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 immunodefic iency virus type 1 leads to a wide range of neuropathological disorder s. However, the molecular mechanisms governing transcription of the hu man immunodeficiency virus type 1 genome in brain remain unclear.We ha ve recently established that in brain cells, proteins belonging to the steroid/thyroid/ retinoic acid receptor family bind to the -352 to -3 20 region of the long terminal repeat (LTR). Here, by supershift exper iments, we have identified chicken ovalbumin upstream promoter transcr iption factor (COUP-TF), an orphan member of this nuclear receptor fam ily, as one of the major proteins interacting with this LTR site. Cotr ansfection studies revealed that COUP-TF is able to dramatically activ ate 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 tran scription by acting on the proximal LTR region. These results reveal t he importance of COUP-TF and the dopamine signaling pathway as activat ors of human immunodeficiency virus type 1 gene expression in brain.