ArticleScience (New York, N.Y.)2021
A prenylated dsRNA sensor protects against severe COVID-19.
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Article in Science (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 164 papers, 1 of them a synthesis that pooled it.
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164citing papers in PubMed, 1 pooled it
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Who cites it
164 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- METTL3 promotes human coronavirus replication through an interferon-independent mechanism.bioRxiv : the preprint server for biology · 2026Article
- Cold-adapted RNA polymerase fromProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Loss of cellular RNA homeostasis contributes to MDA5 activation during virus infection.Nature immunology · 2026Article
- Temporal Dynamics of Innate Immune Activation and Viral Interference During Sequential Co-Infection with Influenza A Virus and SARS-CoV-2: Molecular Mechanisms, Clinical Evidence, and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Identifying severe COVID-19 risk variants modulating enhancer reporter activity in lung cells.PLoS genetics · 2026Article
- Alternative splicing broadens antiviral diversity at the human OAS2 locus.The EMBO journal · 2026Article
- SARS-CoV-2 5'-UTR stem-loops activate the antiviral protein oligoadenylate synthetase 1 (OAS1).The Journal of biological chemistry · 2026Article
- An ancient retrotransposon provides species-specific tuning of IL-18 inflammatory signaling.bioRxiv : the preprint server for biology · 2026Article
- SARS-CoV-2 5'-UTR stem-loops activate the antiviral protein oligoadenylate synthetase 1 (OAS1).bioRxiv : the preprint server for biology · 2026Article
- RNA-binding proteins and ribonucleoproteins as determinants of immunity.Nature reviews. Immunology · 2026Review
- Orthrus: toward evolutionary and functional RNA foundation models.Nature methods · 2026Article
- The Enzymatic Mechanism of OAS: How Metal Ions and Quantum Effects Help Activate Innate Immunity.ACS omega · 2026Article
- Article
- Entry, replication and innate immunity evasion of BANAL-236, a SARS-CoV-2-related bat virus, in Rhinolophus and human cells.PLoS pathogens · 2026Article
- The FunctionalInternational journal of molecular sciences · 2026Article
- Overexpression ofJournal of clinical medicine · 2026Article
- Unbiased cleavage site prediction uncovers viral antagonism of host innate immunity by SARS-CoV-2 3C-like protease.JCI insight · 2026Article
- IFITM3 deficiency drives SARS-CoV-2 adaptation while preserving variant-specific traits.Nature communications · 2026Article
- The OAS-RNase L pathway: Insights from experiments of nature.Science immunology · 2026Review
104 more citing papers are in PubMed but not listed here.
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Authors and funding
49 authors.
Arthur WickenhagenMedical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.ORCID 0000-0001-5470-1505
Elena Sugrue *Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.ORCID 0000-0001-5014-9522
Spyros Lytras *Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.ORCID 0000-0003-4202-6682
Srikeerthana Kuchi *Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
Marko Noerenberg *Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.ORCID 0000-0002-4834-8888
Matthew L Turnbull *Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.ORCID 0000-0002-7234-5871
Colin LoneyMedical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.ORCID 0000-0002-0508-1781
Vanessa HerderMedical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.ORCID 0000-0003-4814-1382
Jay AllanMedical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
Innes JarmsonMedical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
Natalia Cameron-RuizMedical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.ORCID 0000-0001-6945-1932
Margus VarjakMedical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.ORCID 0000-0003-2608-5148
Rute M PintoMedical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.ORCID 0000-0003-3291-1397
Jeffrey Y LeeDepartment of Biochemistry, University of Oxford, Oxford, UK.ORCID 0000-0002-5146-0037
Louisa IselinMedical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
Natasha PalmaluxMedical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.ORCID 0000-0002-4246-6082
Douglas G StewartMedical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
Simon SwinglerMedical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.ORCID 0000-0001-7317-8318
Edward J D GreenwoodCambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK.ORCID 0000-0002-5224-0263
Thomas W M CrozierCambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK.ORCID 0000-0003-0951-4588
Quan GuMedical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.ORCID 0000-0002-1201-6734
Emma L DaviesMedical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.ORCID 0000-0002-8416-9203
Sara ClohiseyRoslin Institute, University of Edinburgh, Edinburgh, UK.ORCID 0000-0001-7489-9846
Bo WangRoslin Institute, University of Edinburgh, Edinburgh, UK.ORCID 0000-0002-1580-797X
Fabio Trindade Maranhão CostaLaboratory of Tropical Diseases, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Sao Paolo, Brazil.ORCID 0000-0001-9969-7300
Monique Freire SantanaDepartment of Education and Research, Oncology Control Centre of Amazonas State (FCECON), Manaus, Amazonas, Brazil.ORCID 0000-0001-7849-6112
Luiz Carlos de Lima FerreiraPostgraduate Program in Tropical Medicine, Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil.ORCID 0000-0002-9657-939X
Lee MurphyEdinburgh Clinical Research Facility, University of Edinburgh, Western General Hospital, Edinburgh, UK.ORCID 0000-0001-6467-7449
Angie FawkesEdinburgh Clinical Research Facility, University of Edinburgh, Western General Hospital, Edinburgh, UK.ORCID 0000-0002-0657-8319
Alison MeynertMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.ORCID 0000-0001-5839-1751
Graeme GrimesMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
ISARIC4C Investigators
Joao Luiz Da Silva FilhoWellcome Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
Matthias MartiWellcome Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.ORCID 0000-0003-1040-9566
Joseph HughesMedical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.ORCID 0000-0003-2556-2563
Richard J StantonDivision of Infection & Immunity, Cardiff University, Cardiff, UK.ORCID 0000-0002-6799-1182
Eddie C Y WangDivision of Infection & Immunity, Cardiff University, Cardiff, UK.ORCID 0000-0002-2243-4964
Antonia HoMedical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
Ilan DavisDepartment of Biochemistry, University of Oxford, Oxford, UK.ORCID 0000-0002-5385-3053
Ruth F JarrettMedical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.ORCID 0000-0003-0390-3478
Alfredo CastelloMedical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.ORCID 0000-0002-1499-4662
David L RobertsonMedical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.ORCID 0000-0001-6338-0221
Malcolm G SempleNIHR Health Protection Research Unit for Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.ORCID 0000-0001-9700-0418
Peter J M OpenshawNational Heart and Lung Institute, Imperial College London, London, UK.ORCID 0000-0002-7220-2555
Massimo PalmariniMedical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.ORCID 0000-0001-7007-4070
Paul J LehnerCambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK.ORCID 0000-0001-9383-1054
J Kenneth BaillieRoslin Institute, University of Edinburgh, Edinburgh, UK.ORCID 0000-0001-5258-793X
Suzannah J RihnMedical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.ORCID 0000-0001-9495-4056
Sam J WilsonMedical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.ORCID 0000-0002-6065-0895
Funding
Biotechnology and Biological Sciences Research Council BB/M011224/1Department of Health CO-CIN-01Department of Health IS-BRC-1215-20013Medical Research Council G0701652Medical Research Council MC_PC_19025Medical Research Council MC_PC_19026Medical Research Council MC_PC_19059Medical Research Council MC_PC_20060Medical Research Council MC_UU_12014/10Medical Research Council MC_UU_12014/12Medical Research Council MC_UU_12014/3Medical Research Council MC_UU_12014/9Medical Research Council MR/K024752/1Medical Research Council MR/P001602/1Medical Research Council MR/P022642/1Medical Research Council MR/R021562/1Medical Research Council MR/S00971X/1Medical Research Council MR/S020039/1Medical Research Council MR/V000489/1Medical Research Council MR/V011561/1Medical Research Council MR/V028448/1Wellcome Trust 201366Wellcome Trust 201366/Z/16/ZWellcome Trust 204870/Z/16/ZWellcome Trust 209412Wellcome Trust 210688Wellcome Trust 210688/Z/18/Z
Abstract
Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severity. To better understand the antiviral defenses relevant to COVID-19, we used interferon-stimulated gene (ISG) expression screening to reveal that 2′-5′-oligoadenylate synthetase 1 (OAS1), through ribonuclease L, potently inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We show that a common splice-acceptor single-nucleotide polymorphism (Rs10774671) governs whether patients express prenylated OAS1 isoforms that are membrane-associated and sense-specific regions of SARS-CoV-2 RNAs or if they only express cytosolic, nonprenylated OAS1 that does not efficiently detect SARS-CoV-2. In hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting that this antiviral defense is a major component of a protective antiviral response.
Indexed as
2',5'-Oligoadenylate Synthetase5' Untranslated RegionsA549 CellsAnimalsChiropteraCoronaviridaeCOVID-19EndoribonucleasesHumansInterferonsIsoenzymesPhosphoric Diester HydrolasesPolymorphism, Single NucleotideProtein PrenylationRetroelementsRNA, Double-Stranded2-5A-dependent ribonuclease2',5'-Oligoadenylate Synthetase5' Untranslated RegionsEndoribonucleasesInterferonsIsoenzymesOAS1 protein, humanOAS3 protein, humanPhosphoric Diester HydrolasesRetroelementsRNA, Double-StrandedRNA, Viral
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