APOBECs and their role in proviral DNA synthesis

The human APOBEC3 subfamily consists of seven DNA cytosine deaminases that act on single-stranded cDNA during HIV reverse transcription. The net effect of these enzymes is the restriction of viral infectivity due to the inhibition of reverse transcription and to the hypermutation of those genomes that complete cDNA synthesis and integration. In this chapter, we introduce the APOBEC3 proteins in historical context as a prelude to the consideration of evidence for their deaminase-dependent and deaminase-independent mechanisms of antiviral action. We also consider how editing of the viral genome by APOBEC3 proteins may alter the coding capacity and pathogenic potential of HIV by contributing to the inherently error-prone replication process and to the overall high level of HIV genetic variation.