A prenylated dsRNA sensor protects against severe COVID-19

Wickenhagen, A. et al. (2021) A prenylated dsRNA sensor protects against severe COVID-19. Science, 374(6567), eabj3624. (doi: 10.1126/science.abj3624) (PMID:34581622)

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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 OAS1, through RNase L, potently inhibits SARS-CoV-2. We show that a common splice-acceptor SNP (Rs10774671) governs whether people express prenylated OAS1 isoforms that are membrane-associated and sense specific regions of SARS-CoV-2 RNAs, or only express cytosolic, nonprenylated OAS1 that does not efficiently detect SARS-CoV-2. Importantly, in hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting this antiviral defense is a major component of a protective antiviral response.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Robertson, Professor David and Wickenhagen, Mr Arthur and Jarrett, Professor Ruth and Palmarini, Professor Massimo and Palmalux, Natasha and Castello, Dr Alfredo and Iselin, Louisa and Hughes, Dr Joseph and Turnbull, Dr Matthew and Baillie, Dr Kenneth and Wilson, Professor Sam and Lytras, Spyros and Gu, Dr Quan and Stewart, Mr Douglas and Cameron Ruiz, Natalia and Allan, Mr Jay and Swingler, Dr Simon and Herder, Dr Vanessa and Davies, Emma and Pinto, Dr Rute and Rihn, Dr Suzannah and Loney, Mr Colin and Ho, Dr Antonia and Kuchi, Dr Srikeerthana and Varjak, Dr Margus and Noerenberg, Dr Marko and Marti, Professor Matthias and Sugrue, Dr Elena and Jarmson, Innes
Authors: Wickenhagen, A., Sugrue, E., Lytras, S., Kuchi, S., Noerenberg, M., Turnbull, M. L., Loney, C., Herder, V., Allan, J., Jarmson, I., Cameron-Ruiz, N., Varjak, M., Pinto, R. M., Lee, J. Y., Iselin, L., Palmalux, N., Stewart, D. G., Swingler, S., Greenwood, E. J.D., Crozier, T. W.M., Gu, Q., Davies, E. L., Clohisey, S., Wang, B., Costa, F., Santana, M. F., Ferreira, L. C. d. L., Murphy, L., Fawkes, A., Meynert, A., Grimes, G., Da Silva Filho, J. L., Marti, M., Hughes, J., Stanton, R. J., Wang, E. C.Y., Ho, A., Davis, I., Jarrett, R. F., Castello, A., Robertson, D. L., Semple, M. G., Openshaw, P. J.M., Palmarini, M., Lehner, P. J., Baillie, J. K., Rihn, S. J., and Wilson, S. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Science
Publisher:American Association for the Advancement of Science
ISSN:0036-8075
ISSN (Online):1095-9203
Published Online:28 September 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Science 374(6567): eabj3624
Publisher Policy:Reproduced under a Creative Commons License
Related URLs:
Data DOI:10.5525/gla.researchdata.1178

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
168748Identifying and characterising antiretroviral interferon stimulated genes (ISGs)Sam WilsonMedical Research Council (MRC)MR/K024752/1III - Centre for Virus Research
Innate Immunity and Host Species BarriersMassimo PalmariniMedical Research Council (MRC)MC_UU_12014/10III - Centre for Virus Research
301840Host and Viral Determinants of Interferon Resistance During HIV-1 TransmissionSam WilsonMedical Research Council (MRC)MR/P022642/1III - Centre for Virus Research
173514Inhibition of HIV-1 by Type II InterferonSuzannah RihnWellcome Trust (WELLCOTR)201366/Z/16/ZIII - Centre for Virus Research
Viral Genomics and BioinformaticsAndrew DavisonMedical Research Council (MRC)MC_UU_12014/12III-MRC-GU Centre for Virus Research
310665ISARIC - Coronavirus Clinical Characterisation ConsortiumAntonia HoMedical Research Council (MRC)MC_PC_19059 - 9815274III - Centre for Virus Research