TARBP2 negatively regulates IFN-β production and innate antiviral response by targeting MAVS

Abstract MAVS as an essential receptor protein for anti-virus innate immunity plays an important role in the production of virus-induced typeⅠ interferon and regulation of interferon regulatory factor 3/7. Understanding the MAVS-mediated antiviral signaling pathway can provide detailed insights. In this study, we identify transactivation response element RNA-binding protein (TARBP2), as an inhibitor of the cellular protein kinase PKR, negatively regulates virus -induced IFN-β production by targets MAVS. Overexpression of TARBP2 inhibits virus-induced IFN-β production as well as cellular antiviral response. Then knockdown of TARBP2 inhibited virus-induced IFN-β signaling. Further studies demonstrated that TARBP2 interacted with MAVS and targeted MAVS to abrogate MAVS-RIG-I and MAVS-TRAF3 association. Our findings suggest that TARBP2 is an important non-redundant virus-mediated negative regulator of typeⅠ interferon.