9801796 |
Macreadie I, Sankovich S, Failla P, Lowe M, Curtain C, Castelli L, Azad A: HIV-1 Nef protein causes death in stressed yeast cells due to determinants near the N-terminus and elsewhere in Nef. Biochem Mol Biol Int. 1998 Oct;46(2):277-86. The Human Immunodeficiency Virus type 1 (HIV-1) Nef protein is essential 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 caused 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. However, another determinant was also involved in toxicity since production of Nef20-206 was also still toxic. In each of these Nef-producing cells there was coincident membrane permeabilisation. These results suggest the possibility of a novel yeast bioassay for Nef inhibitors and that cells producing high levels of Nef may be selectively killed by stress. |
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