HIV-1 NEF PROTEIN CAUSES DEATH IN STRESSED YEAST-CELLS DUE TO DETERMINANTS NEAR THE N-TERMINUS AND ELSEWHERE IN NEF

The Human Immunodeficiency Virus type I (HIV-1) Nef protein is essenti al for AIDS pathogenesis. In order to determine more about the effects of Nef on basic cellular functions Nef was produced in yeast under a variety of conditions and in multiple cell types. Production of Nef ca used cell death in acutely copper- or heat-stressed diploid cells. The N-terminal melittin-like region of Nef was involved in toxicity since a Trp5-->Ala change within Nef change caused increased toxicity. Howe ver, another determinant was also involved in toxicity since productio n of Nef(20)-(206) was also still toxic. In each of these Nef-producin g cells there was coincident membrane permeabilisation. These results suggest the possibility of a novel yeast bioassay for Nef inhibitors a nd that cells producing high levels of Nef may be selectively killed b y stress.