Human papillomavirus type-16 (HPV-16) major transforming proteins functionally interact with interferon signaling mechanisms

Abstract Since the IFN system has been implicated in cell growth and differentiation control mechanisms, we evaluated the influence of the expression of HPV-16 E6 and E7 oncoproteins on IFN signaling by using cotransfection experiments. Both viral oncoproteins differentially interfered with the inducibility of IFN-beta promoter by Sendai virus. The activation by IFN-gamma of a GBP ISRE reporter was dramatically affected by both viral proteins suggesting a disruption of STATs/IRFs function. Further, the inducibility of 6-16 gene ISRE reporter by IFN-alpha was decreased to varying degrees by both viral oncoproteins, implying that ISGF3 function is also impaired. Taken together, these observations suggest that HPV-16 negatively interacts with cellular targets of the IFN system, and these interactions may be implicated in cellular transformation caused by HPVs and their refractory response to IFN treatment.