The Foot-and-Mouth Disease Virus Lb Protease Cleaves Intracellular Transcription Factors STAT1 and STAT2 to Antagonize IFN-13-Induced Signaling

文献类型： 外文期刊

第一作者： Ma, XuSheng

作者： Ma, XuSheng;Luo, ZhiKuan;Song, Rui;Nian, XiaoFeng;Choudhury, Sk Mohiuddin;Ru, Yi;Yang, Fan;Zeng, ZongBo;Cao, WeiJun;Pei, JingJing;Liu, XiangTao;Zheng, HaiXue;Ma, XuSheng;Yang, Fan;Cao, WeiJun;Pei, JingJing;Liu, XiangTao;Zheng, HaiXue;Zhang, YuXia;Zheng, HaiXue;Zhang, YuXia;Zheng, HaiXue;Zheng, HaiXue

作者机构：

期刊名称：JOURNAL OF IMMUNOLOGY （ 影响因子：4.4； 五年影响因子：5.2 ）

ISSN： 0022-1767

年卷期： 2023 年 210 卷 3 期

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收录情况： SCI

摘要： Foot-and-mouth disease virus (FMDV) is the causative agent of foot-and-mouth disease, one of the most highly infectious animal viruses throughout the world. The JAK-STAT signaling pathway is a highly conserved pathway for IFN-13-induced antiviral gene expression. Previous studies have shown that FMDV can strongly suppress the innate immune response. Moreover, although STAT1 and STAT2 (STAT1/2) have been well established in JAK-STAT signaling -induced antiviral gene expression, whether FMDV proteins inhibit IFN-13-induced JAK-STAT signaling remains poorly understood. In this study, we described the Lb leader protease (Lbpro) of FMDV as a candidate for inhibiting IFN-13-induced signaling transduction via directly interacting with STAT1/2. We further showed that Lbpro colocalized with STAT1/2 to inhibit their nuclear translocation. Importantly, Lbpro cleaved STAT1/2 to inhibit IFN-13-induced signal transduction, whereas the catalytically inactive mutant of LC51A (Lbpro with cysteine substituted with alanine at amino acid residue 51) had no effect on the stability of STAT1/2 proteins. The cleavage of the STAT1/2 proteins was also determined during FMDV infection in vitro. Lbpro could cleave the residues between 252 and 502 aa for STAT1 and the site spanning residues 140 -150 aa (QQHEIESRIL) for STAT2. The in vivo results showed that Lbpro can cleave STAT1/2 in pigs. Overall, our findings suggest that FMDV Lbpro-mediated targeting of STAT1/2 may reveal a novel mechanism for viral immune evasion.

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