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Background APOBEC3 (A3) cytidine deaminases restrict viral replication by efficiently editing viral genomes. To escape this restriction by lethal mutagenesis, lentiviruses have evolved the viral infectivity factor (Vif), which binds A3 proteins and targets them for proteolytic degradation. In contrast, foamy viruses (FVs) express high amounts of the accessory Bet protein allowing replication in the presence of A3, apparently by A3 binding/sequestration and thus preventing A3 packaging into virus particles. Due to virus-host coevolution, Bet can only counteract the activity of A3s from their cognate host species. FV bet genes appear to be ancient, since corresponding sequences are clearly present in endogenous FV sequences in different mammalian species.

Essential domains and sequences of the foamy virus Bet protein involved in binding and counteracting APOBEC3 restriction factors