SHFL inhibits enterovirus A71 infection by triggering degradation of viral 3D<SUP>pol</SUP> protein via the ubiquitin-proteasome pathway

作者全名："Tan, Chahui; Qin, Xingliang; Tan, Yongyao; Dong, Xinhuai; Chen, Delin; Liang, Linyue; Li, Jinling; Niu, Ruoxi; Cao, Kaiyuan; He, Zhenjian; Wei, Guohong; Huang, Mingxing; Zhu, Xun"

作者地址："[Tan, Chahui; Qin, Xingliang; Tan, Yongyao; Chen, Delin; Liang, Linyue; Li, Jinling; Cao, Kaiyuan; He, Zhenjian; Zhu, Xun] Sun Yat sen Univ, Key Lab Trop Dis Control, Minist Educ, Guangzhou, Peoples R China; [Tan, Chahui; Qin, Xingliang; Tan, Yongyao; Chen, Delin; Liang, Linyue; Li, Jinling; Cao, Kaiyuan; Zhu, Xun] Sun Yat sen Univ, Res Ctr Clin Lab Stand, Zhongshan Sch Med, Dept Immunol & Microbiol, Guangzhou, Peoples R China; [Tan, Chahui] Changsha Med Univ, Dept Lab Med, Changsha, Peoples R China; [Dong, Xinhuai] Southern Med Univ, Shunde Hosp, Peoples Hosp Shunde 1, Med Res Ctr, Foshan, Peoples R China; [Niu, Ruoxi] Chongqing Med Univ, Univ Town Hosp, Dept Clin Lab Med, Chongqing, Peoples R China; [He, Zhenjian] Sun Yat Sen Univ, Sch Publ Hlth, Guangzhou, Peoples R China; [Wei, Guohong] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Endocrinol, Guangzhou, Peoples R China; [Huang, Mingxing; Zhu, Xun] Third Peoples Hosp Zhuhai, Cent Lab, Zhuhai, Peoples R China; [Zhu, Xun] Guangdong Prov Key Lab Orthoped & Traumatol, Guangzhou, Peoples R China; [He, Zhenjian] Sun Yat sen Univ, Sch Publ Hlth, Guangzhou 510080, Peoples R China; [Wei, Guohong] Sun Yat sen Univ, Affiliated Hosp 1, Guangzhou 510080, Peoples R China; [Huang, Mingxing] Third Peoples Hosp Zhuhai, Zhuhai 519060, Peoples R China; [Zhu, Xun] Sun Yat sen Univ, Zhongshan Sch Med, 74 Zhongshan Rd 2, Guangzhou 510080, Guangdong, Peoples R China"

通信作者："He, ZJ (通讯作者)，Sun Yat sen Univ, Sch Publ Hlth, Guangzhou 510080, Peoples R China.; Wei, GH (通讯作者)，Sun Yat sen Univ, Affiliated Hosp 1, Guangzhou 510080, Peoples R China.; Huang, MX (通讯作者)，Third Peoples Hosp Zhuhai, Zhuhai 519060, Peoples R China.; Zhu, X (通讯作者)，Sun Yat sen Univ, Zhongshan Sch Med, 74 Zhongshan Rd 2, Guangzhou 510080, Guangdong, Peoples R China."

来源：JOURNAL OF MEDICAL VIROLOGY

ESI学科分类：MICROBIOLOGY

WOS号：WOS:001059179200079

JCR分区：Q1

影响因子：6.8

年份：2023

卷号：95

期号：8

开始页：　

结束页：　

文献类型：Article

关键词：enterovirus A71; hand-foot-mouth disease; interferon; interferon-stimulated genes; SHFL

摘要："Enterovirus A71 (EV-A71) is a highly contagious virus that poses a major threat to global health, representing the primary etiological agent for hand-foot and mouth disease (HFMD) and neurological complications. It has been established that interferon signaling is critical to establishing a robust antiviral state in host cells, mainly mediated through the antiviral effects of numerous interferon-stimulated genes (ISGs). The host restriction factor SHFL is a novel ISG with broad antiviral activity against various viruses through diverse underlying molecular mechanisms. Although SHFL is widely acknowledged for its broad-spectrum antiviral activity, it remains elusive whether SHFL inhibits EV-A71. In this work, we validated that EV-A71 triggers the upregulation of SHFL both in cell lines and in a mouse model. Knockdown and overexpression of SHFL in EVA71-infected cells suggested that this factor could markedly suppress EV-A71 replication. Our findings further revealed an intriguing mechanism of SHFL that it could interact with the nonstructural proteins 3Dpol of EV-A71 and promoted the degradation of 3Dpol through the ubiquitin-proteasome pathway. Furthermore, the zinc-finger domain and the 36 amino acids (164-199) of SHFL were crucial to the interaction between SHFL and EV-A71 3Dpol. Overall, these findings broadened our understanding of the pivotal roles of SHFL in the interaction between the host and EV-A71."

基金机构："This work was supported by grants from the National Natural Science Foundation of China (82071352, 81971146, 82171675), Guangdong Basic and Applied Basic Research Foundation (2022A1515011156, 2021A1515010458), Guangdong Marine Economy Development Special P [81971146, 82171675, 2022A1515011156]; National Natural Science Foundation of China [2021A1515010458, [2022]35]; Guangdong Basic and Applied Basic Research Foundation; Guangdong Marine Economy Development Special Project; [82071352]"

基金资助正文："This work was supported by grants from the National Natural Science Foundation of China (82071352, 81971146, 82171675), Guangdong Basic and Applied Basic Research Foundation (2022A1515011156, 2021A1515010458), Guangdong Marine Economy Development Special Project (No. GDNRC [2022]35)."