Avian Reovirus A Protein Inhibits Type I Interferon Production by Abrogating Interferon Regulatory Factor 7 Activation

Type I interferon (IFN) response is the first line of host-based innate immune defense against viral infections. However, viruses have developed multiple strategies to counter host IFN responses, so they may continue infecting hosts via effective replication. Avian reovirus (ARV), an RNA virus, causes viral arthritis or tenosynovitis in chickens. Previous studies have shown that ARV is highly resistant to the antiviral effects of IFN. However, the underlying mechanisms that enable ARV to block the IFN pathway remain unclear. In this study, we found that ectopic expression of ARV protein, sigma A, significantly inhibited the production of IFN-beta induced by melanoma-differentiation-associated gene 5 (MDA5) and poly(I center dot C). Knockdown of sigma A during ARV infection enhances the IFN-beta response and suppresses viral replication. ARV sigma A inhibited the MDA5-mediated IFN-beta activation by targeting interferon regulatory factor 7 (IRF7). Further studies demonstrated that sigma A interacts with IRF7, thereby blocking IRF7 dimerization and nuclear translocation, finally leading to the inhibition of IFN-beta production. These findings reveal a novel mechanism that allows ARV to evade host antiviral immunity. IMPORTANCE ARV, the causative agent of viral arthritis or tenosynovitis in chickens, has a significant economic impact as it results in poor weight gain and increased feed conversion ratios. The MDA5-mediated IFN-beta signal pathway plays an important role in host antiviral defense. Therefore, RNA viruses have developed mechanisms to counter this signaling pathway and successfully establish infection. However, the strategies adopted by ARV to block MDA5-IRF7 signaling remain unclear. In the current study, we demonstrated that ARV sigma A inhibits this pathway by binding to IRF7, which blocked IRF7 dimerization and nuclear translocation. Our findings may provide insights into how avian reovirus counteracts the innate antiviral immunity of the host to ensure viral replication.