期刊
SIGNAL TRANSDUCTION AND TARGETED THERAPY
卷 6, 期 1, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41392-021-00742-w
关键词
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资金
- National Natural Science Foundation of China [81972873, 81871699, 82072330]
- Pearl River Talent Plan in Guangdong Province of China [2019CX01N111]
- Science and Technology Innovation Project in Foshan and Guangzhou, Guangdong Province, China [2020001000151, 202103000008]
- Foundation of Jilin Province Science and Technology Department [172408GH010234983, 20200301001RQ]
- China Postdoctoral Science Foundation [2020M680044]
The N protein of SARS-CoV-2 has a dual regulatory effect on innate immune responses, inhibiting signaling at low doses and promoting inflammation at high doses. This mechanism could help understand the pathogenesis of SARS-CoV-2 and develop better strategies for controlling COVID-19.
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.
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