2. Academic Validation
  3. TRIM21 promotes ubiquitination of SARS-CoV-2 nucleocapsid protein to regulate innate immunity

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

  • J Med Virol. 2023 Apr;95(4):e28719. doi: 10.1002/jmv.28719.
Shenglan Mao 1 2,  Xuefei Cai 2,  Siqiang Niu 3,  Jie Wei 4,  Ning Jiang 5,  Haijun Deng 2,  Wen Wang 1 2,  Jing Zhang 1 2,  Shimei Shen 1 2,  Yuanyan Ma 1 2,  Xiaoli Wu 1 2,  Qiling Peng 5,  Ailong Huang 2,  Deqiang Wang 1 2
Affiliations

Affiliations

  • 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.
PMID: 37185839 DOI: 10.1002/jmv.28719
Abstract

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 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.

Keywords

SARS-CoV-2; TRIM21; innate immunity; nucleocapsid; ubiquitination.

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