This Article Full Text Full Text (PDF) Other Versions of this Article: JVI.02248-06v1 81/7/3662    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Larrea, E. Articles by Prieto, J. Search for Related Content PubMed PubMed Citation Articles by Larrea, E. Articles by Prieto, J.

 Previous Article  |  Next Article 

Journal of Virology, April 2007, p. 3662-3666, Vol. 81, No. 7
0022-538X/07/$08.00+0     doi:10.1128/JVI.02248-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Upregulation of Indoleamine 2,3-Dioxygenase in Hepatitis C Virus Infection

Esther Larrea,^1, José I. Riezu-Boj,^1, Lucía Gil-Guerrero,^1, Noelia Casares,¹ Rafael Aldabe,¹ Pablo Sarobe,¹ María P. Civeira,² Jonathan L. Heeney,³ Christine Rollier,³ Babs Verstrepen,³ Takaji Wakita,⁴ Francisco Borrás-Cuesta,¹ Juan J. Lasarte,^1,* and Jesús Prieto^1,2,*

Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra,¹ Liver Unit, University Clinic, University of Navarra, CIBERedh, Pamplona, Spain,² Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands,³ Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan⁴

Received 13 October 2006/ Accepted 3 January 2007

Indoleamine 2,3-dioxygenase (IDO) is induced by proinflammatory cytokines and by CTLA-4-expressing T cells and constitutes an important mediator of peripheral immune tolerance. In chronic hepatitis C, we found upregulation of IDO expression in the liver and an increased serum kynurenine/tryptophan ratio (a reflection of IDO activity). Huh7 cells supporting hepatitis C virus (HCV) replication expressed higher levels of IDO mRNA than noninfected cells when stimulated with gamma interferon or when cocultured with activated T cells. In infected chimpanzees, hepatic IDO expression decreased in animals that cured the infection, while it remained high in those that progressed to chronicity. For both patients and chimpanzees, hepatic expression of IDO and CTLA-4 correlated directly. Induction of IDO may dampen T-cell reactivity to viral antigens in chronic HCV infection.

Published ahead of print on 17 January 2007.

E.L., J.I.R.-B., and L.G.-G. contributed equally to this work.

J. J. Lasarte and J. Prieto are senior authors of this article.

This article has been cited by other articles:

• Dolganiuc, A., Szabo, G. (2008). T cells with regulatory activity in hepatitis C virus infection: what we know and what we don't. J. Leukoc. Biol. 84: 614-622 [Abstract] [Full Text]