Tumor necrosis factor α activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF-κB sites in the long terminal repeat

Abstract

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-κB sites in the LTR. Deletion of the NF-κB 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-κB sequences in the HIV LTR.