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

Cell Cycle
Dan LiHong-Bing Shu

Abstract

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-γ-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.

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Citations

Jun 16, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Huisheng LiuHaixue Zheng
Aug 9, 2020·European Journal of Immunology·Xiangle ZhangHaixue Zheng
Jul 1, 2017·Frontiers in Cellular and Infection Microbiology·Miguel Rodríguez Pulido, Margarita Sáiz
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Nov 10, 2020·Frontiers in Microbiology·Jiangling PengDan Li
Mar 16, 2021·Frontiers in Immunology·Kangli LiHaixue Zheng

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Methods Mentioned

BETA
nuclear translocation
GTPase
co-immunoprecipitation
transfection
PCR
electrophoresis

Software Mentioned

SPSS17
Image J

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