Contribution of APOBEC3-driven mutagenesis to HIV evolution and HIV drug resistance

Sequence variation is central to the ability of HIV-1 to evade immune responses and antiretroviral therapeutics. APOBEC3 editing enzymes are potent mutagens of retroviral genomes. In humans, the APOBEC3 family comprises seven different proteins (APOBEC3A [A3A] to A3H), whose cytidine deaminase activity - if left unchecked - results in extensive mutagenesis of the HIV-1 genome. There is emerging evidence that cytidine deaminases other than A3G play an important role in restricting the spread and replication of HIV-1. APOBEC3 molecules, indeed, differ not only in catalytic activity and expression but also in susceptibility to HIV-1 Vif-mediated degradation. The interplay between these intracellular host defenses and HIV counterstrategies is discussed in this chapter with a special emphasis on viral evolution and drug resistance.