RESIDUAL EXPRESSION OF REPORTER GENES IN CONSTRUCTS MIMICKING HIV GENOME ORGANIZATION

Plasmids were constructed whereby the expression of a reporter gene, e ither the cDNA corresponding to the secreted form of human alkaline ph osphatase (SEAP) or the herpes simplex virus type 1 (HSV1) thymidine k inase (tk) gene, was rendered dependent upon the expression of the hum an immunodeficiency virus type 1 (HIV1) tat and rev proteins. The SEAP or tk genes were placed between HIV1 splice donor and acceptor sites. One SEAP construct carried a series of alternating splice donor and a cceptor sites. In all cases, the rev response element mapped within an intron. Despite such mimicry of the HIV1 genome, residual expression of the reporter gene in the absence of tat and rev was observed. These results, as well as non-specific T-cell recruitment, suggest limits t o the specificity of using HIV-activated toxic gene expression to kill HIV-infected cells.