Portal de Periódicos da CAPES

Artigo Acesso aberto Produção Nacional Revisado por pares

BIBTEX RIS

A prenylated dsRNA sensor protects against severe COVID-19

2021; American Association for the Advancement of Science; Volume: 374; Issue: 6567 Linguagem: Inglês

10.1126/science.abj3624

1095-9203

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, Young Seok Lee, Louisa Iselin, Natasha Palmalux, Douglas G. Stewart, Simon Swingler, Edward JD Greenwood, Thomas W.M. Crozier, Quan Gu, Emma L. Davies, Sara Clohisey, Bo Wang, Fábio Trindade Maranhão Costa, Monique Freire Santana, Luíz Carlos de Lima Ferreira, Lee Murphy, Angie Fawkes, Alison Meynert, Graeme R. Grimes, João Luiz Silva‐Filho, Matthias Marti, Joseph Hughes, Richard J. Stanton, Eddie C. Y. Wang, Antonia Ho, Ilan Davis, Ruth F. Jarrett, Alfredo Castelló, David L. Robertson, Malcolm G. Semple, Peter J. M. Openshaw, Massimo Palmarini, Paul J. Lehner, J. Kenneth Baillie, Suzannah J. Rihn, Sam J. Wilson,

RNA and protein synthesis mechanisms

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.