Activation of the HIV-1 long terminal repeat by nerve growth factor.
The brain is an important target for the human immunodeficiency virus type 1 (HIV-1). We show here that nerve growth factor (NGF), which induces neuronal differentiation and survival, causes a strong activation of the HIV-1 long terminal repeat by a Ras/Raf-dependent mechanism in PC12 cells. Mutation of the kappaB sequences contained whithin the long terminal repeat reduces NGF-mediated stimulation. NGF does not activate NF-kappaB in PC12 cells, but rather increases binding of other nuclear factors to the kappaB sequences. Furthermore, a nuclear receptor response element contributes to the stimulatory effect of NGF. The retinoids receptors have been identified as components of the nuclear binding to the nuclear receptor response element in NGF-treated PC12 cells. These results reveal the importance of neurotrophins and nuclear receptor signaling pathways as specific activators of HIV-1 gene expression in neural cells.
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Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Arturo Duperier 4, 28029 Madrid, Spain.
Aranda
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D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D016325:HIV Long Terminal Repeat / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis; D016328:NF-kappa B / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014775:Virus Activation / Q000187:drug effects*
D016328:NF-kappa B; D009414:Nerve Growth Factors; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D008156:Luciferases