- Published
- 28 September 2021
- Journal article
A prenylated dsRNA sensor protects against severe COVID-19
- Authors
-
Wang, Bo ;
- Source
- Science
Full text
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.
Rights
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Cite as
Wickenhagen, A., Sugrue, E., Lytras, S., Kuchi, S., Noerenberg, M., Turnbull, M., Loney, C., Herder, V., Allan, J., Jarmson, I., Cameron-Ruiz, N., Varjak, M., Pinto, R., Lee, J., Iselin, L., Palmalux, N., Stewart, D., Swingler, S., Greenwood, E., Crozier, T., Gu, Q., Davies, E., Clohisey, S., Wang, B., Costa, F., Santana, M., Ferreria, L., Murphy, L., Fawkes, A., Meynert, A., Grimes, G., ISARIC4C Investigators, Filho, J., Marti, M., Hughes, J., Stanton, R., Wang, E., Ho, A., Davis, I., Jarrett, R., Castello, A., Robertson, D., Semple, M., Openshaw, P., Palmarini, M., Lehner, P., Baillie, J., Rihn, S. & Wilson, S. 2021, 'A prenylated dsRNA sensor protects against severe COVID-19', Science. https://doi.org/10.1126/science.abj3624