trans-Activation of the HIV type 1 promoter by 7,8-dihydroneopterin in vitro

AIDS Res Hum Retroviruses. 1997 Jan 20;13(2):173-8. doi: 10.1089/aid.1997.13.173.

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 gamma. 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-kappaB are activated by 7,8-dihydroneopterin, either directly (AP-1), or by the synergistic action with tumor necrosis factor alpha (NF-kappaB). 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biopterin / analogs & derivatives
  • Biopterin / blood
  • Chloramphenicol O-Acetyltransferase / genetics
  • Gene Expression Regulation, Viral / drug effects*
  • HIV Core Protein p24 / blood
  • HIV Seropositivity / blood
  • HIV Seropositivity / virology
  • HIV-1 / genetics*
  • Humans
  • Jurkat Cells
  • NF-kappa B / metabolism
  • Neopterin
  • Promoter Regions, Genetic*
  • Pteridines / pharmacology*
  • Recombinant Fusion Proteins / genetics
  • Transcription Factor AP-1 / metabolism
  • Transcriptional Activation*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • HIV Core Protein p24
  • NF-kappa B
  • Pteridines
  • Recombinant Fusion Proteins
  • Transcription Factor AP-1
  • Tumor Necrosis Factor-alpha
  • 7,8-dihydroneopterin
  • Biopterin
  • Neopterin
  • Chloramphenicol O-Acetyltransferase