HUMAN-PAPILLOMAVIRUS-16 E6 ONCOPROTEIN BINDS TO INTERFERON REGULATORYFACTOR-3 AND INHIBITS ITS TRANSCRIPTIONAL ACTIVITY

Interferon regulatory factor-3 (IRF-3) was found to specifically inter act 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 st able complex with other transcriptional regulators that bind to the re gulatory elements of the IFN beta promoter. We show that IRF-3 is a po tent transcriptional activator and demonstrate that HPV16 E6 can inhib it its transactivation function. The expression of HPV16 E6 in primary human keratinocytes inhibits the induction of IFN beta mRNA following Sendai virus infection. The binding of HPV16 E6 to IRF-3 does not res ult in its ubiquitination or degradation. We propose that the interact ion of E6 with IRF-3 and the inhibition of IRF-3's transcriptional act ivity may provide the virus a means to circumvent the normal antiviral response of an HPV16-infected cell.