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

文献类型： 外文期刊

作者： Zhao, Yinghua 1 ; Sui, Liyan 1 ; Wu, Ping 2 ; Wang, Wenfang 3 ; Wang, Zedong 1 ; Yu, Yang 4 ; Hou, Zhijun 2 ; Tan, Guangy 1 ;

作者机构： 1.Jilin Univ, Hosp 1, Minist Educ,State Key Lab Human Anim Zoonot Infec, Key Lab Organ Regenerat & Transplantat,Ctr Pathog, Changchun, Peoples R China

2.Northeast Forestry Univ, Coll Wildlife & Protected Area, Harbin, Peoples R China

3.Jilin Univ, Coll Basic Med, Chinese Minist Educ, Dept Pathogenbiol,Key Lab Zoonosis, Changchun, Peoples R China

4.Jilin Univ, Hosp Stomatol, Changchun, Peoples R China

5.Foshan Univ, Sch Life Sci & Engn, Foshan, Peoples R China

6.Guangdong Acad Agr Sci, Inst Anim Hlth, Guangzhou, Peoples R China

期刊名称：SIGNAL TRANSDUCTION AND TARGETED THERAPY （ 影响因子：18.187； 五年影响因子：21.177 ）

ISSN： 2095-9907

年卷期： 2021 年 6 卷 1 期

页码：

收录情况： SCI

摘要： 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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