Hexamethylene bisacetamide activates the human immunodeficiency virus type 1 provirus by an NF-kappa B-independent mechanism.
Expression of the human immunodeficiency virus type 1 (HIV-1) provirus in T lymphocytic and monocytic cells can be induced by treatment with hexamethylene bisacetamide (HMBA). The induction occurs at the transcriptional level within 1 to 3 h after the addition of the drug, and is not associated with detectable changes in the binding of transcription factors to the enhancer, TATA box or other regulatory regions of the HIV-1 long terminal repeat (LTR). Using the 5' deletion mutants of HIV-1 LTR controlling the expression of the chloramphenicol acetyltransferase gene, we found that the deletion of the kappa B enhancer did not affect HIV-1 inducibility, whereas the deletion of the Sp1 binding sites abolished transcriptional activation. However, the presence of the HIV-1 LTR Sp1 binding sites in the context of the heterologous promoter did not induce responsiveness to HMBA. We conclude that HMBA increases transcription through the secondary modification of the basal transcription complex suggesting the existence of a regulatory pathway that circumvents the requirement for the induction of NF-kappa B or other DNA-specific binding proteins.
Vlach
J
J
Oncology Center, Johns Hopkins University, Baltimore, Maryland 21231.
Pitha
P M
PM
D000081:Acetamides / Q000494:pharmacology*; D002460:Cell Line; D005814:Genes, Viral / Q000187:drug effects; D016322:HIV Enhancer / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D006801:Humans; D009000:Monocytes; D016328:NF-kappa B / Q000187:drug effects*; D011401:Promoter Regions, Genetic / Q000502:physiology; D011533:Proviruses / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D013601:T-Lymphocytes; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D014775:Virus Activation / Q000187:drug effects*
D000081:Acetamides; D016328:NF-kappa B; C014026:hexamethylene bisacetamide