数字农科院2.0

Foot-and-mouth disease virus structural protein VP3 degrades Janus kinase 1 to inhibit IFN-gamma signal transduction pathways

文献类型： 外文期刊

作者： Li, Dan;Yang, Fan;Liu, Hua-Nan;Zhu, Zi-Xiang;Cao, Wei-Jun;Liu, Xiang-Tao;Zheng, Hai-Xue;Wei, Jin;Li, Shu;Shu, Hong-Bing

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关键词： Foot-and-mouth disease virus;IFN-;signaling pathway;janus kinase 1;structural protein VP3

期刊名称： CELL CYCLE

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收录情况： SCI

摘要： Foot-and-mouth disease is a highly contagious viral disease of cloven-hoofed animals that is caused by foot-and-mouth disease virus (FMDV). To replicate efficiently in vivo, FMDV has evolved methods to circumvent host antiviral defense mechanisms, including those induced by interferons (IFNs). Previous research has focused on the effect of FMDV L-pro and 3C(pro) on type I IFNs. In this study, FMDV VP3 was found to inhibit type II IFN signaling pathways. The overexpression of FMDV VP3 inhibited the IFN--triggered phosphorylation of STAT1 at Tyr701 and the subsequent expression of downstream genes. Mechanistically, FMDV VP3 interacted with JAK1/2 and inhibited the tyrosine phosphorylation, dimerization and nuclear accumulation of STAT1. FMDV VP3 also disrupted the assembly of the JAK1 complex and degraded JAK1 but not JAK2 via a lysosomal pathway. Taken together, the results reveal a novel mechanism used by which FMDV VP3 counteracts the type II IFN signaling pathways.

分类号： Q2

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