Stimulation of HIV type 1 gene expression and induction of NF-kappa B (p50/p65)-binding activity in tumor necrosis factor alpha-treated human fetal glial cells.
In vitro, HIV-1 infection of human fetal glial cells initiates a noncytopathic, productive infection that results in a long-term persistence during which the viral genome remains latent. The cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) reactivate HIV-1 gene expression in these cells, leading to production of infectious virus. Here we show that treatment of human fetal glial cells with TNF-alpha and IL-1 beta increase expression of the reporter gene chloramphenicol acetyltransferase (CAT) when placed under the control of the HIV-1 5' LTR. We also show that treatment of human fetal glial cells with TNF-alpha leads to increased binding of the nuclear transcription factor NF-kappa B (p50/p65) to a consensus kappa B-binding site present in the HIV-1 5'LTR. Our results suggest that TNF-alpha stimulation of HIV-1 gene expression in primary cultures of human fetal glial cells is mediated by an increase in binding of NF-kappa B (p50/p65) to the HIV-1 LTR. This is the first report documenting NF-kappa B-binding activity in primary cultures of human fetal glial cells.
Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892.
W J
WJ
Atwood
C S
CS
Tornatore
R
R
Traub
K
K
Conant
P D
PD
Drew
E O
EO
Major
D001483:Base Sequence; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D005333:Fetus; D015870:Gene Expression / Q000187:drug effects*; D016679:Genome, Viral; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000096:biosynthesis* / Q000378:metabolism; D052002:NF-kappa B p50 Subunit; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D015345:Oligonucleotide Probes; D051996:Transcription Factor RelA; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D017735:Virus Latency
D016207:Cytokines; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D015345:Oligonucleotide Probes; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha