Abstract
The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3/A3) family of cytosine deaminases serves as a key innate immune barrier against invading retroviruses and endogenous retroelements. The A3 family's restriction activity against these parasites primarily arises from their ability to catalyze cytosine-to-uracil conversions, resulting in genome editing and the accumulation of lethal mutations in viral genomes. Additionally, non-editing mechanisms, including deaminase-independent pathways, such as blocking viral reverse transcription, have been proposed as antiviral strategies employed by A3 family proteins. Although viral factors can influence infection progression, the determinants that govern A3-mediated restriction are critical in shaping retroviral infection outcomes. This review examines the interactions between retroviruses, specifically human immunodeficiency virus type 1 and human T-cell leukemia virus type 1, and A3 proteins to better understand how editing and non-editing activities contribute to the trajectory of these retroviral infections.