Hepatology
Early View (Articles online in advance of print)
Published Online: 17 Aug 2005

Viral Hepatitis
Analysis of ISG expression in chronic hepatitis C identifies viperin as a
potential antiviral effector
Karla J. Helbig 1 2, Daryl T.-Y. Lau 3, Ljiljana Semendric 1 2, Hugh A. J.
Harley 4, Michael R. Beard 1 2 *
1Infectious Diseases Laboratories and Hanson Institute, Institute of Medical
and Veterinary Science, Adelaide, South Australia
2School of Molecular and Biomedical Science, University of Adelaide,
Adelaide, South Australia
3Division of Gastroenterology and Hepatology, Department of Internal
Medicine, The University of Texas Medical Branch, Galveston, TX
4Department of Gastroenterology, Royal Adelaide Hospital, Adelaide, South
Australia

email: Michael R. Beard (michael.beard@...)

*Correspondence to Michael R. Beard, School of Molecular and Biomedical
Science, The University of Adelaide, North Terrace, Adeleide, South
Australia, 5005, Australia

Potential conflict of interest: Nothing to report.
fax: (61) 08-8303-7532

Funded by:
NH&MRC of Australia
Royal Adelaide Hospital Florey Fellowship Fund

Abstract
Interferon (IFN) inhibits hepatitis C virus (HCV) replication both
clinically and in vitro; however, the complete spectrum of
interferon-stimulated genes (ISGs) expressed in the HCV-infected liver or
the genes responsible for control of HCV replication have not been defined.
To better define ISG expression in the chronically infected HCV liver, DNA
microarray analysis was performed on 9 individuals with chronic hepatitis C
(CHC). A total of 232 messenger RNAs were differentially regulated in CHC
compared with nondiseased liver controls. A significant proportion of these
were potential ISGs that were transcriptionally elevated, suggesting an
ongoing response to endogenous IFN and/or double-stranded RNA. One ISG
significantly elevated in all patients was viperin, an evolutionary
conserved ISG that has antiviral activity against human cytomegalovirus.
Stimulation of Huh-7 and HepG2 cells with IFN- or - revealed viperin is
predominantly a type I ISG. Furthermore, viperin expression could also be
induced following transfection of Huh-7 cells with either poly(I:C) or HCV
RNA. Transient expression of viperin in cells harboring the HCV genomic
replicon resulted in a significant decrease in HCV replication, suggesting
that viperin has anti-HCV activity. In conclusion, even in the face of a
persistent HCV infection, there is an active ISG antiviral cellular
response, highlighting the complexity of the host viral relationship.
Furthermore, ISG viperin has anti-HCV activity in vitro; we postulate that
viperin, along with other ISGs, acts to limit HCV replication. (HEPATOLOGY
2005.)



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Received: 3 April 2005; Accepted: 21 June 2005
Digital Object Identifier (DOI)

10.1002/hep.20844 About DOI




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