Stimulation of HIV Type 1 Gene Expression and Induction of NF-κB (p50/p65)-Binding Activity in Tumor Necrosis Factor α-Treated Human Fetal Glial Cells

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Abstract
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 α (TNF-α) and interleukin 1β (IL-1β) 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-α and IL-1β 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-α leads to increased binding of the nuclear transcription factor NF-κB (p50/p65) to a consensus κB-binding site present in the HIV-1 5′ LTR. Our results suggest that TNF-α stimulation of HIV-1 gene expression in primary cultures of human fetal glial cells is mediated by an increase in binding of NF-κB (p50/p65) to the HIV-1 LTR. This is the first report documenting NF-κB-binding activity in primary cultures of human fetal glial cells.