However, cell-based studies have indicated that an APOBEC3 protein from a mammal to which the virus has not yet adapted may provide an effective strategy for thwarting species-specific viral counter-defenses. For instance, human APOBEC3G can potently inhibit the replication of SIV (except isolates such as SIV cpz which encode a Vif protein closely related to that of HIV-1), feline foamy virus and MLV (e.g., [17] [18] [19] [20] 25, 26, 39, 41, 42] ). Similarly, mouse APOBEC3 can potently block HIV-1 replication (regardless of Vif), although it is completely unable to impede the replication of MLV [26, 41] . One of the most dramatic examples to date used human and mouse APOBEC3 proteins to inhibit the mobilization of the yeast retrotransposons Ty1 and Ty2 [43, 44] . Thus, it is reasonable to hypothesize that cross-species expression of an APOBEC3 protein may be used to create a powerful barrier to impede or perhaps even block retrovirus infection. Here, this rationale is applied to the specific question of whether human APOBEC3G expression can inhibit the transmission of PERV from pig to human cells. The results demonstrate that PERV transmission can be strongly inhibited by APOBEC3G.