Signal Transduction and Targeted Therapy (Sep 2021)

A dual-role of SARS-CoV-2 nucleocapsid protein in regulating innate immune response

  • Yinghua Zhao,
  • Liyan Sui,
  • Ping Wu,
  • Wenfang Wang,
  • Zedong Wang,
  • Yang Yu,
  • Zhijun Hou,
  • Guangyun Tan,
  • Quan Liu,
  • Guoqing Wang

DOI
https://doi.org/10.1038/s41392-021-00742-w
Journal volume & issue
Vol. 6, no. 1
pp. 1 – 14

Abstract

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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.