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Porcine reproductive and respiratory syndrome virus Nsp4 cleaves ZAP to antagonize its antiviral activity
Veterinary Microbiology ( IF 3.3 ) Pub Date : 2020-09-29 , DOI: 10.1016/j.vetmic.2020.108863
Yongxiang Zhao , Zhongbao Song , Juan Bai , Xuewei Liu , Hans Nauwynck , Ping Jiang

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.



中文翻译:

猪繁殖与呼吸综合征病毒Nsp4裂解ZAP拮抗其抗病毒活性

猪繁殖与呼吸综合症病毒(PRRSV)是影响全球养猪业的最经济重要的病原体之一。已认识到PRRSV可通过多种机制调节宿主的免疫反应。在我们以前的研究中,我们发现宿主锌指抗病毒蛋白ZAP的过表达可以抑制PRRSV复制,但是在自然条件下PRRSV如何摆脱ZAP的限制仍然未知。在这项研究中,我们发现PRRSV感染显着下调Marc-145细胞中内源性ZAP蛋白的表达。并筛选了PRRSV非结构蛋白4(Nsp4)(一种3C样丝氨酸蛋白酶)来降低ZAP。Nsp4可以切割ZAP,具体取决于其蛋白酶活性。NAP4在Marc-145细胞中拮抗ZAP的抗PRRSV活性。此外,我们确定了一个独特的氨基酸,Nsp4的丝氨酸180是有效降解ZAP所必需的,残基180处的突变可能会降低重组PRRSV降解ZAP的能力。这些发现揭示了PRRSV Nsp4拮抗ZAP的抗病毒活性的方式,并阐明了PRRSV进化出的新策略以逃避宿主防御。

更新日期:2020-10-07
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