Human APOBEC3G and other APOBEC3 cytidine deaminases inhibit a variety of 
retroviruses, including Vif-deficient HIV-1. These host proteins are packaged 
into viral particles and inhibit the replication of virus in new target cells. 
A3G and A3F are known to be efficiently packaged into HIV-1 virions by binding 
to 7SL RNA through the Gag NC domain; however, the packaging mechanisms of other 
APOBEC3 proteins are poorly defined. We have now demonstrated that APOBEC3C 
(A3C) can be efficiently packaged into HIV-1 virions that are deficient for 
viral genomic RNA. Inhibition of the encapsidation of 7SL RNA into HIV-1 virions 
blocked the packaging of A3G, but not A3C. While the NC domain is required for 
efficient packaging of A3G, deletion of this domain had little effect on A3C 
packaging into HIV-1 Gag particles. A3C interacted with HIV-1 Gag which was MA 
domain-dependent and RNA-dependent. Deletion of the MA domain of HIV-1 Gag 
inhibited A3C but not A3G packaging into HIV-1 Gag particles. Thus, A3G and A3C 
have evolved to use distinct mechanisms for targeting retroviruses.