ArticlePLoS pathogens2017
Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04672291 (A Phase I-Ib, Double-blinded, Randomized Repeated Dose Single Center, Safety and Immunogenicity Study of Nasal Poly-ICLC), which is not on this map. Cited by 165 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I-Ib, Double-blinded, Randomized Repeated Dose Single Center, Safety and Immunogenicity Study of Nasal Poly-ICLC (Hiltonol®) in Healthy COVID-19 Vaccinated Adults
Who cites it
165 citing papers in PubMed, 1 synthesis or guideline pooled it, 245 citations in OpenAlex.
- The Reassessed Potential of SARS-CoV-2 Attenuation for COVID-19 Vaccine Development-A Systematic Review.Viruses · 2022Pooled it
- 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
- PKR condensation at viral replication complexes initiates its activation.Cell reports · 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
- A murine coronavirus infection platform identifies proviral and proinflammatory activities of SARS-CoV-2 accessory protein 7a.Journal of virology · 2026Article
- Metal ions govern coronavirus endoribonuclease activity.Nucleic acids research · 2026Article
- Human alphacoronavirus replication and innate immune induction in airway culture systems.mBio · 2026Article
- SARS-CoV-2 EndoU-ribonuclease regulates RNA recombination and impacts viral fitness.Nature communications · 2025Article
- Characteristics of an emerging canine respiratory coronavirus in China.The veterinary quarterly · 2025Article
- Cleavage sequence specificity of Nsp15.RNA biology · 2025Article
- Tonic type I interferon signaling optimizes the antiviral function of plasmacytoid dendritic cells.Nature immunology · 2025Article
- How Does Porcine Epidemic Diarrhea Virus Escape Host Innate Immunity?Pathogens (Basel, Switzerland) · 2025Review
- SARS-CoV-2 Nsp15 endoribonuclease subverts host defenses to enhance viral fitness in lung cells.Journal of virology · 2025Article
- Engineering a recombination-resistant live attenuated vaccine candidate with suppressed interferon antagonists for PEDV.Journal of virology · 2025Article
- SARS-CoV-2 nsp15 enhances viral virulence by subverting host antiviral defenses.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Identification of acrylamide-based covalent inhibitors of SARS-CoV-2 (SCoV-2) Nsp15 using high-throughput screening and machine learning.RSC advances · 2025Article
- Human coronaviruses: activation and antagonism of innate immune responses.Microbiology and molecular biology reviews : MMBR · 2025Review
- Coronavirus endoribonuclease antagonizes ZBP1-mediated necroptosis and delays multiple cell death pathways.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Coronavirus endoribonuclease nsp15 suppresses host protein synthesis and evades PKR-eIF2α-mediated translation shutoff to ensure viral protein synthesis.PLoS pathogens · 2025Article
105 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors at 13 institutions in 5 countries.
Funding
Abstract
Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I). This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU) activity is key to prevent early induction of double-stranded RNA (dsRNA) host cell responses. Replication of EndoU-deficient coronaviruses is greatly attenuated in vivo and severely restricted in primary cells even during the early phase of the infection. In macrophages we found immediate induction of IFN-I expression and RNase L-mediated breakdown of ribosomal RNA. Accordingly, EndoU-deficient viruses can retain replication only in cells that are deficient in IFN-I expression or sensing, and in cells lacking both RNase L and PKR. Collectively our results demonstrate that the coronavirus EndoU efficiently prevents simultaneous activation of host cell dsRNA sensors, such as Mda5, OAS and PKR. The localization of the EndoU activity at the site of viral RNA synthesis-within the replicase complex-suggests that coronaviruses have evolved a viral RNA decay pathway to evade early innate and intrinsic antiviral host cell responses.
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Registered trials
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.