HUMAN FETAL GLIAL-CELLS CONSTITUTIVELY PRODUCE HIV-INDUCING CYTOKINES

The capacity of two human fetal glial cell lines, SVG and POJ, to incr ease the expression of human immunodeficiency virus (HIV) was investig ated. As a cellular model for HIV latency, a chronically infected prom onocytic cell line U1 was used. This cell line constitutively expresse s a low level of viral activity. To monitor the level of HIV expressio n in U1 cells, reverse transcriptase (RT) activity was measured in the supernatant and the level of total HIV proteins was determined in cel lular lysates. It was observed that the conditioned media from SVG and POJ cells increased RT activity in U1 cells in a dose-dependent fashi on. In addition, the conditioned media from fetal glial cells caused a n increase in total HIV protein synthesis. The capacity of conditioned media from both fetal glial cell lines to induce the expression of HI V was reduced by 45% in the presence of antibodies against human tumor necrosis factor alpha (TNF alpha), suggesting that one of the HIV-act ivating factors released by these cells was TNF alpha. The presence of TNF alpha and two other HIV-activating cytokines, IL-6 and IL-1, was confirmed by ELISA. It was also observed that glutathione increased th e HN-inducing capacity of the fetal glial cell-derived conditioned med ia. The finding that fetal glial cells constitutively secrete soluble factors which increase the expression of HN in vitro suggests that in vivo, during perinatally acquired infection, similar events may occur. Fetal glial cells may play an important role in the pathogenesis of H IV-related encephalopathy. (C) 1996 Academic Press, Inc.