@article{Wickenhagen_A-2021_45007,
title = {A prenylated dsRNA sensor protects against severe COVID-19},
author = {Wickenhagen, A. and Sugrue, E. and Lytras, S. and Kuchi, S. and Noerenberg, M. and Turnbull, M. and Loney, C. and Herder, V. and Allan, J. and Jarmson, I. and Cameron-Ruiz, N. and Varjak, M. and Pinto, R. and Lee, J. and Iselin, L. and Palmalux, N. and Stewart, D. and Swingler, S. and Greenwood, E. and Crozier, T. and Gu, Q. and Davies, E. and Clohisey, S. and Wang, B. and Costa, F. and Santana, M. and Ferreria, L. and Murphy, L. and Fawkes, A. and Meynert, A. and Grimes, G. and ISARIC4C Investigators and Filho, J. and Marti, M. and Hughes, J. and Stanton, R. and Wang, E. and Ho, A. and Davis, I. and Jarrett, R. and Castello, A. and Robertson, D. and Semple, M. and Openshaw, P. and Palmarini, M. and Lehner, P. and Baillie, J. and Rihn, S. and Wilson, S.},
month = {sep},
year = {2021},
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.},
journal = {Science},
publisher = {American Association for the Advancement of Science},
url = {https://doi.org/10.1126/science.abj3624},
}
