Article first published online: 19 NOV 2012
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 56, Issue 6, pages 2060–2070, December 2012
How to Cite
Park, H., Serti, E., Eke, O., Muchmore, B., Prokunina-Olsson, L., Capone, S., Folgori, A. and Rehermann, B. (2012), IL-29 is the dominant type III interferon produced by hepatocytes during acute hepatitis C virus infection. Hepatology, 56: 2060–2070. doi: 10.1002/hep.25897
Potential conflict of interest: Nothing to report.
This study was supported by the intramural research programs of the National Institute of Diabetes and Digestive and Kidney Diseases and National Cancer Institute of the National Institutes of Health. The authors thank Volker Lohmann for the Huh7-HCV-Luc cells.
- Issue published online: 4 DEC 2012
- Article first published online: 19 NOV 2012
- Accepted manuscript online: 18 JUN 2012 04:59AM EST
- Manuscript Accepted: 30 MAY 2012
- Manuscript Received: 20 JAN 2012
Early, vigorous intrahepatic induction of interferon (IFN)-stimulated gene (ISG) induction is a feature of hepatitis C virus (HCV) infection, even though HCV inhibits the induction of type I IFNs in vitro. To identify the cytokines and cells that drive ISG induction and mediate antiviral activity during acute HCV infection, type I and III IFN responses were studied in (1) serial liver biopsies and plasma samples obtained from 6 chimpanzees throughout acute HCV infection and (2) primary human hepatocyte (PHH) cultures upon HCV infection. Type I IFNs were minimally induced at the messenger RNA (mRNA) level in the liver and were undetectable at the protein level in plasma during acute HCV infection of chimpanzees. In contrast, type III IFNs, in particular, interleukin (IL)-29 mRNA and protein, were strongly induced and these levels correlated with ISG expression and viremia. However, there was no association between intrahepatic or peripheral type III IFN levels and the outcome of acute HCV infection. Infection of PHH with HCV recapitulated strong type III and weak type I IFN responses. Supernatants from HCV-infected PHH cultures mediated antiviral activity upon transfer to HCV-replicon–containing cells. This effect was significantly reduced by neutralization of type III IFNs and less by neutralization of type I IFNs. Furthermore, IL-29 production by HCV-infected PHH occurred independently from type I IFN signaling and was not enhanced by the presence of plasmacytoid dendritic cells. Conclusion: Hepatocyte-derived type III IFNs contribute to ISG induction and antiviral activity, but are not the principal determinant of the outcome of HCV infection. (HEPATOLOGY 2012;56:2060–2070)