trans-Activation 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 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.
Baier-Bitterlich
G
G
Institute for Medical Chemistry and Biochemistry, University of Innsbruck, Austria.
Fuchs
D
D
Zangerle
R
R
Baeuerle
P A
PA
Werner
E R
ER
Fresser
F
F
Uberall
F
F
Baier
G
G
Wachter
H
H
D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D016655:HIV Core Protein p24 / Q000097:blood; D006679:HIV Seropositivity / Q000097:blood / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D016328:NF-kappa B / Q000378:metabolism; D019798:Neopterin / Q000031:analogs & derivatives; D011401:Promoter Regions, Genetic; D011621:Pteridines / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016655:HIV Core Protein p24; D016328:NF-kappa B; D011621:Pteridines; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C000976:7,8-dihydroneopterin; D001708:Biopterins; D019798:Neopterin; D015500:Chloramphenicol O-Acetyltransferase