PMID:28487378

Citation	Huang, L, Xiong, T, Yu, H, Zhang, Q, Zhang, K, Li, C, Hu, L, Zhang, Y, Zhang, L, Liu, Q, Wang, S, He, X, Bu, Z, Cai, X, Cui, S, Li, J and Weng, C (2017) Encephalomyocarditis virus 3C protease attenuates type I interferon production through disrupting the TANK-TBK1-IKKε-IRF3 complex. Biochem. J. 474:2051-2065
Abstract	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.
Links	PubMed PMC5465970 Online version:10.1042/BCJ20161037
Keywords	Adaptor Proteins, Signal Transducing/antagonists & inhibitors; Adaptor Proteins, Signal Transducing/chemistry; Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/metabolism; Amino Acid Substitution; Animals; Cell Line; Cysteine Endopeptidases/chemistry; Cysteine Endopeptidases/genetics; Cysteine Endopeptidases/metabolism; Dogs; Encephalomyocarditis virus/enzymology; Gene Deletion; Humans; I-kappa B Kinase/antagonists & inhibitors; I-kappa B Kinase/chemistry; I-kappa B Kinase/genetics; I-kappa B Kinase/metabolism; Interferon Regulatory Factor-3/antagonists & inhibitors; Interferon Regulatory Factor-3/chemistry; Interferon Regulatory Factor-3/genetics; Interferon Regulatory Factor-3/metabolism; Interferon Type I/antagonists & inhibitors; Interferon Type I/biosynthesis; Mesocricetus; Mutagenesis, Site-Directed; Mutation; Peptide Fragments/antagonists & inhibitors; Peptide Fragments/chemistry; Peptide Fragments/genetics; Peptide Fragments/metabolism; Phosphorylation; Protein Multimerization; Protein Processing, Post-Translational; Protein-Serine-Threonine Kinases/antagonists & inhibitors; Protein-Serine-Threonine Kinases/chemistry; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism; Proteolysis; Recombinant Fusion Proteins/chemistry; Recombinant Fusion Proteins/metabolism; Viral Proteins/chemistry; Viral Proteins/genetics; Viral Proteins/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
EMCV:POLG	involved_in	GO:0039503: suppression by virus of host innate immune response	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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