We have established a quantitative assay to monitor the zoonotic transmission of PERV to human 293T cells. Expression of human APOBEC3G in the pig PK-15 cell line strongly inhibited PERV zoonoses, while the endogenous APOBEC3F protein of pigs appeared considerably less effective. These data are the first to show that human APOBEC3G can inhibit PERV and the first to demonstrate that APOBEC3 proteins can be used purposefully to reduce if not prevent zoonotic retroviral infections. These results were not anticipated because human APOBEC3G has a relatively weak effect against the PERV-related gamma-retrovirus MLV [26, 39] .