3‐Methylcholanthrene Activates Human Immunodeficiency Virus Type 1 Replication via Aryl Hydrocarbon Receptor
3‐Methylcholanthrene Activates Human Immunodeficiency Virus Type 1 Replication via Aryl Hydrocarbon Receptor
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DOI：
10.1111/j.1348-0421.2003.tb03408.x
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发表时间：
2003-05
影响因子：
2.6
通讯作者：
H. Ohata;T. Tetsuka;H. Hayashi;K. Onozaki;T. Okamoto
中科院分区：
文献类型：
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作者：
H. Ohata;T. Tetsuka;H. Hayashi;K. Onozaki;T. Okamoto
我们发现3-甲基胆蒽（3-MC）可以诱导潜伏感染HIV-1的早幼粒细胞系OM 10.1细胞重新激活HIV-1复制。瞬时荧光素酶表达实验显示，没有特定的转录因子负责3-MC诱导HIV-1基因表达的作用，因为缺乏各种上游转录激活因子的HIV-1 LTR突变体对3-MC有类似的反应。此外，3-MC对核因子-κ B（NF-κB）的DNA结合活性没有影响，而之前报道的NF-κ B对3-MC的化学同系物2，3，7，8-四氯二苯并-对-二恶英（TCDD）的作用至关重要。然而，野生型芳烃受体（AhR），多环芳烃（PAH）如3-MC的核受体的过表达，增强了3-MC在诱导HIV-1 LTR基因表达中的作用。此外，AhR的显性阴性突变体显著降低了3-MC-介导的HIV-1 LTR活化。这些发现表明，3-MC通过与一般转录因子相互作用刺激HIV-1转录。我们的观察结果表明，HIV-1感染者长期暴露于多环芳烃可能有助于HIV感染者获得性免疫缺陷综合征（AIDS）的临床发展。
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‐κB) 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.