A cell suicide vector has been devised which makes a cell susceptible to the toxic effects of gangcyclovir when infected with HIV. The thymidine kinase (TK) gene of herpes simplex virus (HSV) converts gangcyclovir to a toxic metabolite, which is lethal to a cell containing the HSV-TK gene. The expression of the HSV-TK gene has been placed under the regulatory control of the HIV-LTR. This hybrid gene will become transcriptionally activated upon infection with HIV through the transactivation of the HIV- LTR by the Tat protein produced by the infecting HIV virus. When exposed to gangcyclovir, these cells will die, presumably without the ability to package virus to infect other cells. Similar strategies exist for HTLV-I. Work focuses on designing vectors which maintain the ability to function well with the HSV-TK insert. Upon successful establishment of cell lines containing these constructs, extensive studies regarding the sensitivity of these cells to viral infection and drug response will be completed. In vivo experiments using SCID mice and vectors for human gene therapy are the ultimate goals of these experiments.
