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.
Harrison
G S
GS
Division of Medical Oncology, University of Colorado Health Sciences Center, Denver 80262.
Long
C J
CJ
Castillo
I
I
D004167:Diphtheria Toxin / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics*; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics*; D010957:Plasmids; D014162:Transfection
D004167:Diphtheria Toxin; D010446:Peptide Fragments; C029795:diphtheria toxin fragment A; D008156:Luciferases