Key result
EMCV 3C protease cleaves TANK and disrupts the TANK-TBK1-IKKε-IRF3 complex, potently inhibiting IRF3 phosphorylation and type I interferon production to evade host innate immune responses.
EMCV evades host innate immune responses by using its 3C protease to cleave TANK, thereby inhibiting type I interferon production.
May inform EMCV myocarditis models; leaves open whether 3C protease inhibition alters innate immunity or disease in vivo.
TRAF family member-associated NF-κB activator (TANK) is a scaffold protein that assembles into the interferon (IFN) regulator factor 3 (IRF3)-phosphorylating TANK-binding kinase 1 (TBK1)-(IκB) kinase ε (IKKε) complex, where it is involved in regulating phosphorylation of the IRF3 and 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- 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 in 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.
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Huang et al. (2017) studied Encephalomyocarditis virus (EMCV) infection. EMCV 3C protease was evaluated on IRF3 phosphorylation and type I IFN production. EMCV 3C protease cleaves TANK and disrupts the TANK-TBK1-IKKε-IRF3 complex, potently inhibiting IRF3 phosphorylation and type I interferon production to evade host innate immune responses.