Li Huang, Tao Xiong, Huibin Yu, Quan Zhang, Kunli Zhang, Changyao Li, Liang Hu,Yuanfeng Zhang, Lijie Zhang, Qinfang Liu, Shengnan Wang, Xijun He, Zhigao Bu, Xuehui Cai,Shangjin Cui, Jiangnan Li, Changjiang Weng

Biochemical Journal May 09, 2017,BCJ20161037

Abstract

TRAF family member-associated NF-κB activator (TANK) is a scaffold protein that assembles into the interferon regulator factor 3 (IRF3)-phosphorylating TBK1-IKKε complex, where it is involved in regulating phosphorylation of the IRF3 and interferon (IFN) production. However, the functions of TANK in Encephalomyocarditis virus (EMCV) infection-induced type I IFN production are not fully understood. Here, we demonstrated that, instead of stimulating type I IFN production, the EMCV-HB10 strain infection potently inhibited Sendai virus (SeV)- and polyI:C-induced IRF3 phosphorylation and type I IFN production in HEK293T cells. Mechanistically, EMCV 3C protease (EMCV 3C) cleaved TANK and disrupted the TANK-TBK1-IKKε-IRF3 complex, which resulted in the reduction of IRF3 phosphorylation and type I IFN production. Taken together, our findings demonstrate that EMCV adopts a novel strategy to evade host innate immune responses through cleavage of TANK.