ROLE OF 7,8-DIHYDRONEOPTERIN IN T-CELL APOPTOSIS AND HTLV-1 TRANSCRIPTION IN-VITRO

Adult T-cell leukemia is associated with high levels of neopterin, rel eased in large amounts from human macrophages upon stimulation with in terferon-gamma. Recent data suggested a potential role of neopterin-de rivatives in oxygen radical-mediated processes, and evidence accumulat es that oxidative stress is involved in the pathogenesis of viral dise ases. We now report that increased concentrations of 7,8-dihydroneopte rin may lead to enhanced apoptosis and disturbance of the redox-balanc e of human leukemic Jurkat T cells. Additionally, we demonstrate that 7,8-dihydroneopterin and hydrogen peroxide activate the type 1 human T -cell leukemia virus (HTLV-1) long terminal repeat (LTR). Furthermore, we found that the activity of the HTLV-1 transactivator protein Tax i s amplified by an elevated concentration of 7,8-dihydroneopterin. Tax did not significantly augment 7,8-dihydroneopterin mediated apoptosis. Based on our data we propose that 7,8-dihydroneopterin may be involve d in the progression to higher stages of HTLV-1 associated disease.