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Research Article: The APC/C subunit APC7 exerts antiviral effects by targeting the adaptor protein MAVS

Date Published: 2026-08-11

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.

Introduction:
The innate immune system recognizes invading pathogens through pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), cytoplasmic DNA sensors, and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) ( 1 , 2 ). Upon binding to cytoplasmic viral RNA, RIG-I undergoes conformational changes and recruits mitochondrial antiviral signaling protein (MAVS) ( 3 , 4 ). Activation of MAVS induces the formation of prion-like aggregates on mitochondria ( 5 , 6 ). Subsequently, MAVS activates TBK1 and…

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