Role of neopterin and 7,8-dihydroneopterin in human immunodeficiency virus infection: marker for disease progression and pathogenic link.

Abstract

Human immunodeficiency virus (HIV) infection is associated with increased concentrations of neopterin derivatives, released in large quantities by human macrophages on stimulation with interferon-gamma (INF-gamma). Neopterin concentrations thus inversely correlate with absolute CD4+ T-cell numbers and strongly predict progression of disease from latency to AIDS. Investigations of hydrogen peroxide-induced chemiluminescence indicated a potential role of neopterin and 7,8-dihydroneopterin in oxygen free radical-mediated processes. Indeed, 7,8-dihydroneopterin is able to enhance tumor necrosis factor alpha (TNF-alpha)-induced apoptosis, accompanied by an increased production of reactive oxygen intermediates (ROIs). In line with this finding, the same combination appears to contribute to the upregulation of HIV replication due to activation of nuclear factor-kappa B (NF-kappa B), a central enhancer element of the HIV LTR promoter. Thus, besides the role of neopterin as sensitive indicator of disease activity in HIV infection, neopterin derivatives apparently are associated with the cascade of events that regulate the HIV production in infected individuals.

• Authors: G Baier-Bitterlich, H Wachter, D Fuchs
• Journal: Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association (J Acquir Immune Defic Syndr Hum Retrovirol) Vol. 13 Issue 2 Pg. 184-93 (Oct 01 1996) ISSN: 1077-9450 [Print] United States
• PMID: 8862284 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Biomarkers
• Reactive Oxygen Species
• Tumor Necrosis Factor-alpha
• Biopterin
• Neopterin
• Interferon-gamma

Topics

• Apoptosis
• Biomarkers
• Biopterin (analogs & derivatives, metabolism, physiology)
• Disease Progression
• HIV Infections (immunology)
• HIV-1 (growth & development, pathogenicity)
• Humans
• Interferon-gamma (pharmacology)
• Lymphocytes (physiology)
• Macrophages (metabolism)
• Molecular Structure
• Neopterin
• Reactive Oxygen Species (metabolism)
• Risk Factors
• Tumor Necrosis Factor-alpha (pharmacology)