These data show that mA3 deamination can have a major impact on the genomic integrity of <i>Mtvs</i>, and that mA3 is actively evolving within this single mouse species suggestive of high-impact genetic conflicts over a short evolutionary time frame.IMPORTANCEThe antiviral cytidine deaminase Apobec3 (apolipoprotein B editing complex 3) mutates retroviral DNA copies generated during new infections. The gene discussed is PNMA3; the disease is infection.