The end of HIV-1 budding machinery

HIV-1 reprograms the cellular machinery and employs several unknown host proteins to bud from infected cells. In 5 October Cell, Jennifer Garrus and colleagues from University of Utah School of Medicine and Myriad Genetics, Salt Lake City show that the human tumor susceptibility gene 101 (Tsg101), which functions in vacuolar protein sorting (Vps) pathway, is critical to HIV-1 budding and the progression of the disease into full-blown AIDS.

Garrus et al. used small interfering RNA to stop production of Tsg101 in HIV infected human embryonic kidney cells lines. They found that Tsg101 depletion stopped HIV-1 replication at a late stage of the budding process. When they re-introduced Tsg101 in these cells, HIV-1 budding resumed. In addition, they showed that dominant negative mutant Vps4 proteins that inhibit vacuolar protein sorting also arrest HIV-1 budding (Cell 2001, 107:55-65).

New AIDS drugs that inactivate the Tsg101 protein may limit...