Synergistic stimulatory effects of tumour necrosis factor α and interferon γ on replication of human immunodeficiency virus type 1 and on apoptosis of HIV‐1‐infected host cells
Differential and sometimes contradictory effects have been described for tumour necrosis factor α (TNF‐α) and interferon γ (IFN‐γ) on replication of human immunodeficiency virus type 1 (HIV‐1). The authors examined individual and co‐ordinate action of these cytokines on HIV‐1 expression, and on apoptosis of HIV‐1‐infected host cells by determination of reverse transcriptase activity in cell culture supernatant, expression of HIV‐1‐RNA and production of p24 antigen in the promonocytic cell line U937 and its persistently HIV‐1‐infected clone U1. Apoptosis was demonstrated by typical cleavage of cellular DNA at internucleosomal regions in promonocytic and T‐lymphocytic cell lines. TNF‐α alone markedly stimulated HIV‐1 replication in U1 cells at the transcriptional and on the translational level. Exclusive application of IFN‐γ only slightly enhanced HIV‐1 expression, whereas it synergistically potentiated stimulatory effects of TNF‐α. Both cytokines also synergistically induced apoptosis in HIV‐1‐infected host cells. Co‐ordinate action of TNF‐α and IFN‐γ is suggested to represent an important mechanism for disease progression in HIV infection. These findings demonstrate that cytokine effects on viral expression may vary depending on their single or combined application.