Our data indicate that the engineering of pigs to express human APOBEC3G (or an equally potent non-porcine APOBEC3) may result in animals whose cells and tissues are much less likely to disseminate functional PERV. The deamination-independence of the restriction mechanism suggests that a catalytically inert APOBEC3G protein, such as E259Q, may be equally potent and simultaneously reduce the risk of cancer-promoting mutagenesis. APOBEC3G or APOBEC3G-E295Q expressing pigs may therefore constitute safer source animals for pig-to-human xenotransplantation procedures. In contrast to knockdown, knockout (by gene targeting or selective breeding) or most chemical-based anti-viral approaches to neutralize PERV [15] , the APOBEC3 antiviral defense system has several advantages including a potentially broad neutralizing activity (effective against PERV and likely several other endogenous and exogenous viruses) and an applicability to situations where many copies of a virus are already present in a genome. Analogous transgenic applications can be envisaged, such as using cross-species APOBEC3 expression to purposefully impede known viruses (e.g., the AIDS virus HIV-1 or the Hepatitis B virus HBV). Moreover, for humans and other mammals with multiple APOBEC3 proteins, our data encourage the development of methods to induce/up-regulate endogenous APOBEC3 proteins, which have the capacity but may not normally restrict a particular virus (e.g., human APOBEC3B and HIV-1).