In the human genome the apolipoprotein B mRNA-editing enzyme catalytic 
polypeptide (APOBEC)3 gene has expanded into a tandem array of genes termed 
APOBEC3A-G. Two members of this family, APOBEC3G and APOBEC3F, have been found 
to have potent activity against virion infectivity factor deficient (Deltavif) 
human immunodeficiency virus 1 (HIV-1). These enzymes become encapsidated in 
Deltavif HIV-1 virions and in the next round of infection deaminate the newly 
synthesized reverse transcripts. The lentiviral Vif protein prevents the 
deamination by inducing the degradation of APOBEC3G and APOBEC3F. We report here 
that two additional APOBEC3 family members, APOBEC3B and APOBEC3C, have potent 
antiviral activity against simian immuno-deficiency virus (SIV), but not HIV-1. 
Both enzymes were encapsidated in HIV-1 and SIV virions and were active against 
Deltavif SIV(mac) and SIV(agm). SIV Vif neutralized the antiviral activity of 
APOBEC3C, but not that of APOBEC3B. APOBEC3B induced abundant G --> A mutations 
in both wild-type and Deltavif SIV reverse transcripts. APOBEC3C induced 
substantially fewer mutations. APOBEC3F was found to be active against SIV and 
sensitive to SIV(mac) Vif. These findings raise the possibility that the 
different APOBEC3 family members function to neutralize specific lentiviruses.