Impact of ADAR-induced editing of minor viral RNA populations on replication and transmission of SARS-CoV-2
| Autor: | Johan Ringlander, Joshua Fingal, Hanna Kann, Kasthuri Prakash, Gustaf Rydell, Maria Andersson, Anna Martner, Magnus Lindh, Peter Horal, Kristoffer Hellstrand, Michael Kann |
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| Rok vydání: | 2022 |
| Předmět: |
Adult
Male Adenosine Guanine Adenosine Deaminase viruses Genome Viral Humans Point Mutation Aged Aged 80 and over Sweden Multidisciplinary Virulence SARS-CoV-2 COVID-19 RNA-Binding Proteins Middle Aged Viral Load Amino Acid Substitution Deamination Host-Pathogen Interactions Spike Glycoprotein Coronavirus RNA Viral Female Genetic Fitness RNA Editing Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 119 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2112663119 |
| Popis: | Significance Viral RNA may be edited by enzymes of the ADAR family that deaminate adenosine residues with ensuing A→G mutations. We found multiple A→G mutations in minor viral populations of the SARS-CoV-2 genome. A→G mutations accumulated in the receptor binding domain of the spike gene, which may cause structural changes by altering binding to the ACE2 receptor. Presence of A→G mutations in minor viral populations was associated with reduced viral load, implying that ADAR may limit viral replication. Analyses of >250,000 European samples from 2020 revealed that A→G mutations in SARS-CoV-2 RNA were inversely correlated with mortality as a reflection of incidence. ADAR may thus be important in providing new variants of SARS-CoV-2 with altered infectivity and transmissibility. |
| Databáze: | OpenAIRE |
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