A dual-role of SARS-CoV-2 nucleocapsid protein in regulating innate immune response.
Signal Transduct Target Ther
; 6(1): 331, 2021 09 01.
Article
in English
| MEDLINE | ID: covidwho-1392811
ABSTRACT
The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of ongoing global pandemic of COVID-19, may trigger immunosuppression in the early stage and overactive immune response in the late stage of infection; However, the underlying mechanisms are not well understood. Here we demonstrated that the SARS-CoV-2 nucleocapsid (N) protein dually regulated innate immune responses, i.e., the low-dose N protein suppressed type I interferon (IFN-I) signaling and inflammatory cytokines, whereas high-dose N protein promoted IFN-I signaling and inflammatory cytokines. Mechanistically, the SARS-CoV-2 N protein dually regulated the phosphorylation and nuclear translocation of IRF3, STAT1, and STAT2. Additionally, low-dose N protein combined with TRIM25 could suppress the ubiquitination and activation of retinoic acid-inducible gene I (RIG-I). Our findings revealed a regulatory mechanism of innate immune responses by the SARS-CoV-2 N protein, which would contribute to understanding the pathogenesis of SARS-CoV-2 and other SARS-like coronaviruses, and development of more effective strategies for controlling COVID-19.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Signal Transduction
/
Coronavirus Nucleocapsid Proteins
/
SARS-CoV-2
/
COVID-19
/
Immunity, Innate
Limits:
Humans
Language:
English
Journal:
Signal Transduct Target Ther
Year:
2021
Document Type:
Article
Affiliation country:
S41392-021-00742-w
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