2. Academic Validation
  3. TRIM35 mediates protection against influenza infection by activating TRAF3 and degrading viral PB2

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

  • Protein Cell. 2020 Dec;11(12):894-914. doi: 10.1007/s13238-020-00734-6.
Nan Sun 1,  Li Jiang 1,  Miaomiao Ye 1,  Yihan Wang 1,  Guangwen Wang 1,  Xiaopeng Wan 1,  Yuhui Zhao 1,  Xia Wen 1,  Libin Liang 1,  Shujie Ma 1,  Liling Liu 1,  Zhigao Bu 1,  Hualan Chen 2,  Chengjun Li 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150069, China.
  • 2 State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150069, China. chenhualan@caas.cn.
  • 3 State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150069, China. lichengjun@caas.cn.
PMID: 32562145 DOI: 10.1007/s13238-020-00734-6
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-I-mediated 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

PB2; TRAF3; TRIM35; antiviral immunity; influenza A virus; ubiquitination.

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