RING finger protein 5 is a key anti-FMDV host factor through inhibition of virion assembly.

IF 5.5 1区医学 Q1 MICROBIOLOGY

PLoS Pathogens Pub Date : 2025-01-17 eCollection Date: 2025-01-01 DOI:10.1371/journal.ppat.1012848

Wei Zhang, Weiwei Li, Yang Yang, Weijun Cao, Wenhua Shao, Mengyao Huang, Jiali Wang, Zhitong Chen, Jiantao Cai, Hongyi Liu, Xiaoyi Zhao, Xingyan Dong, Tingting Zhou, Hong Tian, Zixiang Zhu, Fan Yang, Haixue Zheng

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引用次数: 0

Abstract

Foot-and-mouth disease virus (FMDV) are small, icosahedral viruses that cause serious clinical symptoms in livestock. The FMDV VP1 protein is a key structural component, facilitating virus entry. Here, we find that the E3 ligase RNF5 interacts with VP1 and targets it for degradation through ubiquitination at the lys200 of VP1, ultimately inhibiting virus replication. Mutations at this lysine site have been found to increase the replication of FMDV in mice. Importantly, the RNF5 pharmacological activator Analog-1 alleviates disease development in a mouse infection model. Furthermore, RNF5 recognizes the VP1 protein from several picornaviruses, suggesting that targeting RNF5 may be a broad-spectrum antiviral strategy. These findings shed light on the role of the ubiquitin-proteasome system in controlling virus replication, offering potential new strategies for treating viral infections.

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无名指蛋白5通过抑制病毒粒子组装而成为抗fmdv的关键宿主因子。

口蹄疫病毒（FMDV）是一种小的二十面体病毒，可在牲畜中引起严重的临床症状。FMDV VP1蛋白是促进病毒进入的关键结构成分。在这里，我们发现E3连接酶RNF5与VP1相互作用，并通过在VP1的lys200处泛素化使其降解，最终抑制病毒复制。该赖氨酸位点的突变已被发现可增加小鼠FMDV的复制。重要的是，RNF5药理激活物Analog-1可缓解小鼠感染模型中的疾病发展。此外，RNF5可以识别几种小核糖核酸病毒的VP1蛋白，这表明靶向RNF5可能是一种广谱抗病毒策略。这些发现揭示了泛素-蛋白酶体系统在控制病毒复制中的作用，为治疗病毒感染提供了潜在的新策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

PLoS Pathogens MICROBIOLOGY-PARASITOLOGY

自引率

3.00%

发文量

598

期刊介绍： Bacteria, fungi, parasites, prions and viruses cause a plethora of diseases that have important medical, agricultural, and economic consequences. Moreover, the study of microbes continues to provide novel insights into such fundamental processes as the molecular basis of cellular and organismal function.