Abstract

The newly emerging coronavirus SARS-CoV-2 causes severe lung disease and substantial mortality. How the virus evades host defense for efficient replication is not fully understood. In this report, we found that the SARS-CoV-2 nucleocapsid protein (NP) impaired stress granule (SG) formation induced by viral RNA. SARS-CoV-2 NP associated with the protein kinase PKR after dsRNA stimulation. SARS-CoV-2 NP did not affect dsRNA-induced PKR oligomerization, but impaired dsRNA-induced PKR phosphorylation (a hallmark of its activation) as well as SG formation. SARS-CoV-2 NP also targeted the SG-nucleating protein G3BP1 and impaired G3BP1-mediated SG formation. Deficiency of PKR or G3BP1 impaired dsRNA-triggered SG formation and increased SARS-CoV-2 replication. The NP of SARS-CoV also targeted both PKR and G3BP1 to impair dsRNA-induced SG formation, whereas the NP of MERS-CoV targeted PKR, but not G3BP1 for the impairment. Our findings suggest that SARS-CoV-2 NP promotes viral replication by impairing formation of antiviral SGs, and reveal a conserved mechanism on evasion of host antiviral responses by highly pathogenic human betacoronaviruses.

Details

Title
SARS-CoV-2 nucleocapsid protein impairs stress granule formation to promote viral replication
Author
Zhou-Qin, Zheng 1 ; Su-Yun, Wang 2 ; Zhi-Sheng, Xu 2 ; Yu-Zhi, Fu 2 ; Yan-Yi, Wang 1 

 Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China (GRID:grid.439104.b) (ISNI:0000 0004 1798 1925); University of Chinese Academy of Sciences, Beijing, China (GRID:grid.410726.6) (ISNI:0000 0004 1797 8419) 
 Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China (GRID:grid.439104.b) (ISNI:0000 0004 1798 1925) 
Publication year
2021
Publication date
2021
Publisher
Springer Nature B.V.
e-ISSN
20565968
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2531842248
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.