IL-29 is the dominant type III interferon produced by hepatocytes during acute hepatitis C virus infection
Open Access
- 18 June 2012
- journal article
- viral hepatitis
- Published by Ovid Technologies (Wolters Kluwer Health) in Hepatology
- Vol. 56 (6), 2060-2070
- https://doi.org/10.1002/hep.25897
Abstract
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)This publication has 32 references indexed in Scilit:
- Hepatitis C virus induces interferon-λ and interferon-stimulated genes in primary liver culturesHepatology, 2011
- Interferons α and λ Inhibit Hepatitis C Virus Replication With Distinct Signal Transduction and Gene Regulation KineticsGastroenterology, 2006
- Silencing of USP18 Potentiates the Antiviral Activity of Interferon Against Hepatitis C Virus InfectionGastroenterology, 2006
- Lambda Interferon (IFN-λ), a Type III IFN, Is Induced by Viruses and IFNs and Displays Potent Antiviral Activity against Select Virus Infections In VivoJournal of Virology, 2006
- A T-cell HCV vaccine eliciting effective immunity against heterologous virus challenge in chimpanzeesNature Medicine, 2006
- Production of infectious hepatitis C virus in tissue culture from a cloned viral genomeNature Medicine, 2005
- Lambda Interferon Inhibits Hepatitis B and C Virus ReplicationJournal of Virology, 2005
- IFN-α Regulates TLR-Dependent Gene Expression of IFN-α, IFN-β, IL-28, and IL-29The Journal of Immunology, 2005
- IFN-λs mediate antiviral protection through a distinct class II cytokine receptor complexNature Immunology, 2002
- DNA Microarray Analysis of Chimpanzee Liver during Acute Resolving Hepatitis C Virus InfectionJournal of Virology, 2001