Regulation of human immunodeficiency virus type 1 gene transcription by nuclear receptors in human brain cells.
Infection of cells of the central nervous system by the human immunodeficiency virus type-1 (HIV-1) leads to HIV-1-associated neuropathology. Recent studies have demonstrated the importance of long terminal repeat (LTR) binding sites in determining the pathogenicity of HIV. Here we have investigated the presence and the functional role of transcription factors that have the potential to interact, directly or indirectly, with the nuclear receptor-responsive element in the LTR of HIV-1, in different human cell lines of the brain. Cotransfection experiments showed that in oligodendroglioma TC-620 cells, the retinoic acid receptor and the retinoid X receptor activate LTR-driven transcription in the absence of ligand. Addition of all-trans- or 9-cis-retinoic acid reverses this effect. In contrast, in astrocytoma, neuronal, and microglial cells, no significant effect of the retinoid acid pathway was detected. This retinoid response is mediated by distinct molecular interactions in the lymphotropic LAI and the neurotropic JR-CSF HIV-1 strains. Moreover, retinoid receptors were found to antagonize the chicken ovalbumin upstream promoter transcription factor- as well as the c-JUN-mediated LTR transactivation. Our findings demonstrate the importance of the retinoic acid signaling pathway and of cross-coupling interactions in the repression of HIV-1 LTR gene expression.
Sawaya
B E
BE
Unité 338 INSERM, 5, rue Blaise Pascal, 67084 Strasbourg Cedex, France.
Rohr
O
O
Aunis
D
D
Schaeffer
E
E
D001921:Brain / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D017353:Gene Deletion; D015967:Gene Expression Regulation, Viral; D017930:Genes, Reporter; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D047488:Retinoid X Receptors; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology
D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin