TRANSACTIVATION OF THE HIV TYPE-1 PROMOTER BY 7,8-DIHYDRONEOPTERIN IN-VITRO

Infection with human immunodeficiency virus type 1 and 2 is associated with elevated concentrations of neopterin, released in large quantiti es by human macrophages on stimulation with interferon gamma. Evidence has suggested a potential role of neopterin derivatives in oxygen rad ical-mediated processes. Here we show that the redox-sensitive transcr iption factors AP-1 and NF-kappa B are activated by 7,8-dihydroneopter in, either directly (AP-1), or by the synergistic action with tumor ne crosis factor alpha (NF-kappa B). We could further demonstrate that 7, 8-dihydroneopterin enhances HIV-1 expression as shown in transient tra nsfection assays using HIV-1 CAT promoter-reporter gene constructs, In sera of HIV+ patients 7,8-dihydroneopterin significantly correlated w ith neopterin and HIV-1 p24 antigen, On the basis of our data we there fore assume that 7,8-dihydroneopterin might augment progression to hig her stages of HIV-associated disease.