Mangeat B, Turelli P, Caron G, et al. Nature. 2003;424:99–102
Purpose of the Study.
Innate intracellular antiretroviral defense mechanisms have been described. Viral infection requires that these lines of defense be overcome, and this task is usually accomplished by specialized viral proteins. The virus infectivity factor (Vif) protein of human immunodeficiency virus (HIV) is required to counter the antiviral activity of a protein expressed in human T cells, ie, APOBEC3G (apolipoprotein B messenger RNA-editing enzyme, catalytic polypeptide-like 3G, which is also known as CEM15). APOBEC3G family members have potent DNA-editing activity, triggering hypermutation in nascent DNA. The purpose this study was to examine potential mechanisms of APOBEC3G effects.
In in vitro experiments, the investigators measured the infectivity of wild-type and vif-deleted virions, in the presence or absence of APOBEC3G. They then tested a series of point mutations, concentrating on residues of the catalytic site of APOBEC3G.
When produced in the presence of APOBEC3G, Vif-defective virus was not infectious. The results of these studies demonstrated that APOBEC3G exerts its antiviral effects during reverse transcription, triggering lethal guanosine-to-adenosine hypermutation in the complementary retroviral DNA. It was also noted that APOBEC3G could act on a broad range of retroviruses, in addition to HIV.
APOBEC3G exerts its anti-HIV activity through lethal editing of DNA reverse transcripts.
Immune cells have evolved a remarkable set of mechanisms to defend against microbial invaders, and microbes have coevolved to circumvent these defenses. APOBEC3G is a human factor produced in T cells that inherently inactivates retroviruses. However, as shown in this study, the HIV accessory protein Vif selectively inactivates APOEBEC3G. An understanding of the mechanisms of viral infectivity and resistance has generated an increasing number of targets for interventions against HIV infection. For example, strategies aimed at limiting the activity of Vif might allow APOBEC3G to better accomplish its task of virus suppression.