Successful intracellular pathogens must evade or neutralize the innate immune 
defenses of their host cells and render the cellular environment permissive for 
replication. For example, to replicate efficiently in CD4(+) T lymphocytes, 
human immunodeficiency virus type 1 (HIV-1) encodes a protein called viral 
infectivity factor (Vif) that promotes pathogenesis by triggering the 
degradation of the retrovirus restriction factor APOBEC3G. Other APOBEC3 
proteins have been implicated in HIV-1 restriction, but the relevant repertoire 
remains ambiguous. Here we present the first comprehensive analysis of the 
complete, seven-member human and rhesus APOBEC3 families in HIV-1 restriction. 
In addition to APOBEC3G, we find that three other human APOBEC3 proteins, 
APOBEC3D, APOBEC3F, and APOBEC3H, are all potent HIV-1 restriction factors. 
These four proteins are expressed in CD4(+) T lymphocytes, are packaged into and 
restrict Vif-deficient HIV-1 when stably expressed in T cells, mutate proviral 
DNA, and are counteracted by HIV-1 Vif. Furthermore, APOBEC3D, APOBEC3F, 
APOBEC3G, and APOBEC3H of the rhesus macaque also are packaged into and restrict 
Vif-deficient HIV-1 when stably expressed in T cells, and they are all 
neutralized by the simian immunodeficiency virus Vif protein. On the other hand, 
neither human nor rhesus APOBEC3A, APOBEC3B, nor APOBEC3C had a significant 
impact on HIV-1 replication. These data strongly implicate a combination of four 
APOBEC3 proteins--APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H--in HIV-1 
restriction.