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

• 作者: 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
• 来源期刊: 蛋白质与细胞
• 年，卷（期）: 2020,（12）
• 所属期刊栏目: RESEARCH ARTICLE
• 页码范围: 894-914
• 页数: 21页
• 语种: 英文

摘要

Tripartite motif(TRIM)family proteins are important effectors of Innate immunity against viral infections.Here we identified TRIM35 as a regulator of TRAF3 activation.Deficiency in or inhibition of TRIM35 sup-pressed the production of type Ⅰ Interferon(IFN)In response to viral infection.Trlm35-deficient mice were more susceptible to influenza A virus(IAV)infection than were wild-type mice.TRIM35 promoted the RIG-I-mediated signaling by catalyzing Lys63-linked polyu-biquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1.IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitina-tion and activation of TRAF3.TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2,thereby antagonizing its suppression of TRAF3 activation.Our In vitro and in vivo findings thus reveal novel roles of TRIM35,through catalyzing Lys63-or Lys48-Ilnked polyubiquitination,in RIG-I antiviral immunity and mechanism of defense against IAV infection.