6 of a human papillomavirus 83 variant isolated from a high-grade squamous intraepithelial lesion"],"prefix":"10.1099","volume":"92","author":[{"given":"Isabelle","family":"Cannavo","sequence":"first","affiliation":[{"name":"INSERM, U895, Centre M\u00e9diterran\u00e9en de M\u00e9decine Mol\u00e9culaire, C3M, Toxines Microbiennes dans la relation hote pathog\u00e8nes, Nice, France"},{"name":"Universit\u00e9 de Nice-Sophia-Antipolis, UFR M\u00e9decine, Nice, France"},{"name":"Laboratoire de Virologie, Centre Hospitalier Universitaire de Nice, H\u00f4pital Archet 2, Nice, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maxime","family":"Benchetrit","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Nice-Sophia-Antipolis, UFR M\u00e9decine, Nice, France"},{"name":"Laboratoire d\u2019Anatomo-Pathologie, Centre Hospitalier Universitaire de Nice, H\u00f4pital Archet 2, Nice, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9line","family":"Loubatier","sequence":"additional","affiliation":[{"name":"INSERM, U895, Centre M\u00e9diterran\u00e9en de M\u00e9decine Mol\u00e9culaire, C3M, Toxines Microbiennes dans la relation hote pathog\u00e8nes, Nice, France"},{"name":"Universit\u00e9 de Nice-Sophia-Antipolis, UFR M\u00e9decine, Nice, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory","family":"Michel","sequence":"additional","affiliation":[{"name":"INSERM, U895, Centre M\u00e9diterran\u00e9en de M\u00e9decine Mol\u00e9culaire, C3M, Toxines Microbiennes dans la relation hote pathog\u00e8nes, Nice, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuel","family":"Lemichez","sequence":"additional","affiliation":[{"name":"INSERM, U895, Centre M\u00e9diterran\u00e9en de M\u00e9decine Mol\u00e9culaire, C3M, Toxines Microbiennes dans la relation hote pathog\u00e8nes, Nice, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Val\u00e9rie","family":"Giordanengo","sequence":"additional","affiliation":[{"name":"INSERM, U895, Centre M\u00e9diterran\u00e9en de M\u00e9decine Mol\u00e9culaire, C3M, Toxines Microbiennes dans la relation hote pathog\u00e8nes, Nice, France"},{"name":"Universit\u00e9 de Nice-Sophia-Antipolis, UFR M\u00e9decine, Nice, France"},{"name":"Laboratoire de Virologie, Centre Hospitalier Universitaire de Nice, H\u00f4pital Archet 2, Nice, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"345","reference":[{"key":"r1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2006.12.013"},{"key":"r2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.20978"},{"key":"r3","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2006.08.038"},{"key":"r4","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1999.9822"},{"key":"r5","doi-asserted-by":"publisher","DOI":"10.1097\/00007435-200212000-00005"},{"key":"r6","doi-asserted-by":"publisher","DOI":"10.1078\/0171-9335-00213"},{"key":"r7","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2007.12.020"},{"key":"r8","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1128\/JVI.66.5.2814-2820.1992","article-title":"A second origin of DNA plus-strand synthesis is required for optimal human immunodeficiency virus replication","volume":"66","author":"Charneau","year":"1992","journal-title":"J Virol"},{"key":"r9","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1128\/JVI.68.2.1179-1185.1994","article-title":"Fusion from without directed by human immunodeficiency virus particles","volume":"68","author":"Clavel","year":"1994","journal-title":"J Virol"},{"key":"r10","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2007.06.029"},{"key":"r11","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90529-8"},{"key":"r12","doi-asserted-by":"publisher","DOI":"10.1086\/340125"},{"key":"r13","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24075"},{"key":"r14","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1128\/JVI.66.1.325-333.1992","article-title":"Transcriptional activation of several heterologous promoters by the E6 protein of human papillomavirus type 16","volume":"66","author":"Desaintes","year":"1992","journal-title":"J Virol"},{"key":"r15","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2004.03.033"},{"key":"r16","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)02041-7"},{"key":"r17","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205081"},{"key":"r18","doi-asserted-by":"publisher","DOI":"10.1016\/S0042-6822(03)00390-8"},{"key":"r19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200113200"},{"key":"r20","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1214704"},{"key":"r21","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-05-0864"},{"key":"r22","doi-asserted-by":"crossref","first-page":"3905","DOI":"10.1002\/j.1460-2075.1989.tb08570.x","article-title":"HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes","volume":"8","author":"Hawley-Nelson","year":"1989","journal-title":"EMBO J"},{"key":"r23","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgg085"},{"key":"r24","first-page":"199","article-title":"Molecular mechanisms of transformation by the human papillomaviruses","volume":"20","author":"Howley","year":"1989","journal-title":"Princess Takamatsu Symp"},{"key":"r25","doi-asserted-by":"crossref","first-page":"4129","DOI":"10.1002\/j.1460-2075.1991.tb04990.x","article-title":"A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18","volume":"10","author":"Huibregtse","year":"1991","journal-title":"EMBO J"},{"key":"r26","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02007-06"},{"key":"r27","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02556-08"},{"key":"r28","doi-asserted-by":"crossref","first-page":"4509","DOI":"10.1128\/JVI.70.7.4509-4516.1996","article-title":"High-risk human papillomavirus E6 protein has two distinct binding sites within p53, of which only one determines degradation","volume":"70","author":"Li","year":"1996","journal-title":"J Virol"},{"key":"r29","doi-asserted-by":"crossref","first-page":"7297","DOI":"10.1128\/JVI.73.9.7297-7307.1999","article-title":"Multiple functions of human papillomavirus type 16 E6 contribute to the immortalization of mammary epithelial cells","volume":"73","author":"Liu","year":"1999","journal-title":"J Virol"},{"key":"r30","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410343200"},{"key":"r31","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01318-08"},{"key":"r32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906357106"},{"key":"r33","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203817"},{"key":"r34","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204869"},{"key":"r35","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2009.06.008"},{"key":"r36","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-8-112"},{"key":"r37","first-page":"980","article-title":"Improved retroviral vectors for gene transfer and expression","volume":"7","author":"Miller","year":"1989","journal-title":"Biotechniques"},{"key":"r38","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2886"},{"key":"r39","doi-asserted-by":"crossref","first-page":"4417","DOI":"10.1128\/JVI.63.10.4417-4421.1989","article-title":"The E6 and E7 genes of the human papillomavirus type 16 together are necessary and sufficient for transformation of primary human keratinocytes","volume":"63","author":"M\u00fcnger","year":"1989","journal-title":"J Virol"},{"key":"r40","doi-asserted-by":"publisher","DOI":"10.1016\/S1386-6532(00)00125-6"},{"key":"r41","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021641"},{"key":"r42","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1995.1511"},{"key":"r43","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.93"},{"key":"r44","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.13.2061"},{"key":"r45","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90409-8"},{"key":"r46","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.13.5523"},{"key":"r47","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90384-3"},{"key":"r48","doi-asserted-by":"publisher","DOI":"10.1038\/314111a0"},{"key":"r49","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2001.1263"},{"key":"r50","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.20472"},{"key":"r51","first-page":"653","article-title":"Conditional immortalization of primary cells by human papillomavirus type 18 E6 and EJ-ras defines an E6 activity in G0\/G1 phase which can be substituted for mutations in p53","volume":"11","author":"Storey","year":"1995","journal-title":"Oncogene"},{"key":"r52","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.9.4467-4472.2001"},{"key":"r53","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1435900100"},{"key":"r54","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1128\/JVI.63.2.965-969.1989","article-title":"Human papillomavirus type 16 transformation of primary human embryonic fibroblasts requires expression of open reading frames E6 and E7","volume":"63","author":"Watanabe","year":"1989","journal-title":"J Virol"},{"key":"r55","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gng003"},{"key":"r56","doi-asserted-by":"publisher","DOI":"10.1126\/science.2157286"},{"key":"r57","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.81649-0"},{"key":"r58","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.605"},{"key":"r59","first-page":"829","article-title":"Human papillomavirus 16 E6 variants are more prevalent in invasive cervical carcinoma than the prototype","volume":"58","author":"Zehbe","year":"1998","journal-title":"Cancer Res"},{"key":"r60","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2008.09.036"},{"key":"r61","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24706"}],"container-title":["Journal of General Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/vir.0.032888-0?crawler=true","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T03:13:40Z","timestamp":1603422820000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/vir.0.032888-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,10,1]]},"references-count":61,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2011,10,1]]}},"URL":"https:\/\/doi.org\/10.1099\/vir.0.032888-0","relation":{},"ISSN":["0022-1317","1465-2099"],"issn-type":[{"value":"0022-1317","type":"print"},{"value":"1465-2099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,10,1]]}}}