TY - JOUR
AU - Wickenhagen, Arthur
AU - Sugrue, Elena
AU - Lytras, Spyros
AU - Kuchi, Srikeerthana
AU - Noerenberg, Marko
AU - Turnbull, Matthew L.
AU - Loney, Colin
AU - Herder, Vanessa
AU - Allan, Jay
AU - Jarmson, Innes
AU - Cameron-Ruiz, Natalia
AU - Varjak, Margus
AU - Pinto, Rute Maria
AU - Lee, Jeffrey Y.
AU - Iselin, Louisa
AU - Palmalux, Natasha
AU - Stewart, Douglas G.
AU - Swingler, Simon
AU - Greenwood, Edward J.D.
AU - Crozier, Thomas W.M.
AU - Gu, Quan
AU - Davies, Emma L.
AU - Clohisey, Sara
AU - Wang, Bo
AU - Costa, Fabio Trindade Maranhao
AU - Santana, Monique Freire
AU - Ferreria, Luiz Carlos de Lima
AU - Murphy, Lee
AU - Fawkes, Angie
AU - Meynert, Alison
AU - Grimes, Graeme
AU - ISARIC4C Investigators
AU - Filho, Joao Luiz da Silva
AU - Marti, Matthias
AU - Hughes, Joseph
AU - Stanton, Richard J.
AU - Wang, Eddie C.Y.
AU - Ho, Antonia
AU - Davis, Ilan
AU - Jarrett, Ruth F.
AU - Castello, Alfredo
AU - Robertson, David L.
AU - Semple, Malcolm G.
AU - Openshaw, Peter J.M.
AU - Palmarini, Massimo
AU - Lehner, Paul J.
AU - Baillie, J. Kenneth
AU - Rihn, Suzannah J.
AU - Wilson, Sam J.
PY - 2021
DA - September
TI - A prenylated dsRNA sensor protects against severe COVID-19
JO - Science
DO - https://doi.org/10.1126/science.abj3624
AB - 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.
PB - American Association for the Advancement of Science
UR - https://www.research.ed.ac.uk/en/publications/06b6455e-f6f8-45e2-af40-5ad3192d534c
KW - Coronavirus (COVID-19)
ER