{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:28:57Z","timestamp":1792121337214,"version":"4.4.0"},"reference-count":85,"publisher":"Rockefeller University Press","issue":"7","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,7,1]]},"abstract":"<jats:p>Human papillomavirus type 16 (HPV16) and other oncogenic viruses have been reported to deregulate immunity by suppressing the function of the double-stranded DNA innate sensor TLR9. However, the mechanisms leading to these events remain to be elucidated. We show that infection of human epithelial cells with HPV16 promotes the formation of an inhibitory transcriptional complex containing NF-\u03baBp50\u2013p65 and ER\u03b1 induced by the E7 oncoprotein. The E7-mediated transcriptional complex also recruited the histone demethylase JARID1B and histone deacetylase HDAC1. The entire complex bound to a specific region on the TLR9 promoter, which resulted in decreased methylation and acetylation of histones upstream of the TLR9 transcriptional start site. The involvement of NF-\u03baB and ER\u03b1 in the TLR9 down-regulation by HPV16 E7 was fully confirmed in cervical tissues from human patients. Importantly, we present evidence that the HPV16-induced TLR9 down-regulation affects the interferon response which negatively regulates viral infection. Our studies highlight a novel HPV16-mediated mechanism that combines epigenetic and transcriptional events to suppress a key innate immune sensor.<\/jats:p>","DOI":"10.1084\/jem.20122394","type":"journal-article","created":{"date-parts":[[2013,6,11]],"date-time":"2013-06-11T02:45:21Z","timestamp":1370918721000},"page":"1369-1387","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":190,"title":["The Human papillomavirus type 16 E7 oncoprotein induces a transcriptional repressor complex on the Toll-like receptor 9 promoter"],"prefix":"10.1084","volume":"210","author":[{"given":"Uzma A.","family":"Hasan","sequence":"first","affiliation":[{"name":"Infections and Cancer Biology Group, International Agency for Research on Cancer, Lyon 69008, France 1"},{"name":"CIRI, Oncoviruses and Innate Immunity, INSERM U1111, Ecole Normale Sup\u00e9rieure, Universit\u00e9 de Lyon, CNRS-UMR5308, Hospices Civils de Lyon, Lyon 69000, France 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Zannetti","sequence":"additional","affiliation":[{"name":"CIRI, Oncoviruses and Innate Immunity, INSERM U1111, Ecole Normale Sup\u00e9rieure, Universit\u00e9 de Lyon, CNRS-UMR5308, Hospices Civils de Lyon, Lyon 69000, France 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Parroche","sequence":"additional","affiliation":[{"name":"CIRI, Oncoviruses and Innate Immunity, INSERM U1111, Ecole Normale Sup\u00e9rieure, Universit\u00e9 de Lyon, CNRS-UMR5308, Hospices Civils de Lyon, Lyon 69000, France 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nad\u00e8ge","family":"Goutagny","sequence":"additional","affiliation":[{"name":"CRCL, UMR INSERM 1052 - CNRS 5286, Centre L\u00e9on B\u00e9rard, Lyon 69008, France 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Malfroy","sequence":"additional","affiliation":[{"name":"CRCL, UMR INSERM 1052 - CNRS 5286, Centre L\u00e9on B\u00e9rard, Lyon 69008, France 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Roblot","sequence":"additional","affiliation":[{"name":"CIRI, Oncoviruses and Innate Immunity, INSERM U1111, Ecole Normale Sup\u00e9rieure, Universit\u00e9 de Lyon, CNRS-UMR5308, Hospices Civils de Lyon, Lyon 69000, France 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Carreira","sequence":"additional","affiliation":[{"name":"Infections and Cancer Biology Group, International Agency for Research on Cancer, Lyon 69008, France 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishraq","family":"Hussain","sequence":"additional","affiliation":[{"name":"Division of Veterinary Biochemistry FVSc & AH, SK Alusteng, Kashmir 190006, India 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Programme of Infection & Cancer, DKFZ, Heidelberg 69120, Germany 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"Taylor-Papadimitriou","sequence":"additional","affiliation":[{"name":"Breast Cancer Biology Group, King\u2019s College London School of Medicine, Thomas Guy House, Guy\u2019s Hospital, London SE1 9RT, England, UK 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Picard","sequence":"additional","affiliation":[{"name":"University of Geneva, 1211 Gen\u00e8ve 4, Switzerland 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bakary S.","family":"Sylla","sequence":"additional","affiliation":[{"name":"Infections and Cancer Biology Group, International Agency for Research on Cancer, Lyon 69008, France 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Trinchieri","sequence":"additional","affiliation":[{"name":"Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702 8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruslan","family":"Medzhitov","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine, New Haven, CT 06510 9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Tommasino","sequence":"additional","affiliation":[{"name":"Infections and Cancer Biology Group, International Agency for Research on Cancer, Lyon 69008, France 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2013,6,10]]},"reference":[{"key":"2023072601523507700_bib1","doi-asserted-by":"publisher","first-page":"2210","DOI":"10.1128\/MCB.00964-10","article-title":"IkappaB kinase beta promotes cell survival by antagonizing p53 functions through DeltaNp73alpha phosphorylation and stabilization","volume":"31","author":"Accardi","year":"2011","journal-title":"Mol. 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