Porcine reproductive and respiratory syndrome virus Nsp4 cleaves ZAP to antagonize its antiviral activity

文献类型： 外文期刊

第一作者： Zhao, Yongxiang

作者： Zhao, Yongxiang;Song, Zhongbao;Bai, Juan;Liu, Xuewei;Jiang, Ping;Zhao, Yongxiang;Nauwynck, Hans;Jiang, Ping;Song, Zhongbao

作者机构：

关键词： PRRSV; Nsp4; Antagonize; ZAP; Antiviral activity

期刊名称：VETERINARY MICROBIOLOGY （ 影响因子：3.293； 五年影响因子：3.599 ）

ISSN： 0378-1135

年卷期： 2020 年 250 卷

页码：

收录情况： SCI

摘要： Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important pathogens impacting the global swine industry. PRRSV has been recognized to modulate the host immune response through a number of mechanisms. In our previous study, we found that over-expression of ZAP, a zinc finger antiviral protein of host, could suppress PRRSV replication, but how PRRSV escape the restriction of ZAP under natural conditions was still unknown. In this study, We found PRRSV infection significantly down-regulate the endogenous ZAP protein expression in Marc-145 cells. And PRRSV nonstructural protein 4 (Nsp4), a 3C-like serine proteinase, was screened to be responsible for ZAP reduction. Nsp4 could cleave ZAP, depending on its protease activity. The anti-PRRSV activity of ZAP was antagonized by Nsp4 in Marc-145 cells. In addition, we identified a unique amino acid, serine 180 of Nsp4 was required for efficient degradation of ZAP, and the mutation at residue 180 could decrease the ability of recombinant PRRSV to degrade ZAP. Those findings reveal a manner of PRRSV Nsp4 antagonizing the antiviral activity of ZAP, and shed light on a new strategy evolved by PRRSV to escape the host defense.

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