A20 is a potent inhibitor of TLR3- and Sendai virus-induced activation of NF-κB and ISRE and IFN-β promoter

• Published in: FEBS letters 2004-10, Vol.576 (1), p.86-90
• Main Authors: Wang, Yan-Yi, Li, Lianyun, Han, Ke-Jun, Zhai, Zhonghe, Shu, Hong-Bing
• Format: Article
• Language: English
• Subjects: A20; IFN-β; Interferon-stimulated response element; NF-κB; Toll-like receptor 3
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2004.08.071

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.