Background:  Human APOBEC3G (h3G) inhibits viral infectivity factor (Vif)-deficient HIV-1 by specifically packaging into HIV-1 virions and massively editing the viral DNA during reverse transcription. Vif allows the virus to escape h3G-mediated innate immunity by binding h3G and targeting it for proteasomal degradation. h3G is 1 of 7 human APOBEC3 genes (h3A to h3G), all of which are clustered on chromosome 22.

Methods:  Because many of these additional APOBEC3 genes are similar in sequence to h3G, we sought to further characterize their effects on HIV-1.

Results:  We found that h3B and h3F also exert a strong anti-viral phenotype in the absence of Vif. Unlike h3F and h3G, h3B is resistant to suppression by either HIV-1 or HIV-2 Vif. Surprisingly, we found that all of the hAPOBEC3 proteins, including ones that do not suppress viral infectivity, specifically package into HIV-1 virions and minimal virus like particles. Additionally, a more distantly related protein, hAPOBEC1, also packaged into HIV-1 virions, suggesting that packaging is a general feature of these proteins. In contrast to h3F and h3G, h3B and the weakly antiviral h3C protein failed to bind HIV-1 Vif by co-immunoprecipitation. 

Conclusions:  These data suggest that activation of the endogenous h3B gene could provide protection from HIV-1 in vivo. However, other than in a few highly differentiated cell lines, we have not observed significant expression of h3B mRNA, including in lymphoid tissues where both h3F and h3G are extensively co-expressed.

Keywords: APOBEC; Vif; APOBEC3G