Impact of ADAR-induced editing of minor viral RNA populations on replication and transmission of SARS-CoV-2
Johan Ringlander, Joshua Fingal, Hanna Kann, Kasthuri Prakash, Gustaf E. Rydell, Maria Andersson, Anna Martner, Magnus Lindh, Peter Horal, Kristoffer Hellstrand, Michael Kann
Abstract
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.