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鉴定参与猪繁殖与呼吸综合征病毒进入易感细胞过程的肌球蛋白重链9关键结构域。

Identification of MYH9 Key Domain Involved in the Entry of PRRSV Into Permissive Cells.

作者信息

Li Liangliang, Sun Weiyao, Hu Qifan, Wang Tongtong, Zhu Guang, Zhao Qin, Zhou En-Min

机构信息

College of Agronomy, Liaocheng University, Liaocheng, China.

Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A and F University, Xianyang, China.

出版信息

Front Microbiol. 2022 May 25;13:865343. doi: 10.3389/fmicb.2022.865343. eCollection 2022.

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is an important pathogen that causes huge losses economically to the pig industry worldwide. Previous research suggested that receptor dependence is necessary for PRRSV infection. MYH9 and CD163 are indispensable for PRRSV entry into a porcine alveolar macrophage. In the present study, human MYH9 (hMYH9) and mouse MYH9 (mMYH9), similar to swine MYH9, could also accelerate PRRSV infection in pCD163-mediated cell lines. Knockdown of MYH9 activity using the specific small interfering RNA or inhibitor (blebbistatin) concomitantly decreased PRRSV infection. C-terminal fragment of MYH9 (PRA) proteins from different mammalian species contains a conserved binding domain (aa1676-1791) for PRRSV binding, since the recombinant MYH9protein could inhibit the PRRSV infection significantly. Furthermore, the specific polyclonal antibody of MYH9 could block PRRSV infection in host cells. These data strongly supported that MYH9, a very important cofactor, participated in PRRSV entry into target cells, which may facilitate the development of a new therapeutic agent to control PRRSV infection.

摘要

猪繁殖与呼吸综合征病毒(PRRSV)是一种重要的病原体,给全球养猪业造成巨大经济损失。先前的研究表明,受体依赖性是PRRSV感染所必需的。MYH9和CD163对于PRRSV进入猪肺泡巨噬细胞不可或缺。在本研究中,与猪MYH9相似,人MYH9(hMYH9)和小鼠MYH9(mMYH9)也能加速PRRSV在pCD163介导的细胞系中的感染。使用特异性小干扰RNA或抑制剂(blebbistatin)抑制MYH9活性可同时降低PRRSV感染。来自不同哺乳动物物种的MYH9的C末端片段(PRA)蛋白含有一个与PRRSV结合的保守结合域(aa1676 - 1791),因为重组MYH9蛋白可显著抑制PRRSV感染。此外,MYH9的特异性多克隆抗体可阻断宿主细胞中的PRRSV感染。这些数据有力地支持了MYH9作为一个非常重要的辅助因子参与PRRSV进入靶细胞,这可能有助于开发控制PRRSV感染的新型治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7074/9174932/48458eb74176/fmicb-13-865343-g0001.jpg

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