Human APOBEC3G (A3G) and APOBEC3F (A3F) inhibit the replication of Vif-deficient 
human immunodeficiency virus type 1 (HIV-1). HIV-1 Vif overcomes these host 
restriction factors by binding to them and inducing their degradation. Thus, the 
Vif-A3G and Vif-A3F interactions are attractive targets for antiviral drug 
development, as inhibiting these interactions could allow the host defense 
mechanism to control HIV-1 replication. Recently, it has been reported that 
amino acids 105 to 156 of A3G are involved in the interaction with Vif; however, 
to date, the region of A3F involved in Vif binding has not been identified. 
Using our previously reported Vif mutants that are capable of binding to only 
A3G (3G binder) or only A3F (3F binder), in conjunction with a series of A3G-A3F 
chimeras, we have now mapped the APOBEC3-Vif interaction domains. We found that 
the A3G domain that interacts with the Vif YRHHY region is located between amino 
acids 126 and 132 of A3G, which is consistent with the conclusions reported in 
previous studies. The A3F domain that interacts with the Vif DRMR region did not 
occur in the homologous domain but instead was located between amino acids 283 
and 300 of A3F. These studies are the first to identify the A3F domain that 
interacts with the Vif DRMR region and show that distinct domains of A3G and A3F 
interact with different Vif regions. Pharmacological inhibition of either or 
both of these Vif-A3 interactions should prevent the degradation of the APOBEC3 
proteins and could be used as a therapy against HIV-1.