Prostaglandin E(2)-mediated activation of HIV-1 long terminal repeat transcription in human T cells necessitates CCAAT/enhancer binding protein (C/EBP) binding sites in addition to cooperative interactions between C/EBPbeta and cyclic adenosine 5'-monophosphate response element binding protein.
Previous work indicates that treatment of human T cells with PGE(2) results in an increase of HIV-1 long terminal repeat (LTR) transcriptional activity. The noticed PGE(2)-mediated activation of virus gene activity required the participation of specific intracellular second messengers such as calcium and two transcription factors, i.e., NF-kappaB and CREB. We report in this work that the nuclear transcription factor CCAAT/enhancer binding protein (C/EBP) is also important for PGE(2)-dependent up-regulation of HIV-1 LTR-driven gene activity. The implication of C/EBP was shown by using a trans-dominant negative inhibitor of C/EBP (i.e., liver-enriched transcriptional inhibitory protein) and several molecular constructs carrying site-directed mutations in the C/EBP binding sites located within the HIV-1 LTR. Mutated HIV-1 LTR constructs also revealed the involvement of the two most proximal C/EBP binding sites. Data from cotransfection experiments with vectors coding for dominant negative mutants and gel mobility shift assays indicated that PGE(2)-mediated induction of HIV-1 LTR activity results from a cooperative interaction between C/EBPbeta and CREB, two members of the basic leucine zipper family of transcription factors. Altogether these findings indicate that treatment of human T cells with PGE(2) induces HIV-1 LTR activity through a complex interplay between C/EBPbeta and CREB. Such a combinatorial regulation may represent a mechanism that permits a fine regulation of HIV-1 expression by PGE(2) in human T cells.
Dumais
Nancy
N
Centre de Recherche en Infectiologie, Hôpital CHUL, Centre Hospitalier Universitaire de Québec, Ste-Foy, Québec, Canada G1V 4G2.
Bounou
Salim
S
Olivier
Martin
M
Tremblay
Michel J
MJ
D021581:Active Transport, Cell Nucleus; D001665:Binding Sites; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism* / Q000502:physiology; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D019281:Dimerization; D015232:Dinoprostone / Q000494:pharmacology*; D024202:Electrophoretic Mobility Shift Assay; D015967:Gene Expression Regulation, Viral; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D020218:Response Elements; D013601:T-Lymphocytes / Q000378:metabolism*; D015533:Transcriptional Activation
D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D015232:Dinoprostone