The nef gene product of HIV has been reported to down-regulate viral growth by suppressing viral transcription and to possess biochemical properties similar to G-proteins. These genetic and biochemical features of nef have led to a hypothesis that nef plays a central role in the regulation of viral gene expression and that nef is somehow involved in the establishment and/or maintenance of latency during viral pathogenesis. However recent reports, including ours, have challenged such a negative role for nef in viral growth, weakening the basis of such a hypothesis. This proposal is an attempt to investigate more fully the molecular and biochemical properties of nef and also to explore its possible in vivo function(s).