Figure 1

The complexities of the pro- and anti-HIV actions of APOBEC3G. Cross section into the cytoplasm of an infected CD4⁺ T cell is shown, with A3G (yellow) bound to the minus strand ssDNA of the viral genome (white). Virus is shown as green (fit virus) or red (unfit virus) circles forming within and budding out of the infected T cell. Each viral particle contains two copies of the RNA genome and multiple copies of A3G (rods). On the outside of the infected T cell, a cytotoxic CD8⁺ T cell (CTL) is shown recognizing a viral epitope in the context of MHC class I on the surface of the infected T cell. Arrows depict several possible outcomes of A3G action: (1) the classic mode of A3G action as an innate host defense agent whereby it generates mutations in the viral genome resulting in less fit or deactivated virions (red); (2) some low level mutations by A3G that may result in the production of more fit virions (green); (3) A3G may induce mutations in the viral genome that result in drug resistance, as shown by the emergence of more fit virions (green) through the pool of cytoplasmic drug (yellow dots); (4) the process of purifying selection wherein a heavy mutation load on the viral genome is filtered out throughout various stages in the viral life-cycle, resulting in selection for a final pool of viruses with low level mutations that may enhance viral fitness; (5) the mutations generated by A3G may result in the alteration of MHC class I-restricted viral peptide epiotpes such that recognition by CTL is abboragated (A3G-mutated CTL escape epitopes that result in the cloaking of the infected cell from the CTL response are shown in green while wild-type CTL epitopes that result in the recognition and killing of the infected cell are shown in red); (6) the virion infectivity factor (Vif) of HIV (purple) binds cytoplasmic A3G marking it for degredation; and (7) cytoplasmic A3G is trapped in high-molecular-mass (HMM) ribonuclear complexes and consequently rendered ineffective.