A prenylated dsRNA sensor protects against severe COVID-19.
Arthur Wickenhagen,Elena Sugrue,Spyros Lytras,Srikeerthana Kuchi,Marko Noerenberg,Matthew L. Turnbull,Colin Loney,Vanessa Herder,Jay Allan,Innes Jarmson,Natalia Cameron-Ruiz,Margus Varjak,Rute Maria Pinto,Jeffrey Y. Lee,Louisa Iselin,Louisa Iselin,Natasha Palmalux,Douglas G. Stewart,Simon Swingler,Edward J. D. Greenwood,Thomas W M Crozier,Quan Gu,Emma L. Davies,Sara Clohisey,Bo Wang,Fabio T. M. Costa,Monique Freire Santana,Luiz Carlos de Lima Ferreira,Lee Murphy,Angie Fawkes,Alison M. Meynert,Graeme R. Grimes,Isaric C Investigators,Joao Luiz Da Silva Filho,Matthias Marti,Joseph Hughes,Richard J. Stanton,Edward Chung Yern Wang,Antonia Ho,Ilan Davis,Ruth F. Jarrett,Alfredo Castello,David Robertson,Malcolm G Semple,Malcolm G Semple,Peter J. M. Openshaw,Peter J. M. Openshaw,Massimo Palmarini,Paul J. Lehner,J Kenneth Baillie,J Kenneth Baillie,Suzannah J. Rihn,Sam J. Wilson +52 more
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In this article, the authors used interferon-stimulated gene (ISG) expression screening to reveal that OAS1, through RNase L, potently inhibits SARS-CoV-2.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.read more
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Clash of the titans: interferons and SARS-CoV-2.
TL;DR: In this paper, the authors highlight important discoveries and discuss outstanding questions that will enable us to better understand the nuances of this evolutionary battle between interferons and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Posted ContentDOI
Human coronaviruses disassemble processing bodies
Carolyn-Ann Robinson,Mariel Kleer,Rory P. Mulloy,Rory P. Mulloy,Elizabeth L. Castle,Bre Q. Boudreau,Jennifer A. Corcoran,Jennifer A. Corcoran +7 more
TL;DR: Exposure to SARS-CoV-2 and the common cold hu CoVs, OC43 and 229E, induced PB loss is shown to contribute to enhanced proinflammatory cytokine production observed during severe Sars-Cov-2 infection.
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