HIV LTR-dependent expression of Bax selectively induces apoptosis in Tat-positive cells.
HIV integrates into the host cell genome where it persists for the life of the cell. One approach to reducing viral burden is to selectively eliminate cells containing integrated provirus early following infection. We have used the HIV LTR promoter to selectively express transgenes in human cells positive for the HIV transactivator protein Tat. Transient transfection of Jurkat cells, or Jurkat cells stably expressing Tat (Jurkat-Tat), with a LTR construct containing luciferase reporter gene resulted in a 37-fold increase in gene expression when Tat was present. We have demonstrated that when pro-apoptotic Bax was used as the transgene, cytotoxicity was seen only in the Jurkat-Tat cells. Annexin-V staining indicated that Bax induced cell death by apoptosis. In mixed populations of Jurkat and Jurkat-Tat cells, the LTR-Bax construct was selectively cytotoxic to the Tat-positive cells. These results suggest that Bax under the control of the HIV LTR can be used to destroy cells harbouring HIV without affecting uninfected cells.
McCoubrie
Joanne E
JE
Laboratory for Cancer Medicine, Western Australian Institute for Medical Research, Royal Perth Hospital, Perth, WA 6000, Australia.
Kendrick
Tulene S
TS
Minchin
Rodney F
RF
D017209:Apoptosis / Q000235:genetics*; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism*; D041722:Genes, Transgenic, Suicide / Q000235:genetics*; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D011401:Promoter Regions, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D015696:Gene Products, tat; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein