Ubiquitin-specific protease 24 promotes EV71 infection by restricting K63-linked polyubiquitination of TBK1

作     者：Lichao Zang Jin Gu Xinyu Yang Yukang Yuan Hui Guo Wei Zhou Jinhong Ma Yan Chen Yumin Wu Hui Zheng Weifeng Shi Lichao Zang;Jin Gu;Xinyu Yang;Yukang Yuan;Hui Guo;Wei Zhou;Jinhong Ma;Yan Chen;Yumin Wu;Hui Zheng;Weifeng Shi

作者机构：Department of Laboratory MedicineThe Third Affiliated Hospital of Soochow UniversityChangzhou213003China International Institute of Infection and ImmunityInstitutes of Biology and Medical SciencesSoochow UniversitySuzhou215123China Jiangsu Key Laboratory of Infection and ImmunitySoochow UniversitySuzhou215123China Hubei Hospital of Integrated Chinese and Western MedicineWuhan430015China 

出 版 物：《Virologica Sinica》 (中国病毒学（英文版）)

年 卷 期：2023年第38卷第1期

页      面：75-83页

核心收录：

学科分类：0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学] 

基　　金：support was provided by the National Natural Science Foundation of China(81572052 and 82102473) Changzhou science and technology support plan(CE20225036,CJ20210141) Young Talent Development Plan of Changzhou Health Commission(2020-233). 

主　　题：Ubiquitin-specific protease 24(USP24) Enterovirus 71(EV71) TANK-binding kinase 1(TBK1) Type I interferons(IFN-I) Innate immunity 

摘      要：TANK-binding kinase 1(TBK1)is an essential protein kinase for activation of interferon regulatory factor 3(IRF3)and induction of the type I interferons(IFN-I).Although the biochemical regulation of TBK1 activation has been studied,little is known about how enterovirus 71(EV71)employs the deubiquitinases(DUBs)to regulate TBK1 activation for viral immune evasion.Here,we found that EV71 infection upregulated the expression of ubiquitinspecific protease 24(USP24).Further studies revealed that USP24 physically interacted with TBK1,and can reduce K63-linked polyubiquitination of TBK1.Knockdown of USP24 upregulated TBK1 K63-linked polyubiquitination,promoted the phosphorylation and nuclear translocation of IRF3,and in turn improved IFN-I production during EV71 infection.As a consequence,USP24 knockdown dramatically inhibited EV71 infection.This study revealed USP24 as a novel regulator of TBK1 activation,which promotes the understanding of immune evasion mechanisms of EV71 and could provide a potential strategy for treatment of EV71 infection.