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
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China
Funds: The work was supported by the National Key Research and Development Program of China (2016YFD0500205), the National Natural Science Foundation of China (NSFC) (Grant Nos. 31521005, 31672582, 31422054, and 31472215), the Natural Science Foundation of Heilongjiang Province (JQ2019C005), and by the Central Public-Interest Scientific Institution Basal Research Fund (No. Y2017JC35).
Received Date: 2020-04-08
Abstract
Abstract
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 suppressed the production of type I interferon (IFN) in response to viral infection. Trim35-deficient mice were more susceptible to influenza A virus (IAV) infection than were wild-type mice. TRIM35 promoted the RIG-Imediated signaling by catalyzing Lys63-linked polyubiquitination 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 polyubiquitination 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-linked polyubiquitination, in RIG-I antiviral immunity and mechanism of defense against IAV infection.Keywords: influenza A virus,
PB2,
TRIM35,
TRAF3,
ubiquitination,
antiviral immunity
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