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

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

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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 ubiquitin-specific 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 poly-ubiquitination,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.

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

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

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Department of Laboratory Medicine,The Third Affiliated Hospital of Soochow University,Changzhou,213003,China

Hubei Hospital of Integrated Chinese and Western Medicine,Wuhan,430015,China

International Institute of Infection and Immunity,Institutes of Biology and Medical Sciences,Soochow University,Suzhou,215123,China

Jiangsu Key Laboratory of Infection and Immunity,Soochow University,Suzhou,215123,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaChangzhou science and technology support planChangzhou science and technology support planYoung Talent Development Plan of Changzhou Health Commission

8157205282102473CE20225036CJ202101412020-233

2023

中国病毒学
中国科学院武汉病毒研究所,中国微生物学会

中国病毒学

CSTPCDCSCD北大核心
影响因子:0.393
ISSN:1674-0769
年,卷(期):2023.(1)
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