Tumor Necrosis Factor α Activates Human Immunodeficiency Virus Type 1 through Induction of Nuclear Factor Binding to the NF-κ B Sites in the Long Terminal Repeat

Expression of human immunodeficiency virus type 1 (HIV-1) can be activated in a chronically infected T-cell line (ACH2 cells) by a cytokine, human tumor necrosis factor α (TNF-α ). TNF-α treatment of ACH2 cells resulted in an increase in steady-state levels of HIV RNA and HIV transcription. Gel mobility shift assays demonstrated that the transcriptional activation of the HIV long terminal repeat (LTR) by TNF-α was associated with the induction of a nuclear factor(s) binding to the NF-κ B sites in the LTR. Deletion of the NF-κ B sites from the LTR eliminated activation by TNF-α in T cells transfected with plasmids in which the HIV LTR directed the expression of the bacterial chloramphenicol acetyltransferase gene. Thus, TNF-α appears to activate HIV RNA and virus production by ACH2 cells through the induction of transcription-activating factors that bind to the NF-κ B sequences in the HIV LTR.