Cytosine deaminases of the APOBEC enzyme family act as host restriction factors by targeting retroviruses. Humans express multiple APOBEC proteins, whereas mice express only APOBEC A3 (mA3A). In PLoS Pathogens, Stavrou et al. develop transgenic mA3A-deficient mice that express either human APOBEC3A (hA3A) or human APOBEC3G (hA3G) to assess the physiological antiretroviral roles of these enzymes in isolation. Transgenic mice expressing either hA3A or hA3G control retroviral infection better than wild-type or mA3A-deficient mice do; however, the mechanism differs for each. hA3G is packaged in virions in which extension cytosine deamination is evident, as is inhibition of viral reverse-transcriptase activity. In contrast, hA3A is not packaged in virions and does not inhibit viral reverse transcriptase; however, the exact mode of hA3A-mediated restriction of virus remains uncertain. Nevertheless, this system might facilitate the physiological analysis of wild-type and mutant APOBEC at various stages of retroviral infection.

PLoS Pathogens (22 May 2014) doi:10.1371/journal.ppat.1004145