Antiviral and Immunoregulatory Effects of Indoleamine-2,3-Dioxygenase in Hepatitis C Virus Infection.

Journal of Innate Immunity
Quentin LepillerHeidi Barth

Abstract

In patients with hepatitis C virus (HCV) infection, enhanced activity of indoleamine-2,3-dioxygenase 1 (IDO) has been reported. IDO - a tryptophan-catabolizing enzyme - has been considered as both an innate defence mechanism and an important regulator of the immune response. The molecular mechanism of IDO induction in HCV infection and its role in the antiviral immune response remain unknown. Using primary human hepatocytes, we show that HCV infection stimulates IDO expression. IDO gene induction was transient and coincided with the expression of types I and III interferons (IFNs) and IFN-stimulated genes in HCV-infected hepatocytes. Overexpression of hepatic IDO prior to HCV infection markedly impaired HCV replication in hepatocytes, suggesting that IDO limits the spread of HCV within the liver. siRNA-mediated IDO knock-down revealed that IDO functions as an IFN-mediated anti-HCV effector. Hepatic IDO was most potently induced by IFN-x03B3;, and ongoing HCV replication could significantly upregulate IDO expression. IRF1 (IFN-regulatory factor 1) and STAT1 (signal transducer and activator of transcription 1) regulated hepatic IDO expression. Hepatic IDO expression also had a significant inhibitory effect on CD4+ T-cell prolifer...Continue Reading

Citations

Oct 13, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sachiyo YoshioTatsuya Kanto
Nov 13, 2015·Current Opinion in Clinical Nutrition and Metabolic Care·Barbara StrasserDietmar Fuchs
Aug 27, 2015·International Journal of Tryptophan Research : IJTR·Vikram Mehraj, Jean-Pierre Routy
Apr 22, 2017·World Journal of Gastroenterology : WJG·Kashif AsgharMuhammad Usman Rashid
Dec 21, 2020·European Journal of Medicinal Chemistry·Rahul Singh, Deepak B Salunke

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