Chicken ovalbumin upstream promoter transcription factor, a transcriptional activator of HIV-1 gene expression in human brain cells.
Viral infection of the central nervous system by the human immunodeficiency virus type 1 leads to a wide range of neuropathological disorders. However, the molecular mechanisms governing transcription of the human immunodeficiency virus type 1 genome in brain remain unclear. We have recently established that in brain cells, proteins belonging to the steroid/thyroid/retinoic acid receptor family bind to the -352 to -320 region of the long terminal repeat (LTR). Here, by supershift experiments, we have identified chicken ovalbumin upstream promoter transcription factor (COUP-TF), an orphan member of this nuclear receptor family, as one of the major proteins interacting with this LTR site. Cotransfection studies revealed that COUP-TF is able to dramatically activate LTR-directed gene transcription in human oligodendroglioma but not in astrocytoma cells. This activation occurs through two mechanisms, depending on the LTR sequence. Moreover, in neuronal cells COUP-TF and dopamine, a catecholamine neurotransmitter, enhance LTR-directed transcription by acting on the proximal LTR region. These results reveal the importance of COUP-TF and the dopamine signaling pathway as activators of human immunodeficiency virus type 1 gene expression in brain.
Sawaya
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Unité 338 INSERM, 5, rue Blaise Pascal, 67084 Strasbourg, France.
Rohr
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Aunis
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Schaeffer
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D001921:Brain / Q000166:cytology / Q000821:virology*; D001932:Brain Neoplasms; D051838:COUP Transcription Factor I; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000821:virology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000821:virology; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D051838:COUP Transcription Factor I; D004268:DNA-Binding Proteins; C497589:NR2F1 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D004298:Dopamine