期刊
EMBO JOURNAL
卷 38, 期 18, 页码 -出版社
WILEY
DOI: 10.15252/embj.2019102075
关键词
innate immunity; interferon; MAVS; RIG-I; TRAF3IP3
资金
- National Natural Science Foundation of China [91754117, 31671471]
- National Science Foundation for Young Scientists of China [31600700]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB19000000]
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-kappa B 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.
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