Tumor necrosis factor α induces expression of human immunodeficiency virus in a chronically infected T-cell clone

Tumor necrosis factor α (TNF-α), also known as cachectin, was demonstrated to induce the expression of human immunodeficiency virus (HIV) in a chronically infected T-cell clone (ACH-2). Concentrations of recombinant TNF-α as low as 50 pg/ml induced a significant increase over background of HIV expression in the ACH-2 cells as determined by supernatant reverse transcriptase activity. The HIV-inducing effects of TNF-α could not be explained by toxic effects on the cells. In addition, both the uninfected parental cell line (A3.01) and the infected ACH-2 cells were shown to have high-affinity receptors for TNF-α. Transient-transfection experiments demonstrated that the inductive effects of TNF-α were due to specific activation of the HIV long terminal repeat. These studies provide evidence that TNF-α may play a role in the mechanisms of pathogenesis of HIV infection.