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

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

doi:10.1016/j.virs.2022.11.001

February 2023

Citation: Lichao Zang, Jin Gu, Xinyu Yang, Yukang Yuan, Hui Guo, Wei Zhou, Jinhong Ma, Yan Chen, Yumin Wu, Hui Zheng, Weifeng Shi. Ubiquitin-specific protease 24 promotes EV71 infection by restricting K63-linked polyubiquitination of TBK1 .VIROLOGICA SINICA, 2023, 38(1) : 75-83. http://dx.doi.org/10.1016/j.virs.2022.11.001

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

Lichao Zang ^a ,
Jin Gu ^d ,
Xinyu Yang ^a ,
Yukang Yuan ^b,c ,
Hui Guo ^a ,
Wei Zhou ^a ,
Jinhong Ma ^a ,
Yan Chen ^a ,
Yumin Wu ^a ,
Hui Zheng ^{b,c
,,} ,
Weifeng Shi ^{a
,,}

a. Department of Laboratory Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China;
b. International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, 215123, China;
c. Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, 215123, China;
d. Hubei Hospital of Integrated Chinese and Western Medicine, Wuhan, 430015, China

Corresponding author: Hui Zheng, huizheng@suda.edu.cn
Weifeng Shi, swf67113@163.com
Received Date: 07 May 2022
Accepted Date: 31 October 2022
Available online: 02 November 2022

Abstract

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

Electronic Supplementary Material

10.1016j.virs.2022.11.001-ESM.docx
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