Open AccessImpact of ADAR-induced editing of minor viral RNA populations on replication and transmission of SARS-CoV-2
Author(s) -
Johan Ringlander,
Joshua Fingal,
Hanna Kann,
Kasthuri Prakash,
Gustaf E. Rydell,
Maria Andersson,
Anna Martner,
Magnus Lindh,
Peter Horal,
Kristoffer Hellstrand,
Michael Kann
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2112663119
Subject(s) - adar , biology , virology , rna , viral replication , population , nonsynonymous substitution , rna editing , mutation , genetics , virus , gene , medicine , genome , environmental health
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.