STUDIES OF HIV-2 PROMOTER ACTIVITY AND CELL-SPECIFIC ABLATION

We have a developed a retroviral mediated molecular ablation method to specifically eliminate HIV Tat-expressing cells. This approach utiliz es the Tat-inducible HIV-2 promoter and a conditional toxin gene. The Herpes Simplex Virus thymidine kinase gene product is toxic to mammali an cells only after treatment with Ganciclovir (GCV) or other nucleosi de analogues. We demonstrate here that certain promoter modifications can decrease basal expression while retaining the ability to be transa ctivated. Furthermore, we show that a HIV-2 promoter thymidine kinase gene cassette transduced via retroviral vectors into tissue culture ce lls can specifically promote the ablation of HIV-Tat expressing cells in the presence GCV. We also show that there is a large differential i n HIV-thymidine kinase gene transcription and lethal drug dose between Tat-expressing cells and Tat-negative cells.