2. Academic Validation
  3. TRAF3IP3 mediates the recruitment of TRAF3 to MAVS for antiviral innate immunity

TRAF3IP3 mediates the recruitment of TRAF3 to MAVS for antiviral innate immunity

  • EMBO J. 2019 Sep 16;38(18):e102075. doi: 10.15252/embj.2019102075.
Wenting Zhu 1,  Jiaxin Li 1,  Rui Zhang 1,  Yixiang Cai 1,  Changwan Wang 1,  Shishi Qi 1,  She Chen 2,  Xiaozhen Liang 3,  Nan Qi 1 4,  Fajian Hou 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • 2 National Institute of Biological Sciences, Beijing, China.
  • 3 Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
  • 4 Institute of Engineering Biology and Health, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang, China.
PMID: 31390091 DOI: 10.15252/embj.2019102075
Abstract

RIG-I-MAVS Antiviral signaling represents an important pathway to stimulate interferon production and confer innate immunity to the host. Upon binding to viral RNA and Riplet-mediated polyubiquitination, RIG-I promotes prion-like aggregation and activation of MAVS. MAVS subsequently induces interferon production by activating two signaling pathways mediated by TBK1-IRF3 and IKK-NF-κB respectively. However, the mechanism underlying the activation of MAVS downstream pathways remains elusive. Here, we demonstrated that activation of TBK1-IRF3 by MAVS-Region III depends on its multimerization state and identified TRAF3IP3 as a critical regulator for the downstream signaling. In response to virus Infection, TRAF3IP3 is accumulated on mitochondria and thereby facilitates the recruitment of TRAF3 to MAVS for TBK1-IRF3 activation. Traf3ip3-deficient mice demonstrated a severely compromised potential to induce interferon production and were vulnerable to RNA virus Infection. Our findings uncover that TRAF3IP3 is an important regulator for RIG-I-MAVS signaling, which bridges MAVS and TRAF3 for an effective Antiviral innate immune response.

Keywords

MAVS; RIG-I; TRAF3IP3; innate immunity; interferon.

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