The viral proteins of influenza A virus competitively bind to TRIM31 with MAVS to fine-tune the antiviral innate immunity

作者：Jiaxin Huang, Shuai Xu, Junwen Liu, Qian Wang, Lu Han, Mengyao Ji, Cao‐Qi Lei, Qiyun Zhu, Hualan Chen · 发表于：Journal of Virology · 年份：2025 · DOI：10.1128/jvi.01893-25 · 被引用次数：6 · 研究领域：interferon and immune responses、Influenza Virus Research Studies、Respiratory viral infections research

The influenza A virus (IAV) continues to pose a serious threat to animals and humans, making it urgent to reveal more about IAV-host interactions. Tripartite motif protein 31 (TRIM31), an E3 ubiquitin ligase, has been identified as an agonist of the type-I interferon (IFN-I) response against RNA viruses by targeting mitochondrial antiviral signaling protein (MAVS). Here, we demonstrated that TRIM31 plays critical and novel roles in the life cycle of IAV. TRIM31 promoted the IFN-I signaling induced by IAV; however, it was surprisingly found that TRIM31 does not affect IAV replication. Instead, IAV replication was significantly promoted by TRIM31 in MAVS- or interferon receptor-deficient cells, suggesting TRIM31 may facilitate IAV replication in an interferon-independent manner. Mechanistically, TRIM31 interacted specifically with the basic polymerase 1 (PB1), acidic polymerase (PA), and hemagglutinin (HA) proteins of different subtypes of IAV. The interaction between TRIM31 and the PB1, PA, and HA proteins enhances the stability and polymerase and membrane fusion activities of these viral proteins by catalyzing the K63-linked ubiquitination. Further, the PB1, PA, and HA proteins competitively bind to TRIM31 for IAV replication, leading to the attenuation of the TRIM31-MVAS complex-mediated IFN-I signaling activation. Therefore, the antiviral and proviral effects of TRIM31 reach a balance in IAV-infected cells, resulting in no significant impact on IAV replication. Our novel fi...