Leveraging APOBEC3 proteins to alter the HIV mutation rate and combat AIDS

Abstract

At least two human APOBEC3 proteins – APOBEC3F and APOBEC3G – are capable of inhibiting HIV-1 replication by mutation of the viral cDNA. HIV-1 averts lethal restriction through its accessory protein Vif, which targets these APOBEC3 proteins for proteasomal degradation. The life-or-death interaction between human APOBEC3 proteins and HIV-1 Vif has stimulated much interest in developing novel therapeutics aimed at altering the deaminase activity of the APOBEC3s, thus changing the virus’ mutation rate to either lethal or suboptimal levels. The current state of mechanistic information is reviewed and the possible risks and benefits of increasing (via hypermutation) or decreasing (via hypomutation) the HIV-1 mutation rate through APOBEC3 proteins are discussed.