The APC/C subunit APC7 exerts antiviral effects by targeting the adaptor protein MAVS
TL;DR
It is 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.
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.