SYNERGISTIC STIMULATORY EFFECTS OF TUMOR-NECROSIS-FACTOR-ALPHA AND INTERFERON-GAMMA 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 f or tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN- gamma) on replication of human immunodeficiency virus type 1 (HIV-1). The authors examined individual and coordinate action of these cytokin es on HIV-1 expression, and on apoptosis of HIV-1-infected host cells by determination of reverse transcriptase activity in cell culture sup ernatant, 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-alpha alone markedly stimulated HIV-1 replication in U1 cells at the transcriptional and on the translational level. Exclusive applica tion of IFN-gamma only slightly enhanced HIV-1 expression whereas it s ynergistically potentiated stimulatory effects of TNF-alpha. Both cyto kines also synergistically induced apoptosis in HIV-1-infected host ce lls. Co-ordinate action of TNF-alpha and IFN-gamma is suggested to rep resent 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.