Virology

Keeping Your Enemies Close

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Science  28 Oct 2005:
Vol. 310, Issue 5748, pp. 591
DOI: 10.1126/science.310.5748.591b

The immune system's battle with the human immunodeficiency virus is now a familiar one, yet an equally important struggle takes place between host and virus within the cell. In particular, the cellular antiviral factors belonging to the APOBEC3 family of cytidine deaminases impair provirus function by peppering the viral genome with unwanted mutations through the replacement of guanine with adenine (G → A). To protect itself, HIV-1 has evolved a protein (Vif) that binds to and directs the degradation of APOBEC3G and APOBEC3F.

By scrutinizing viral sequences derived from patients and short-term viral isolates, Simon et al. identified naturally arising variants of the HIV vif gene at significant frequency. Some of these mutations caused loss of Vif activity, whereas others modified its function. Correspondingly, provirus sequences from certain individuals with Vif variation carried patterns of G → A replacement that were consistent with activity of APOBEC3G. In other cases, APOBEC3F or both enzymes appeared to be active in generating HIV mutations, suggesting that Vif variants were mediating partial and distinct inhibitory effects on APOBEC3 activity. Thus, rather than simply silencing the APOBEC3 proteins altogether, variation in Vif may allow it to employ the assistance of host factors in increasing viral sequence diversity within an infected individual. — SJS

PLoS Pathog. 1, 20 (2005).

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