A prenylated dsRNA sensor protects against severe COVID-19

Wickenhagen, Arthur, Sugrue, Elena, Lytras, Spyros, Kuchi, Srikeerthana, Noerenberg, Marko, Turnbull, Matthew L, Loney, Colin, Herder, Vanessa, Allan, Jay, Jarmson, Innes
et al (show 38 more authors) (2021) A prenylated dsRNA sensor protects against severe COVID-19. SCIENCE, 374 (6567). eabj3624-.

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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.

Item Type: Article
Uncontrolled Keywords: ISARIC4C Investigators, Animals, Chiroptera, Humans, Coronaviridae, Endoribonucleases, Phosphoric Diester Hydrolases, Isoenzymes, 2',5'-Oligoadenylate Synthetase, Interferons, Retroelements, RNA, Double-Stranded, 5' Untranslated Regions, RNA, Viral, Severity of Illness Index, Virus Replication, Polymorphism, Single Nucleotide, Protein Prenylation, A549 Cells, COVID-19, SARS-CoV-2
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 01 Oct 2021 07:01
Last Modified: 18 Jan 2023 21:27
DOI: 10.1126/science.abj3624
Open Access URL: https://doi.org/10.1126/science.abj3624
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3138818