The approach of this project is to design vectors which will be specifically expressed in cells infected with retroviruses and kill the cells. The approach takes advantage of the fact that these viruses express unique regulatory proteins which can be used as specific activators of the suicide vectors. The suicide vectors utilize the herpes thymidine kinase (HSV-TK) enzyme which converts the drug gangcyclovir to a toxic metabolite. The HSV-TK gene is expressed under the regulatory control of the viral long terminal repeats (LTRs) which will respond to the presence of the transacting proteins Tat or Tax in HIV- or HTLV-I-infected cells and produce the HSV-TK product. Upon addition of gangcyclovir, the cells should die. Current work involves the use of new vectors for targeting HIV or HTLV-I susceptible cells, establishing cell lines which stably contain the suicide vectors, studying the sensitivity of these cell lines to viral infection and titrations of drug response, and sensitivity to retroviral infection. Experiments in mice will be performed as in vivo tests of these systems which may eventually prove useful for human gene therapy.
