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 utilizes the Tat-inducible HIV-2 promoter and a conditional toxin gene. The Herpes Simplex Virus thymidine kinase gene product is toxic to mammalian cells only after treatment with Ganciclovir (GCV) or other nucleoside analogues. We demonstrate here that certain promoter modifications can decrease basal expression while retaining the ability to be transactivated. Furthermore, we show that a HIV-2 promoter thymidine kinase gene cassette transduced via retroviral vectors into tissue culture cells can specifically promote the ablation of HIV-Tat expressing cells in the presence GCV. We also show that there is a large differential in HIV-thymidine kinase gene transcription and lethal drug dose between Tat-expressing cells and Tat-negative cells.
Brady
H J
HJ
Laboratory of Gene Structure and Expression, National Institute for Medical Research, Mill Hill, London, U.K.
Miles
C G
CG
Pennington
D J
DJ
Dzierzak
E A
EA
D001483:Base Sequence; D017353:Gene Deletion; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism*; D015756:Genes, tat / Q000235:genetics*; D015498:HIV-2 / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics*; D014162:Transfection; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus; D013937:Thymidine Kinase