Modulation of HIV-1 enhancer activity and virus production by cAMP.
The effect of cAMP on the transcriptional activity of the HIV-1 long terminal repeat/enhancer was investigated and compared to the effect of cAMP on virus replication. In culture cAMP repressed virus replication in vivo using different cell types. Transient transfection studies with HIV-1 enhancer-derived luciferase reporter gene constructs identified the minimal DNA sequence mediating the negative regulatory effect of cAMP on HIV-1 transcription. A single nuclear factor kappaB element from the HIV-1 enhancer mediates the repressive effect on transcription. AP-2 is not involved in cAMP repression. Stable transfection of Jurkat T cells with the co-activators CREB binding protein (CBP) and p300 completely abolished the cAMP repressive effect, supporting the hypothesis that elevation of intracellular cAMP increases phosphorylation of CREB, which then competes with phosphorylated p65 and Ets-1 for limiting amounts of CBP/p300 thereby mediating the observed repressive effect on transcription. These findings suggest an important role of cAMP on HIV-1 transcription.
Banas
B
B
Medizinische Poliklinik, Ludwig-Maximilians-Universität München, Molekulare Infektiologie, Pettenkoferstrasse 8a, D-80336 Munich, Germany. banas@medpoli.med.uni-muenchen.de
Eberle
J
J
Banas
B
B
Schlöndorff
D
D
Luckow
B
B
D001665:Binding Sites; D050882:CREB-Binding Protein; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D016322:HIV Enhancer / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D008214:Lymphocytes / Q000821:virology*; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D015534:Trans-Activators / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D015534:Trans-Activators; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D000242:Cyclic AMP; D050882:CREB-Binding Protein