TRIM21 promotes ubiquitination of SARS-CoV-2 nucleocapsid protein to regulate innate immunity

作者全名："Mao, Shenglan; Cai, Xuefei; Niu, Siqiang; Wei, Jie; Jiang, Ning; Deng, Haijun; Wang, Wen; Zhang, Jing; Shen, Shimei; Ma, Yuanyan; Wu, Xiaoli; Peng, Qiling; Huang, Ailong; Wang, Deqiang"

作者地址："[Mao, Shenglan; Wang, Wen; Zhang, Jing; Shen, Shimei; Ma, Yuanyan; Wu, Xiaoli; Wang, Deqiang] Chongqing Med Univ, Dept Lab Med, Chongqing 400016, Peoples R China; [Mao, Shenglan; Cai, Xuefei; Deng, Haijun; Wang, Wen; Zhang, Jing; Shen, Shimei; Ma, Yuanyan; Wu, Xiaoli; Huang, Ailong; Wang, Deqiang] Chongqing Med Univ, Chinese Minist Educ, Key Lab Mol Biol Infect Dis, Chongqing 400016, Peoples R China; [Niu, Siqiang] Chongqing Med Univ, Dept Clin Lab Med, Affiliated Hosp 1, Chongqing, Peoples R China; [Wei, Jie] Jinan Univ, Zhuhai Peoples Hosp, Dept Clin Lab, Zhuhai Hosp, Zhuhai, Guangdong, Peoples R China; [Jiang, Ning; Peng, Qiling] Chongqing Med Univ, Sch Basic Med Sci, Chongqing 400016, Peoples R China"

通信作者："Wang, DQ (通讯作者)，Chongqing Med Univ, Dept Lab Med, Chongqing 400016, Peoples R China.; Huang, AL; Wang, DQ (通讯作者)，Chongqing Med Univ, Chinese Minist Educ, Key Lab Mol Biol Infect Dis, Chongqing 400016, Peoples R China.; Peng, QL (通讯作者)，Chongqing Med Univ, Sch Basic Med Sci, Chongqing 400016, Peoples R China."

来源：JOURNAL OF MEDICAL VIROLOGY

ESI学科分类：MICROBIOLOGY

WOS号：WOS:000989594000015

JCR分区：Q1

影响因子：6.8

年份：2023

卷号：95

期号：4

开始页：　

结束页：　

文献类型：Article

关键词：innate immunity; nucleocapsid; SARS-CoV-2; TRIM21; ubiquitination

摘要："The innate immune response is the first line of host defense against viral infections, but its role in immunity against SARS-CoV-2 remains unclear. By using immunoprecipitation coupled with mass spectroscopy, we observed that the E3 ubiquitin ligase TRIM21 interacted with the SARS-CoV-2 nucleocapsid (N) protein and ubiquitinated it at Lys(375). Upon determining the topology of the TRIM21-mediated polyubiquitination chain on N protein, we then found that polyubiquitination led to tagging of the N protein for degradation by the host cell proteasome. Furthermore, TRIM21 also ubiquitinated the N proteins of SARS-CoV-2 variants of concern, including Alpha, Beta, Gamma, Delta, and Omicron together with SARS-CoV and MERS-CoV variants. Herein, we propose that ubiquitylation and degradation of the SARS-CoV-2 N protein inhibited SARS-CoV-2 viral particle assembly, by which it probably involved in preventing cytokine storm. Eventually, our study has fully revealed the association between the host innate immune system and SARS-CoV-2 N protein, which may aid in developing novel SARS-CoV-2 treatment strategies."

基金机构："National Science and Technology Major Project [2017ZX10202203, 2018ZX10732202]; National Natural Science Foundation of China [81661148057, 81972023]; Chongqing Talents Programs; Municipal Natural Science Foundation of Chongqing [cstc2018jscx-msyb0004, cstc2020jscx-fyzxX0020]; CQMU Program for Youth Innovation in Future Medicine [W0031]; Guangdong Basic and Applied Basic Research Foundation"

基金资助正文："National Science and Technology Major Project, Grant/Award Numbers: 2017ZX10202203, 2018ZX10732202; National Natural Science Foundation of China, Grant/Award Numbers: 81661148057, 81972023; Chongqing Talents Programs; Municipal Natural Science Foundation of Chongqing, Grant/Award Numbers: cstc2018jscx-msyb0004, cstc2020jscx-fyzxX0020; CQMU Program for Youth Innovation in Future Medicine, Grant/Award Number: W0031; Guangdong Basic and Applied Basic Research Foundation"