[6][7][8][9][10][11][12][13] APOBEC3G exerts innate antiretroviral immune activity against retroviruses, most notably HIV, by interfering with proper replication.

However, lentiviruses such as HIV have evolved the Viral infectivity factor (Vif) protein in order to counteract this effect.

However, unlike the typical cytidine deaminases, APOBEC3G contains a unique alpha helix between two beta sheets in the catalytic domain that could be a cofactor binding site.

[20] The D128 amino acid residue, which lies within CD1 (Figure 1), appears to be particularly important for APOBEC3G interactions with Vif because a D128K point mutation prevents Vif-dependent depletion of APOBEC3G.

[22][23] Additionally, amino acids 128–130 on APOBEC3G form a negatively charged motif that is critical for interactions with Vif and the formation of APOBEC3G-Vif complexes.

The predicted deamination reaction is driven by a direct nucleophilic attack on position 4 of the cytidine pyrimidine ring by the zinc-coordinated enzyme.

[29] However, this has been discounted because human APOBEC3G reduces viral cDNA levels independently of DNA repair enzymes UNG and SMUG1.

[29] It is predicted that reverse transcription is also negatively affected by APOBEC3G binding to viral RNA and causing steric alterations.

[18] APOBEC3G was associated with interference of viral DNA integration into the host genome in a manner dependent on functional catalytic domains and deaminase activity.

Xu et al. conducted studies with PBMC cells and found that, in the absence of Vif, 7±4 APOBEC3G molecules were incorporated into the virions and resulted in potent inhibition of HIV-1 replication.

However, Vif counteracts this antiretroviral factor, enabling production of viable and infective HIV-1 virions in the presence of APOBEC3G activity .

[39] Such sublethal mutagenesis contributes to greater genetic diversity among the HIV-1 virus population, demonstrating the potential for APOBEC3G to enhance HIV-1's ability to adapt and propagate.