Affiliation:
1. Department of Laboratory Medicine Chongqing Medical University Chongqing China
2. The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education Chongqing Medical University Chongqing China
3. Department of Clinical Laboratory Medicine The First Affiliated Hospital of Chongqing Medical University Chongqing China
4. Department of Clinical Laboratory Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University) Zhuhai Guangdong China
5. School of Basic Medical Science Chongqing Medical University Chongqing China
Abstract
AbstractThe 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 Lys375. 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.
Funder
National Natural Science Foundation of China
Subject
Infectious Diseases,Virology
Cited by
6 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献