TRIM35 mediates protection against influenza infection by activating TRAF3 and degrading viral PB2

• DOI: 10.1007/s13238-020-00734-6
• Publication Date: 2020-06-19T06:02:36Z
• Authors: Nan Sun; Li Jiang; Miaomiao Ye; Yihan Wang; Guangwen Wang; Xiaopeng Wan; Yuhui Zhao; Xia Wen; Libin Liang; Shujie Ma; Liling Liu; Zhigao Bu; Hualan Chen; Chengjun Li
• Keywords: RIG-I

Abstract Tripartite motif (TRIM) family proteins are important effectors of innate immunity against viral infections. Here we identified TRIM35 as a regulator TRAF3 activation. Deficiency in or inhibition suppressed the production type I interferon (IFN) response to infection. Trim35 -deficient mice were more susceptible influenza A virus (IAV) infection than wild-type mice. promoted RIG-I-mediated signaling by catalyzing Lys63-linked polyubiquitination and subsequent formation complex with VISA TBK1. IAV PB2 polymerase countered antiviral immune impeding activation TRAF3. mediated Lys48-linked proteasomal degradation PB2, thereby antagonizing its suppression Our vitro vivo findings thus reveal novel roles TRIM35, through Lys63- polyubiquitination, RIG-I mechanism defense