Host-Directed editing of SARS-CoV-2 genome: From perspective of host APOBEC and ZAP

Abstract

RNA viruses use CpG reduction to evade the host cell defense, but the driving mechanism is still largely unknown. To address this, we used a rapidly growing genomic dataset of SARS-CoV-2 with relevant metadata information. Remarkably, by simply ordering SARS-CoV-2 genomes by their date of collection, we find a progressive increase of C-to-U substitutions resulting in CpG loss over just a few months. This is consistent with APOBEC-mediated RNA editing resulting in CpG reduction, thus allowing the virus to escape ZAP-mediated RNA degradation. Our results thus link the dynamics of target sequences in the viral genome for two known host molecular defense mechanisms, mediated by the APOBEC and ZAP proteins.