A prenylated dsRNA sensor protects against severe COVID-19.
Science
; 374(6567): eabj3624, 2021 Oct 29.
Article
en En
| MEDLINE
| ID: mdl-34581622
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 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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
2',5'-Oligoadenilato Sintetasa
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ARN Bicatenario
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ARN Viral
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SARS-CoV-2
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COVID-19
Límite:
Animals
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Humans
Idioma:
En
Revista:
Science
Año:
2021
Tipo del documento:
Article
País de afiliación:
Reino Unido