A Prenylated dsRNA Sensor Protects Against Severe COVID-19 and is Absent in Horseshoe Bats
A Prenylated dsRNA Sensor Protects Against Severe COVID-19 and is Absent in Horseshoe Bats
Abstract Cell autonomous antiviral defenses can inhibit the replication of viruses and reduce transmission and disease severity. To better understand the antiviral response to SARS-CoV-2, we used interferon-stimulated gene (ISG) expression screening to reveal that OAS1, through RNase L, potently inhibits SARS-CoV-2. We show that while some people can express a prenylated OAS1 variant, that is membrane-associated and blocks SARS-CoV-2 infection, other people express a cytosolic, nonprenylated OAS1 variant which does not detect SARS-CoV-2 (determined by the splice-acceptor SNP Rs10774671). Alleles encoding nonprenylated OAS1 predominate except in people of African descent. 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. Remarkably, approximately 55 million years ago, retrotransposition ablated the OAS1 prenylation signal in horseshoe bats (the presumed source of SARS-CoV-2). Thus, SARS-CoV-2 never had to adapt to evade this defense. As prenylated OAS1 is widespread in animals, the billions of people that lack a prenylated OAS1 could make humans particularly vulnerable to the spillover of coronaviruses from horseshoe bats.
Kuchi Srikeerthana、Allan Jay、Jarmson Innes、Cameron-Ruiz Natalia、Varjak Margus、Stewart Douglas G、Greenwood Edward J D、Crozier Thomas W M、Santana Monique Freire、ISARIC4C investigators、Stanton Richard J、Wang Eddie C Y、Ho Antonia、Baillie Kenneth、Jarrett Ruth F、Robertson David L、Rihn Suzannah J、Wilson Sam J、Turnbull Matthew L、de Lima Ferreira Luiz Carlos、Herder Vanessa、Lytras Spyros、Lehner Paul J、Sugrue Elena、Castello-Palomares Alfredo、Wang Bo、Wickenhagen Arthur、Gu Quan、Palmarini Massimo、Da Silva Filho Joao Luiz、Marti Matthias、Clohisey Sara、Noerenberg Marko、Loney Colin、Swingler Simon、Maranh?o Costa Fabio Trindade、Pinto Rute M
基础医学分子生物学微生物学
Kuchi Srikeerthana,Allan Jay,Jarmson Innes,Cameron-Ruiz Natalia,Varjak Margus,Stewart Douglas G,Greenwood Edward J D,Crozier Thomas W M,Santana Monique Freire,ISARIC4C investigators,Stanton Richard J,Wang Eddie C Y,Ho Antonia,Baillie Kenneth,Jarrett Ruth F,Robertson David L,Rihn Suzannah J,Wilson Sam J,Turnbull Matthew L,de Lima Ferreira Luiz Carlos,Herder Vanessa,Lytras Spyros,Lehner Paul J,Sugrue Elena,Castello-Palomares Alfredo,Wang Bo,Wickenhagen Arthur,Gu Quan,Palmarini Massimo,Da Silva Filho Joao Luiz,Marti Matthias,Clohisey Sara,Noerenberg Marko,Loney Colin,Swingler Simon,Maranh?o Costa Fabio Trindade,Pinto Rute M.A Prenylated dsRNA Sensor Protects Against Severe COVID-19 and is Absent in Horseshoe Bats[EB/OL].(2025-03-28)[2025-06-17].https://www.medrxiv.org/content/10.1101/2021.05.05.21256681.点此复制
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