title: 3-methylcholanthrene activates human immunodeficiency virus type 1 replication via aryl hydrocarbon receptor.
abstract: We found that 3-methylcholanthrene (3-MC) could induce the reactivation of human immunodeficiency virus type 1 (HIV-1) replication in OM 10.1 cell, promyelocytic cell line latently infected with HIV-1. Transient luciferase expression experiments have revealed no particular transcription factors that are responsible for the effect of 3-MC in inducing HIV-1 gene expression as HIV-1 LTR mutants lacking various upstream transcriptional activators similarly responded to 3-MC. In addition, there was no effect of 3-MC on the DNA binding activity of nuclear factor-kappa B (NF-kappaB) that was previously reported to be crucial for the effect of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), a chemical homologue of 3-MC. However, overexpression of wild type aryl hydrocarbon receptor (AhR), a nuclear receptor of polycyclic aromatic hydrocarbons (PAHs) such as 3-MC, augmented the effect of 3-MC in the induction of gene expression from HIV-1 LTR. Moreover, a dominant negative mutant of AhR dramatically reduced the 3-MC-mediated activation of HIV-1 LTR. These findings suggest that 3-MC stimulates HIV-1 transcription by interacting with general transcription factors. Our observations indicate that chronic exposure of the HIV-1 infected individuals to PAHs may be contributable to the clinical development of acquired immunodeficiency syndrome (AIDS) among the individuals infected with HIV.
authors.affiliation: Department of Molecular Genetics, Nagoya City University Medical School, Nagoya, Aichi 467-8601, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Ohata
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tetsuka
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Hayashi
authors.forename: Kikuo
authors.initials: K
authors.lastname: Onozaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Okamoto
mesh_terms: D002460:Cell Line; D002461:Cell Line, Transformed; D016325:HIV Long Terminal Repeat / Q000235:genetics / Q000502:physiology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008748:Methylcholanthrene / Q000494:pharmacology*; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014775:Virus Activation; D017735:Virus Latency; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D016328:NF-kappa B; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D008748:Methylcholanthrene