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A prenylated dsRNA sensor protects against severe COVID-19.
Wickenhagen, Arthur; Sugrue, Elena; Lytras, Spyros; Kuchi, Srikeerthana; Noerenberg, Marko; Turnbull, Matthew L; Loney, Colin; Herder, Vanessa; Allan, Jay; Jarmson, Innes; Cameron-Ruiz, Natalia; Varjak, Margus; Pinto, Rute M; Lee, Jeffrey Y; Iselin, Louisa; Palmalux, Natasha; Stewart, Douglas G; Swingler, Simon; Greenwood, Edward J D; Crozier, Thomas W M; Gu, Quan; Davies, Emma L; Clohisey, Sara; Wang, Bo; Trindade Maranhão Costa, Fabio; Freire Santana, Monique; de Lima Ferreira, Luiz Carlos; Murphy, Lee; Fawkes, Angie; Meynert, Alison; Grimes, Graeme; Da Silva Filho, Joao Luiz; Marti, Matthias; Hughes, Joseph; Stanton, Richard J; Wang, Eddie C Y; Ho, Antonia; Davis, Ilan; Jarrett, Ruth F; Castello, Alfredo; Robertson, David L; Semple, Malcolm G; Openshaw, Peter J M; Palmarini, Massimo; Lehner, Paul J; Baillie, J Kenneth; Rihn, Suzannah J; Wilson, Sam J.
  • Wickenhagen A; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Sugrue E; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Lytras S; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Kuchi S; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Noerenberg M; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Turnbull ML; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Loney C; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Herder V; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Allan J; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Jarmson I; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Cameron-Ruiz N; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Varjak M; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Pinto RM; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Lee JY; Department of Biochemistry, University of Oxford, Oxford, UK.
  • Iselin L; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Palmalux N; Department of Biochemistry, University of Oxford, Oxford, UK.
  • Stewart DG; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Swingler S; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Greenwood EJD; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Crozier TWM; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Gu Q; Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK.
  • Davies EL; Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK.
  • Clohisey S; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Wang B; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Trindade Maranhão Costa F; Roslin Institute, University of Edinburgh, Edinburgh, UK.
  • Freire Santana M; Roslin Institute, University of Edinburgh, Edinburgh, UK.
  • de Lima Ferreira LC; Laboratory of Tropical Diseases, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Sao Paolo, Brazil.
  • Murphy L; Department of Education and Research, Oncology Control Centre of Amazonas State (FCECON), Manaus, Amazonas, Brazil.
  • Fawkes A; Postgraduate Program in Tropical Medicine, Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil.
  • Meynert A; Edinburgh Clinical Research Facility, University of Edinburgh, Western General Hospital, Edinburgh, UK.
  • Grimes G; Edinburgh Clinical Research Facility, University of Edinburgh, Western General Hospital, Edinburgh, UK.
  • Da Silva Filho JL; Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
  • Hughes J; Wellcome Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
  • Stanton RJ; Wellcome Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
  • Wang ECY; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Ho A; Division of Infection & Immunity, Cardiff University, Cardiff, UK.
  • Davis I; Division of Infection & Immunity, Cardiff University, Cardiff, UK.
  • Jarrett RF; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Castello A; Department of Biochemistry, University of Oxford, Oxford, UK.
  • Robertson DL; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Semple MG; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Openshaw PJM; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
  • Palmarini M; NIHR Health Protection Research Unit for Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
  • Lehner PJ; Respiratory Medicine, Alder Hey Children's Hospital, Liverpool, UK.
  • Baillie JK; National Heart and Lung Institute, Imperial College London, London, UK.
  • Rihn SJ; Imperial College Healthcare, National Health Service Trust London, London, UK.
  • Wilson SJ; Medical Research Council-University of Glasgow Centre for Virus Research (CVR), Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
Science ; 374(6567): eabj3624, 2021 Oct 29.
Article in English | MEDLINE | ID: covidwho-1440797
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: 2',5'-Oligoadenylate Synthetase / RNA, Double-Stranded / RNA, Viral / SARS-CoV-2 / COVID-19 Type of study: Diagnostic study / Prognostic study Limits: Animals / Humans Language: English Journal: Science Year: 2021 Document Type: Article Affiliation country: Science.abj3624

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Full text: Available Collection: International databases Database: MEDLINE Main subject: 2',5'-Oligoadenylate Synthetase / RNA, Double-Stranded / RNA, Viral / SARS-CoV-2 / COVID-19 Type of study: Diagnostic study / Prognostic study Limits: Animals / Humans Language: English Journal: Science Year: 2021 Document Type: Article Affiliation country: Science.abj3624