( t HIV-infected patients around the worl...) Gladstone investigators discover how resting T cells avoid HIV infection

Four years ago, HIV biologists were galvanized by the discovery of A3G as a potent anti-HIV factor. Initially, scientists thought that A3G had to squeeze into new HIV viral particles in order to produce its antiviral effects. The new Nature study indicates that this is not the case in resting T-cells. The Greene lab showed that in activated T cells, however, Vif, one of HIV's nine genes, counters the antiviral effect of A3G by binding to it and accelerating its destruction as well as decreasing is production. These effects of Vif were so complete that no A3G was left in infected activated CD4 T for incorporation into the new viral particles. Thus, this antiviral action of A3G that only occurs in activated T-cells can be overcome by Vif.

The results have launched the search for a new class of antiviral drugs that block the action of Vif, which would leave A3G poised and able to unleash its antiviral effect from inside viral particles. In resting T cells, though, HIV is defenseless against A3G, because there is no Vif in the incoming viral particles and the virus has not advanced far enough into its life cycle to make new Vif.

The study was supported in part by grants from the National Institutes of Health, the University-wide AIDS Research Program and the American Foundation for AIDS Research.

Other co-authors of the Nature paper, "Cellular APOBEC3G restricts HIV-1 infection in resting CD4 T cells," at the Gladstone Institute of Virology and Immunology are Vanessa B. Soros, Jason F. Kreisberg, Kim Stopak, and Wes Yonemoto. Kreisberg and Stopak are students in the UCSF Biomedical Sciences Graduate Program.

The Gladstone Institute of Virology and Immunology is one of three research institutes of The J. David Gladstone Institutes, an independent, nonprofit biomedical research institution affiliated with UCSF. For further information, visit www.gladstone.ucsf.edu.