The Nucleocapsid Proteins of SARS-CoV-2 and Its Close Relative Bat Coronavirus RaTG13 Are Capable of Inhibiting PKR- and RNase L-Mediated Antiviral Pathways.
G3BP1
PKR
RNase L
RaTG13
SARS-CoV-2 nucleocapsid
double-stranded RNA virus
vaccinia virus E3
Journal
Microbiology spectrum
ISSN: 2165-0497
Titre abrégé: Microbiol Spectr
Pays: United States
ID NLM: 101634614
Informations de publication
Date de publication:
15 06 2023
15 06 2023
Historique:
medline:
19
6
2023
pubmed:
8
5
2023
entrez:
8
5
2023
Statut:
ppublish
Résumé
Coronaviruses (CoVs), including severe acute respiratory syndrome CoV (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and SARS-CoV-2, produce double-stranded RNA (dsRNA) that activates antiviral pathways such as PKR and OAS/RNase L. To successfully replicate in hosts, viruses must evade such antiviral pathways. Currently, the mechanism of how SARS-CoV-2 antagonizes dsRNA-activated antiviral pathways is unknown. In this study, we demonstrate that the SARS-CoV-2 nucleocapsid (N) protein, the most abundant viral structural protein, is capable of binding to dsRNA and phosphorylated PKR, inhibiting both the PKR and OAS/RNase L pathways. The N protein of the bat coronavirus (bat-CoV) RaTG13, the closest relative of SARS-CoV-2, has a similar ability to inhibit the human PKR and RNase L antiviral pathways. Via mutagenic analysis, we found that the C-terminal domain (CTD) of the N protein is sufficient for binding dsRNA and inhibiting RNase L activity. Interestingly, while the CTD is also sufficient for binding phosphorylated PKR, the inhibition of PKR antiviral activity requires not only the CTD but also the central linker region (LKR). Thus, our findings demonstrate that the SARS-CoV-2 N protein is capable of antagonizing the two critical antiviral pathways activated by viral dsRNA and that its inhibition of PKR activities requires more than dsRNA binding mediated by the CTD.
Identifiants
pubmed: 37154717
doi: 10.1128/spectrum.00994-23
pmc: PMC10269842
doi:
Substances chimiques
2-5A-dependent ribonuclease
EC 3.1.26.-
Antiviral Agents
0
Nucleocapsid Proteins
0
Viral Proteins
0
RNA, Double-Stranded
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0099423Subventions
Organisme : NIAID NIH HHS
ID : R01 AI151638
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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