SALMONELLA-TYPHIMURIUM ACTIVATES HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN CHRONICALLY INFECTED PROMONOCYTIC CELLS BY INDUCING TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION

The effect of phagocytosis of Salmonella typhimurium on human immunode ficiency virus type 1 (HIV-1) production was investigated using a chro nically infected promonocytic cell line (U1) that contains HIV-1 provi rus but produces little or no HIV-1. The phagocytosis of virulent S. t yphimurium by U1 cells resulted in an increased HIV-1 expression as ev idenced by significant increase in HIV-1 p24 antigen in culture supern atants. In contrast, heat-killed S. typhimurium failed to induce HIV-1 expression. In addition, phagocytosis of virulent S. typhimurium and not of heat-killed S. typhimurium resulted in a significant induction of tumor necrosis factor-alpha (TNF-alpha) mRNA expression and secreti on of TNF-alpha by U1 cells. Furthermore, anti-TNF-alpha monoclonal an tibody inhibited S. typhimurium-induced HIV-1 p24 antigen production. These data suggest that S. typhimurium induces HIV-1 expression in U1 cells via production of TNF-alpha. (C) 1994 Academic Press, Inc.