Abstract

The innate immune response is the first line of host defense against viral infection. RNA virus infection triggers activation of retinoic acid-inducible gene-I (RIG-I)-mitochondrial antiviral signaling protein (MAVS) signaling pathway, resulting in the formation of prion-like aggregates of MAVS and production of type I interferons (IFN-I). Here, we found that APC7, a subunit of the anaphase-promoting complex/cyclosome (APC/C), can significantly restrict the replication of RNA viruses including Enterovirus 71 (EV71) and vesicular stomatitis virus (VSV). Further experiments showed that overexpression of APC7 enhances RNA virus-induced IFN-I expression, whereas knockdown of APC7 reduces it. Moreover, APC7 regulated the innate immune response independently of APC/C catalytic function. Subsequent analysis indicated that APC7 is partly localized to mitochondria, where it interacts with the transmembrane domain of MAVS. Furthermore, we discovered that APC7 promotes K63-linked polyubiquitination and mitochondrial aggregation of MAVS after RNA virus infection. Taken together, these findings demonstrated that APC7 potentiates the antiviral response through activation of MAVS-mediated signaling, which provides new insights into the regulatory mechanisms of innate immunity and viral infections.