1. Inhibition of human herpes simplex virus type 2 by interferon gamma and tumor necrosis factor alpha is mediated by indoleamine 2,3-dioxygenase.
- Author
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Adams O, Besken K, Oberdörfer C, MacKenzie CR, Rüssing D, and Däubener W
- Subjects
- Cell Line, Tumor, Enzyme Activation, HeLa Cells, Herpesvirus 2, Human pathogenicity, Herpesvirus 2, Human physiology, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase, Recombinant Proteins, Tryptophan metabolism, Virus Replication drug effects, Antiviral Agents pharmacology, Herpesvirus 2, Human drug effects, Interferon-gamma pharmacology, Tryptophan Oxygenase biosynthesis, Tumor Necrosis Factor-alpha pharmacology
- Abstract
Genital herpes simplex virus type 2 (HSV-2) is a significant clinical problem. Infection in pregnancy may result in disseminated infection of the newborn with encephalitis. We analyzed the antiviral effects induced by interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) in cervix carcinoma cells (HeLa) and astrocytoma cells (86HG39). We found that replication of HSV-2 in HeLa cells and in 86HG39 cells is inhibited after stimulation of the cells by IFN-gamma and TNF-alpha. The antiviral effect of IFN-gamma is enhanced in the presence of TNF-alpha, while stimulation by TNF-alpha alone did not induce antiviral activity. We found that IFN-gamma induces a strong activation of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) and in addition, that the IFN-gamma-induced IDO activity was enhanced in the presence of TNF-alpha. Furthermore, we found that the induction of IDO activity is responsible for the inhibition of herpes simplex virus replication, since the presence of excess amounts of l-tryptophan abrogates the antiviral effect induced by IFN-gamma and the combination of IFN-gamma and TNF-alpha. We therefore conclude that the antiviral effect against HSV-2 mediated by type II interferon and TNF-alpha are dependent on IDO activation. more...
- Published
- 2004
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