High-Risk Mucosal Human Papillomavirus 16 (HPV16) E6 Protein and Cutaneous HPV5 and HPV8 E6 Proteins Employ Distinct Strategies To Interfere with Interferon Regulatory Factor 3-Mediated Beta Interferon Expression
Juline Poirson, Irina P. Suárez, Marie‐Laure Straub, A. Cousido-Siah, Paul Peixoto, Éric Hervouet, Anne L. Foster, A. Mitschler, Noella Mukobo, Yassmine Chebaro, Dominique Garcin, Sevda Recberlik, Christian Gaiddon, Danièle Altschuh, Yves Nominé, A. Podjarny, Gilles Travé, Murielle Masson
Abstract
Persistent HPV infections can be associated with the development of several cancers. The ability to persist depends on the ability of the virus to escape the host immune system. The type I interferon (IFN) system is the first-line antiviral defense strategy. HPVs carry early proteins that can block the activation of IFN-I. Among mucosal α-genus HPV types, the HPV16 E6 protein has a remarkable property to strongly interact with the transcription factor IRF3. Instead, cutaneous HPV5 and HPV8 E6 proteins bind to the IRF3 cofactor CBP. These results highlight the versatility of E6 proteins to interact with different cellular targets. The interaction between the HPV16 E6 protein and IRF3 might contribute to the higher prevalence of HPV16 than that of other high-risk mucosal HPV types in HPV-associated cancers.