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The Human papillomavirus type 16 E7 oncoprotein induces a transcriptional repressor complex on the Toll-like receptor 9 promoter

Hasan, Uzma A.
Zannetti, Claudia
Parroche, Peggy
Goutagny, Nadège
Malfroy, Marine
Roblot, Guillaume
Carreira, Christine
Hussain, Ishraq
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Published in The Journal of experimental medicine. 2013, vol. 210, no. 7, p. 1369-87
Abstract 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-κBp50-p65 and ERα 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-κB and ERα 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.
Keywords Base SequenceCell Line, TumorCervix Uteri/immunology/metabolism/virologyDown-Regulation/geneticsEpithelial Cells/immunology/metabolism/virologyFemaleHEK293 CellsHeLa CellsHost-Pathogen Interactions/genetics/immunologyHuman papillomavirus 16/immunology/pathogenicityHumansMolecular Sequence DataPapillomavirus E7 Proteins/immunologyPapillomavirus Infections/genetics/immunology/virologyPromoter Regions, GeneticRepressor Proteins/metabolismToll-Like Receptor 9/genetics
PMID: 23752229
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Research group Groupe Picard
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HASAN, Uzma A. et al. The Human papillomavirus type 16 E7 oncoprotein induces a transcriptional repressor complex on the Toll-like receptor 9 promoter. In: The Journal of experimental medicine, 2013, vol. 210, n° 7, p. 1369-87. doi: 10.1084/jem.20122394 https://archive-ouverte.unige.ch/unige:30766

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Deposited on : 2013-10-28

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