ArticlePLoS pathogens2023
SARS-CoV-2 nucleocapsid protein inhibits the PKR-mediated integrated stress response through RNA-binding domain N2b.
Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
- SARS-CoV-2 defective viral genomes from distinct genomic regions drive divergent interferon responses.PLoS pathogens · 2026Article
- Identification of the SARS-CoV-2 genome packaging signal in the nsp12-coding region.Nature communications · 2026Article
- Evolution of a truncated nucleocapsid protein enhances SARS-CoV-2 fitness by suppressing antiviral responses.PLoS biology · 2026Article
- Phosphorylation Changes SARS-CoV-2 Nucleocapsid Protein's Structural Dynamics and Its Interaction With RNA.Proteins · 2025Article
- SARS-CoV-2 Nsp15 endoribonuclease subverts host defenses to enhance viral fitness in lung cells.Journal of virology · 2025Article
- Pattern Recognition Receptors (PRRs) Expression and Activation in COVID-19 and Long COVID: From SARS-CoV-2 Escape Mechanisms to Emerging PRR-Targeted Immunotherapies.Microorganisms · 2025Review
- Article
- IFN alpha inducible protein 27 (IFI27) acts as a positive regulator of PACT-dependent PKR activation after RNA virus infections.PLoS pathogens · 2025Article
- Pseudorabies virus IE180 protein hijacks G3BPs into the nucleus to inhibit stress granule formation.Journal of virology · 2025Article
- Variant mutation G215C in SARS-CoV-2 nucleocapsid enhances viral infection via altered genomic encapsidation.PLoS biology · 2025Article
- The transcriptional and translational landscape of HCoV-OC43 infection.PLoS pathogens · 2025Article
- The role of intrinsically disordered regions of SARS-CoV-2 nucleocapsid and non-structural protein 1 proteins.Frontiers in chemistry · 2025Review
- Regulating Immune Responses Induced by PEGylated Messenger RNA-Lipid Nanoparticle Vaccine.Vaccines · 2024Review
- A narrow ratio of nucleic acid to SARS-CoV-2 N-protein enables phase separation.bioRxiv : the preprint server for biology · 2024Article
- SARS-CoV-2 variant-specific differences in inhibiting the effects of the PKR-activated integrated stress response.Virus research · 2024Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nucleocapsid protein N of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enwraps and condenses the viral genome for packaging but is also an antagonist of the innate antiviral defense. It suppresses the integrated stress response (ISR), purportedly by interacting with stress granule (SG) assembly factors G3BP1 and 2, and inhibits type I interferon responses. To elucidate its mode of action, we systematically deleted and over-expressed distinct regions and domains. We show that N via domain N2b blocks PKR-mediated ISR activation, as measured by suppression of ISR-induced translational arrest and SG formation. N2b mutations that prevent dsRNA binding abrogate these activities also when introduced in the intact N protein. Substitutions reported to block post-translation modifications of N or its interaction with G3BP1/2 did not have a detectable additive effect. In an encephalomyocarditis virus-based infection model, N2b - but not a derivative defective in RNA binding-prevented PKR activation, inhibited β-interferon expression and promoted virus replication. Apparently, SARS-CoV-2 N inhibits innate immunity by sequestering dsRNA to prevent activation of PKR and RIG-I-like receptors. Similar observations were made for the N protein of human coronavirus 229E, suggesting that this may be a general trait conserved among members of other orthocoronavirus (sub)genera.
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