Since the identification of APOBEC3G (A3G) as a potent restriction factor of 
HIV-1, a tremendous amount of effort has led to a broadened understanding of 
both A3G and the APOBEC3 (A3) family to which it belongs. In spite of the 
fine-tuned viral counterattack to A3 activity, in the form of the HIV-1 Vif 
protein, enthusiasm for leveraging the Vif : A3G axis as a point of clinical 
intervention remains high. In an impressive explosion of information over the 
last decade, additional A3 family members have been identified as antiviral 
proteins, mechanistic details of the restrictive capacity of these proteins have 
been elucidated, structure-function studies have revealed important molecular 
details of the Vif : A3G interaction, and clinical cohorts have been scrutinized 
for correlations between A3 expression and function and viral pathogenesis. In 
the last year, novel and unexpected findings regarding the role of A3G in 
immunity have refocused efforts on exploring the potential of harnessing the 
natural power of this immune defense. These most recent reports allude to 
functions of the A3 proteins that extend beyond their well-characterized 
designation as restriction factors. The emerging story implicates the A3 family 
as not only defense proteins, but also as participants in the broader innate 
immune response.