Heat shock protein A1 inhibits the replication of foot-and-mouth disease virus by degrading viral RNA polymerase 3D through chaperone-mediated autophagy.

IF 4 2区 医学 Q2 VIROLOGY
Mei Ren, Haiqian Zhou, Jin-En Wu, Jia-Ning Wang, Xuefei Wang, Sahibzada Waheed Abdullah, Huichen Guo, Shiqi Sun
{"title":"Heat shock protein A1 inhibits the replication of foot-and-mouth disease virus by degrading viral RNA polymerase 3D through chaperone-mediated autophagy.","authors":"Mei Ren, Haiqian Zhou, Jin-En Wu, Jia-Ning Wang, Xuefei Wang, Sahibzada Waheed Abdullah, Huichen Guo, Shiqi Sun","doi":"10.1128/jvi.00168-25","DOIUrl":null,"url":null,"abstract":"<p><p>Foot-and-mouth disease virus (FMDV), a member of the <i>Picornaviridae</i> family, is a single-stranded, positive-sense RNA virus. Heat shock protein A1 (HSPA1) has been shown to influence the entry, translation, assembly, and release of enterovirus A71 (EV-A71), another <i>Picornaviridae</i> family member. In this study, we demonstrate that HSPA1 plays a different role in the replication of FMDV. By investigating various stages of virus replication, we found that HSPA1 specifically inhibits the RNA replication stage in which HSPA1 inhibits viral RNA replication by degrading the viral RNA-dependent RNA polymerase (RdRp), 3D protein. In the presence of specific inhibitors, we find out that this degradation occurs through the autophagy pathway. Activation and blockage of chaperone-mediated autophagy (CMA) demonstrate that HSPA1 degrades 3D through the CMA pathway. Mutation analysis reveals that <sub>421</sub>QEKLI<sub>425</sub> is the key motif in 3D responsible for HSPA1-mediated CMA degradation. In summary, this study shows that HSPA1 can degrade the viral 3D protein through the CMA pathway, thereby inhibiting the RNA replication of FMDV and interfering with virus infection. This study, for the first time, demonstrates that HSPA1 employs its chaperone function to mediate the degradation of the FMDV RdRp, revealing the crucial role of HSPA1 in the FMDV infection process and suggesting that HSPA1 could be a potential target for the prevention and treatment of FMDV infection.</p><p><strong>Importance: </strong>Viral RNA replication is the key stage in understanding the pathogenic mechanisms of foot-and-mouth disease virus (FMDV). During this process, the viral non-structural protein 3D serves as an RNA-dependent RNA polymerase (RdRp) to synthesize progeny RNA using the viral genomic RNA as a template. However, the regulatory effect of host cells on FMDV 3D proteins has not yet been studied. In this study, we find that heat shock protein A1 (HSPA1) degrades the viral 3D protein through the chaperone-mediated autophagy (CMA) pathway, thereby inhibiting the RNA replication of FMDV and interfering with virus infection. This study, for the first time, demonstrates that HSPA1 employs its chaperone function to mediate the degradation of the FMDV RdRp.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0016825"},"PeriodicalIF":4.0000,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Virology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1128/jvi.00168-25","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"VIROLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Foot-and-mouth disease virus (FMDV), a member of the Picornaviridae family, is a single-stranded, positive-sense RNA virus. Heat shock protein A1 (HSPA1) has been shown to influence the entry, translation, assembly, and release of enterovirus A71 (EV-A71), another Picornaviridae family member. In this study, we demonstrate that HSPA1 plays a different role in the replication of FMDV. By investigating various stages of virus replication, we found that HSPA1 specifically inhibits the RNA replication stage in which HSPA1 inhibits viral RNA replication by degrading the viral RNA-dependent RNA polymerase (RdRp), 3D protein. In the presence of specific inhibitors, we find out that this degradation occurs through the autophagy pathway. Activation and blockage of chaperone-mediated autophagy (CMA) demonstrate that HSPA1 degrades 3D through the CMA pathway. Mutation analysis reveals that 421QEKLI425 is the key motif in 3D responsible for HSPA1-mediated CMA degradation. In summary, this study shows that HSPA1 can degrade the viral 3D protein through the CMA pathway, thereby inhibiting the RNA replication of FMDV and interfering with virus infection. This study, for the first time, demonstrates that HSPA1 employs its chaperone function to mediate the degradation of the FMDV RdRp, revealing the crucial role of HSPA1 in the FMDV infection process and suggesting that HSPA1 could be a potential target for the prevention and treatment of FMDV infection.

Importance: Viral RNA replication is the key stage in understanding the pathogenic mechanisms of foot-and-mouth disease virus (FMDV). During this process, the viral non-structural protein 3D serves as an RNA-dependent RNA polymerase (RdRp) to synthesize progeny RNA using the viral genomic RNA as a template. However, the regulatory effect of host cells on FMDV 3D proteins has not yet been studied. In this study, we find that heat shock protein A1 (HSPA1) degrades the viral 3D protein through the chaperone-mediated autophagy (CMA) pathway, thereby inhibiting the RNA replication of FMDV and interfering with virus infection. This study, for the first time, demonstrates that HSPA1 employs its chaperone function to mediate the degradation of the FMDV RdRp.

热休克蛋白A1通过伴侣介导的自噬作用降解病毒RNA聚合酶3D,从而抑制口蹄疫病毒的复制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Journal of Virology
Journal of Virology 医学-病毒学
CiteScore
10.10
自引率
7.40%
发文量
906
审稿时长
1 months
期刊介绍: Journal of Virology (JVI) explores the nature of the viruses of animals, archaea, bacteria, fungi, plants, and protozoa. We welcome papers on virion structure and assembly, viral genome replication and regulation of gene expression, genetic diversity and evolution, virus-cell interactions, cellular responses to infection, transformation and oncogenesis, gene delivery, viral pathogenesis and immunity, and vaccines and antiviral agents.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信