Prototype Foamy Virus Bet Impairs the Dimerization and Cytosolic Solubility of Human APOBEC3G
Cellular cytidine deaminases from the APOBEC3 family are potent restriction factors able to block the replication of retroviruses. Consequently, retroviruses have evolved a variety of different mechanisms to counteract inhibition by APOBEC3 proteins. Lentiviruses such as Human immunodeficiency virus (HIV) express Vif that interferes with APOBEC3 proteins by targeting the restriction factors for proteasomal degradation, hence blocking their ability to access the reverse transcriptase complex in the virions. Other retroviruses use less well characterized mechanisms to escape APOBEC3s' mediated cellular defence. Here we show that Prototype foamy virus Bet can protect foamy viruses and an unrelated simian immunodeficiency virus against human APOBEC3G (A3G). In our system, Bet binds to A3G and prevents its encapsidation without inducing its degradation. Bet failed to co-immunoprecipitate with A3G mutants unable to form homodimers, and dramatically reduced the recovery of A3G proteins from soluble cytoplasmic cell fractions. The Bet - A3G interaction is probably a direct binding and seems to be independent of RNA. Together, this data suggest a novel model whereby Bet uses two possibly complementary mechanisms to counteract A3G: (1) Bet prevents encapsidation of A3G by blocking A3G dimerization, and (2) sequesters A3G in immobile complexes, impairing its ability to interact with nascent virions.