Potential APOBEC-mediated RNA editing of the genomes of SARS-CoV-2 and other coronaviruses and its impact on their longer term evolution

Members of the APOBEC family of cytidine deaminases show antiviral activities in mammalian cells through lethal editing in the genomes of small DNA viruses, herpesviruses and retroviruses, and potentially those of RNA viruses such as coronaviruses. Consistent with the latter, APOBEC-like directional C-*U transitions of genomic plus-strand RNA are greatly overrepresented in SARS-CoV-2 genome sequences of variants emerging during the COVID-19 pandemic. A C-*U mutational process may leave evolutionary imprints on coronavirus genomes, including extensive homoplasy from editing and reversion at targeted sites and the occurrence of driven amino acid sequence changes in viral proteins. If sustained over longer periods, this process may account for the previously reported marked global depletion of C and excess of U bases in human seasonal coronavirus genomes. This review synthesizes the current knowledge on APOBEC evolution and function and the evidence of their role in APOBEC-mediated genome editing of SARS-CoV-2 and other coronaviruses.

Automated summary

Members of the APOBEC family exhibit antiviral activities in mammalian cells through lethal editing of the genomes of various viruses, including RNA viruses like coronaviruses. APOBEC-like C-*U transitions are significantly overrepresented in the SARS-CoV-2 genome sequences during the COVID-19 pandemic, which may leave evolutionary imprints on coronavirus genomes. This process may lead to homoplasy and amino acid sequence changes in viral proteins, potentially explaining global depletion of C and excess of U bases in human seasonal coronavirus genomes.