ArticleProceedings of the National Academy of Sciences of the United States of America2017
Coronavirus nonstructural protein 15 mediates evasion of dsRNA sensors and limits apoptosis in macrophages.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 241 papers, 1 of them a synthesis that pooled it.
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Who cites it
241 citing papers in PubMed, 1 synthesis or guideline pooled it, 405 citations in OpenAlex.
- The Reassessed Potential of SARS-CoV-2 Attenuation for COVID-19 Vaccine Development-A Systematic Review.Viruses · 2022Pooled it
- Relationship between gene expression patterns from nasopharyngeal swabs and serum biomarkers in patients hospitalized with COVID-19, following treatment with the neutralizing monoclonal antibody bamlanivimab.Journal of translational medicine · 2022Trial
- Coronavirus Nsp15 endoribonuclease: linking viral RNA regulation to immune evasion and viral fitness.Journal of virology · 2026Review
- Stress granules formed during infections with RNA viruses have significant virus-specific differences in generation and composition.PLoS biology · 2026Article
- Integrated multi-PTM omics reveals key host pathways in human coronavirus 229E infection.Redox biology · 2026Article
- Integrative modelling of innate immune response dynamics during virus infection.PLoS computational biology · 2026Article
- PKR condensation at viral replication complexes initiates its activation.Cell reports · 2026Article
- Redundant and distinct mechanisms suppress innate immune activation during SARS-CoV-2 infection.PLoS biology · 2026Article
- SARS-CoV-2 Nsp15 facilitates immune evasion and viral replication by limiting multiple host innate immune pathways, including cGAS-STING.The Journal of general virology · 2026Article
- Dynamic metabolic modelling of ATP allocation during viral infection.Journal of the Royal Society, Interface · 2026Article
- A murine coronavirus infection platform identifies proviral and proinflammatory activities of SARS-CoV-2 accessory protein 7a.Journal of virology · 2026Article
- Human alphacoronavirus replication and innate immune induction in airway culture systems.mBio · 2026Article
- Metal ions govern coronavirus endoribonuclease activity.Nucleic acids research · 2026Article
- MERS-CoV accessory ORF proteins in innate immune evasion: an evidence-graded functional framework.Frontiers in immunology · 2026Review
- Universal and quantitative detection of double-stranded RNAs as a signature of pan-virus infections using a luciferase-based biosensor.Journal of biological engineering · 2025Article
- SARS-CoV-2 EndoU-ribonuclease regulates RNA recombination and impacts viral fitness.Nature communications · 2025Article
- Development of the coronavirus reverse genetic system: Core technology for pathogenesis mechanisms research and vaccine/drug development.Virulence · 2025Review
- Cleavage sequence specificity of Nsp15.RNA biology · 2025Article
- A structural roadmap for the formation of the coronavirus nsp3/nsp4 double membrane vesicle pore and its implications for polyprotein processing and replication/transcription.Journal of virology · 2025Article
- How Does Porcine Epidemic Diarrhea Virus Escape Host Innate Immunity?Pathogens (Basel, Switzerland) · 2025Review
181 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Coronaviruses are positive-sense RNA viruses that generate double-stranded RNA (dsRNA) intermediates during replication, yet evade detection by host innate immune sensors. Here we report that coronavirus nonstructural protein 15 (nsp15), an endoribonuclease, is required for evasion of dsRNA sensors. We evaluated two independent nsp15 mutant mouse coronaviruses, designated N15m1 and N15m3, and found that these viruses replicated poorly and induced rapid cell death in mouse bone marrow-derived macrophages. Infection of macrophages with N15m1, which expresses an unstable nsp15, or N15m3, which expresses a catalysis-deficient nsp15, activated MDA5, PKR, and the OAS/RNase L system, resulting in an early, robust induction of type I IFN, PKR-mediated apoptosis, and RNA degradation. Immunofluorescence imaging of nsp15 mutant virus-infected macrophages revealed significant dispersal of dsRNA early during infection, whereas in WT virus-infected cells, the majority of the dsRNA was associated with replication complexes. The loss of nsp15 activity also resulted in greatly attenuated disease in mice and stimulated a protective immune response. Taken together, our findings demonstrate that coronavirus nsp15 is critical for evasion of host dsRNA sensors in macrophages and reveal that modulating nsp15 stability and activity is a strategy for generating live-attenuated vaccines.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.