Hepatitis C virus induces interferon-λ and... : Hepatology (original) (raw)
Viral Hepatitis
Hepatitis C virus induces interferon-λ and interferon-stimulated genes in primary liver cultures
Marukian, Svetlana1; Andrus, Linda1; Sheahan, Timothy P.1; Jones, Christopher T.1; Charles, Edgar D.1; Ploss, Alexander1; Rice, Charles M.1; Dustin, Lynn B.1,*c
1_Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, Rockefeller University, New York, NY_
*Address reprint requests to: Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, Rockefeller University, Box 64, 1230 York Ave., New York, NY 10065
Email:[email protected]
Grant sponsor: The National Institutes of Health; Grant Numbers: R01 AI60561 K08 AI075031 R01 DK085713 R01 AI090055 F32 AI084448; Grant sponsor: The Irma T. Hirschl / Monique Weill-Caulier Trust; Grant sponsor: The Greenberg Institute for Medical Research.
Potential conflict of interest: Dr. Rice owns stock in Apath, LLC.
c_fax: 212-327-7048_
Abstract
Hepatitis C virus (HCV) replication in primary liver cells is less robust than that in hepatoma cell lines, suggesting that innate antiviral mechanisms in primary cells may limit HCV replication or spread. Here we analyzed the expression of 47 genes associated with interferon (IFN) induction and signaling following HCV infection of primary human fetal liver cell (HFLC) cultures from 18 different donors. We report that cell culture-produced HCV (HCVcc) induced expression of Type III (λ) IFNs and of IFN-stimulated genes (ISGs). Little expression of Type I IFNs was detected. Levels of IFNλ and ISG induction varied among donors and, often, between adapted and nonadapted HCV chimeric constructs. Higher levels of viral replication were associated with greater induction of ISGs and of λ IFNs. Gene induction was dependent on HCV replication, as ultraviolet light-inactivated virus was not stimulatory and an antiviral drug, 2′-C-methyladenosine, reduced induction of λ IFNs and ISGs. The level of IFNλ protein induced was sufficient to inhibit HCVcc infection of naïve cultures.
Conclusion:
Together, these results indicate that despite its reported abilities to blunt the induction of an IFN response, HCV infection is capable of inducing antiviral cytokines and pathways in primary liver cell cultures. Induction of ISGs and λ IFNs may limit the growth and spread of HCV in primary cell cultures and in the infected liver. HCV infection of HFLC may provide a useful model for the study of gene induction by HCV in vivo . (Hepatology 2011;)
Copyright © 2010 John Wiley & Sons, Inc.