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

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-?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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Cell Line, Disease Models, Animal, HEK293 Cells, HeLa Cells, Humans, Immunity, Innate, Interferon Regulatory Factor-3, Mice, Microtubule-Associated Proteins, Mitochondria, Protein Multimerization, Protein-Serine-Threonine Kinases, TNF Receptor-Associated Factor 3, Virus Diseases
EMBO J.
Date: Dec. 16, 2018
Download Curated Data For This Publication
222356
Switch View:
  • Interactions 9