HIV-1 Membrane Fusion: Targets of Opportunity

The AIDS pandemic is spreading unchecked in many parts of the world. Currently available anti-viral regimens are plagued by their high cost, by serious side effects in a significant minority of recipients, and by the increasing problems of drug-resistant HIV variants. Fortunately, rapid advances in understanding how HIV-1 enters cells have lead to the identification of promising new drug targets and have also suggested new strategies for the generation of vaccine candidates. The cellular proteins required for HIV-1 entry have been identified, and structural studies using fragments of the viral envelope protein (Env) that mediates entry have provided views of Env in two conformations. However, placing this information in the appropriate order and kinetic context has not been so straightforward. A paper published in this issue identifies the rate limiting step in Env-mediated membrane fusion and the proximal cause...