The APOBEC3 (short for “apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like”) family of human cytidine deaminases provides a first line of defense against many exogenous and endogenous retroviruses such as HIV-1 and the retro-element LINE-11–6. APOBEC3 (A3) proteins restrict replication of retroviruses by inducing hypermutations in the viral genome7. A3s deaminate deoxycytidines in ssDNA into uridines during reverse transcription. This results in G to A hypermutations, as adenosines are transcribed across from uridines during second strand DNA synthesis. While all A3 enzymes deaminate deoxycytidines in ssDNA, they have differential substrate specificities that are context dependent, resulting in altered frequencies of mutation for the deoxycytidines. Some A3s deaminate the second deoxycytidine in a sequence containing CC while others deaminate deoxycytidine in a TC context8–10. However, not every cognate dinucleotide motif (CC or TC) in the ssDNA of the HIV genome is deaminated11. Nevertheless, hypermutation in a viral genome results in defective proteins and proviruses, thus decreasing the probability of further viral replication12.