Effects of enhancer mutations on the expression of human immunodeficiency virus 1-regulated luciferase and diphtheria toxin A chain genes in transfected cells.

This study explores human immunodeficiency virus 1 (HIV-1)-regulated diphtheria toxin A (DT-A) gene expression as a means of eradicating HIV-infected cells. Previously, we constructed luciferase and DT-A plasmids, containing cis-acting Tat and Rev responsive elements, which showed low basal expression and required both Tat and Rev for maximal expression. Cell lines which had stably integrated the DT-A constructs were resistant to HIV production. To reduce toxicity due to basal expression, this study investigates the effect of mutations in the HIV enhancer on expression of luciferase and DT-A plasmids. Some mutations were found to substantially reduce basal expression while still allowing for trans-activation. Such mutations, in combination with attenuated versions of DT-A, may make regulated toxin gene expression feasible as a therapy for AIDS.