Abstract
Following spillover, viruses must adapt to new selection pressures exerted by antiviral responses in their new hosts. In mammals, cellular defense mechanisms often include viral nucleic acid editing pathways mediated through protein families apolipoprotein-B mRNA-editing complex (APOBEC) and Adenosine Deaminase Acting on ribonucleic acid (ADAR). APOBECs induce C→U transitions in viral genomes; the APOBEC locus is highly polymorphic with variable numbers of APOBEC3 paralogs and target preferences in humans and other mammals. APOBEC3 paralogs have shaped the evolutionary history of human immunodeficiency virus, with compelling bioinformatic evidence also for its mutagenic impact on monkeypox virus and severe acute respiratory syndrome coronavirus 2. ADAR-1 induces adenose-to-inosine (A→I) substitutions in double-stranded ribonucleic acid (RNA); its role in virus adaptation is less clear, as are epigenetic modifications to viral genomes, such as methylation. Nucleic acid editing restricts evolutionary space in which viruses can explore and may restrict viral-host range.