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A20 is a potent inhibitor of TLR3‐ and Sendai virus‐induced activation of NF‐κB and ISRE and IFN‐β promoter
Author(s) -
Wang Yan-Yi,
Li Lianyun,
Han Ke-Jun,
Zhai Zhonghe,
Shu Hong-Bing
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.08.071
Subject(s) - trif , sendai virus , tlr3 , transcription factor , interferon regulatory factors , promoter , interferon , signal transduction , microbiology and biotechnology , biology , chemistry , toll like receptor , innate immune system , receptor , virology , virus , gene expression , gene , biochemistry
Toll‐like receptor 3 (TLR3) recognizes dsRNA generated during viral infection and activation of TLR3 results in induction of type I interferons (IFNs) and cellular anti‐viral response. TLR3 is associated with a TIR domain‐containing adapter protein TRIF, which activates distinct downstream pathways leading to activation of NF‐κB and ISRE sites in the promoters of type I IFNs. We show here that A20, a NF‐κB‐inducible zinc finger protein that has been demonstrated to be an inhibitor of TNF‐induced NF‐κB activation and a physiological suppressor of inflammatory response, potently inhibited TLR3‐ and Sendai virus‐mediated activation of ISRE and NF‐κB and IFN‐β promoter in reporter gene assays. A20 also inhibited TRIF‐, but not its downstream signaling components TBK1‐, IKKβ‐, and IKKε‐mediated activation of ISRE and NF‐κB and IFN‐β promoter. Moreover, A20 interacted with TRIF in co‐immunoprecipitation experiments. Finally, expression of A20 could be induced at protein level by Sendai virus infection. These data suggest that A20 targets TRIF to inhibit TLR3‐mediated induction of IFN‐β transcription and functions as a feedback negative regulator for TLR3 signaling and cellular anti‐viral response.