trans-Activation of the HIV Type 1 Promoter by 7,8-Dihydroneopterinin Vitro

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Abstract
Infection with human immunodeficiency virus type 1 and 2 is associated with elevated concentrations of neopterin, released in large quantities by human macrophages on stimulation with interferon γ. Evidence has suggested a potential role of neopterin derivatives in oxygen radical-mediated processes. Here we show that the redox-sensitive transcription factors AP-1 and NF-κB are activated by 7,8-dihydroneopterin, either directly (AP-1), or by the synergistic action with tumor necrosis factor α (NF-κB). We could further demonstrate that 7,8-dihydroneopterin enhances HIV-1 expression as shown in transient transfection assays using HIV-1 CAT promoter-reporter gene constructs. In sera of HIV+ patients 7,8-dihydroneopterin significantly correlated with neopterin and HIV-1 p24 antigen. On the basis of our data we therefore assume that 7,8-dihydroneopterin might augment progression to higher stages of HIV-associated disease.