title: Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity.
abstract: Interferon regulatory factor-3 (IRF-3) was found to specifically interact with HPV16 E6 in a yeast two-hybrid screen. IRF-3 is activated by the presence of double-stranded RNA or by virus infection to form a stable complex with other transcriptional regulators that bind to the regulatory elements of the IFNbeta promoter. We show that IRF-3 is a potent transcriptional activator and demonstrate that HPV16 E6 can inhibit its transactivation function. The expression of HPV16 E6 in primary human keratinocytes inhibits the induction of IFNbeta mRNA following Sendai virus infection. The binding of HPV16 E6 to IRF-3 does not result in its ubiquitination or degradation. We propose that the interaction of E6 with IRF-3 and the inhibition of IRF-3's transcriptional activity may provide the virus a means to circumvent the normal antiviral response of an HPV16-infected cell.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115 USA.
authors.forename: L V
authors.initials: LV
authors.lastname: Ronco
authors.forename: A Y
authors.initials: AY
authors.lastname: Karpova
authors.forename: M
authors.initials: M
authors.lastname: Vidal
authors.forename: P M
authors.initials: PM
authors.lastname: Howley
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D050838:Interferon Regulatory Factor-3; D016899:Interferon-beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D015603:Keratinocytes / Q000378:metabolism / Q000821:virology; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology*; D011485:Protein Binding / Q000235:genetics; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D012097:Repressor Proteins; D018108:Respirovirus / Q000502:physiology; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000502:physiology; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016899:Interferon-beta