Iron Regulator Hepcidin Exhibits Antiviral Activity against Hepatitis C Virus

Hongyan Liu, Thu Le Trinh, Huijia Dong, Keith D Robertson, David Nelson, Chen Liu

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Hepatitis C viral infection affects 170 million people worldwide. It causes serious chronic liver diseases. HCV infection has been implicated in iron accumulation in the liver and iron overload has been shown to be a potential cofactor for HCV associated hepatocellular carcinoma progression. The underlying mechanisms are not understood. Human hepcidin, a 25 amino acid peptide mainly produced by hepatocytes, is a key regulator of iron metabolism. Alteration of hepcidin expression levels has been reported in the setting of chronic HCV infection and hepatocellular carcinoma. In this study, we aim to examine the interactions between HCV infection and hepcidin expression in liver cells. We found that hepcidin expression was suppressed in HCV infected cells. The suppressive effect appears to be regulated by histone acetylation but not DNA methylation. Moreover, we found that hepcidin had a direct antiviral activity against HCV replication in cell culture. The antiviral effect is associated with STAT3 activation. In conclusion, hepcidin can induce intracellular antiviral state while HCV has a strategy to suppress hepcidin expression. This may be a novel mechanism by which HCV circumvents hepatic innate antiviral defense.

Original languageEnglish (US)
Article numbere46631
JournalPLoS One
Volume7
Issue number10
DOIs
StatePublished - Oct 22 2012
Externally publishedYes

Fingerprint

Hepcidins
Hepatitis C virus
Viruses
Hepacivirus
Antiviral Agents
Iron
iron
Liver
hepatoma
Hepatocellular Carcinoma
infection
hepatocytes
Infection
Iron Overload
iron overload
hepatitis C
Acetylation
Virus Diseases
DNA Methylation
liver

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Iron Regulator Hepcidin Exhibits Antiviral Activity against Hepatitis C Virus. / Liu, Hongyan; Trinh, Thu Le; Dong, Huijia; Robertson, Keith D; Nelson, David; Liu, Chen.

In: PLoS One, Vol. 7, No. 10, e46631, 22.10.2012.

Research output: Contribution to journalArticle

Liu, Hongyan ; Trinh, Thu Le ; Dong, Huijia ; Robertson, Keith D ; Nelson, David ; Liu, Chen. / Iron Regulator Hepcidin Exhibits Antiviral Activity against Hepatitis C Virus. In: PLoS One. 2012 ; Vol. 7, No. 10.
@article{3dbb9798ebf344b6bad7f9f41d2cd7e3,
title = "Iron Regulator Hepcidin Exhibits Antiviral Activity against Hepatitis C Virus",
abstract = "Hepatitis C viral infection affects 170 million people worldwide. It causes serious chronic liver diseases. HCV infection has been implicated in iron accumulation in the liver and iron overload has been shown to be a potential cofactor for HCV associated hepatocellular carcinoma progression. The underlying mechanisms are not understood. Human hepcidin, a 25 amino acid peptide mainly produced by hepatocytes, is a key regulator of iron metabolism. Alteration of hepcidin expression levels has been reported in the setting of chronic HCV infection and hepatocellular carcinoma. In this study, we aim to examine the interactions between HCV infection and hepcidin expression in liver cells. We found that hepcidin expression was suppressed in HCV infected cells. The suppressive effect appears to be regulated by histone acetylation but not DNA methylation. Moreover, we found that hepcidin had a direct antiviral activity against HCV replication in cell culture. The antiviral effect is associated with STAT3 activation. In conclusion, hepcidin can induce intracellular antiviral state while HCV has a strategy to suppress hepcidin expression. This may be a novel mechanism by which HCV circumvents hepatic innate antiviral defense.",
author = "Hongyan Liu and Trinh, {Thu Le} and Huijia Dong and Robertson, {Keith D} and David Nelson and Chen Liu",
year = "2012",
month = "10",
day = "22",
doi = "10.1371/journal.pone.0046631",
language = "English (US)",
volume = "7",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "10",

}

TY - JOUR

T1 - Iron Regulator Hepcidin Exhibits Antiviral Activity against Hepatitis C Virus

AU - Liu, Hongyan

AU - Trinh, Thu Le

AU - Dong, Huijia

AU - Robertson, Keith D

AU - Nelson, David

AU - Liu, Chen

PY - 2012/10/22

Y1 - 2012/10/22

N2 - Hepatitis C viral infection affects 170 million people worldwide. It causes serious chronic liver diseases. HCV infection has been implicated in iron accumulation in the liver and iron overload has been shown to be a potential cofactor for HCV associated hepatocellular carcinoma progression. The underlying mechanisms are not understood. Human hepcidin, a 25 amino acid peptide mainly produced by hepatocytes, is a key regulator of iron metabolism. Alteration of hepcidin expression levels has been reported in the setting of chronic HCV infection and hepatocellular carcinoma. In this study, we aim to examine the interactions between HCV infection and hepcidin expression in liver cells. We found that hepcidin expression was suppressed in HCV infected cells. The suppressive effect appears to be regulated by histone acetylation but not DNA methylation. Moreover, we found that hepcidin had a direct antiviral activity against HCV replication in cell culture. The antiviral effect is associated with STAT3 activation. In conclusion, hepcidin can induce intracellular antiviral state while HCV has a strategy to suppress hepcidin expression. This may be a novel mechanism by which HCV circumvents hepatic innate antiviral defense.

AB - Hepatitis C viral infection affects 170 million people worldwide. It causes serious chronic liver diseases. HCV infection has been implicated in iron accumulation in the liver and iron overload has been shown to be a potential cofactor for HCV associated hepatocellular carcinoma progression. The underlying mechanisms are not understood. Human hepcidin, a 25 amino acid peptide mainly produced by hepatocytes, is a key regulator of iron metabolism. Alteration of hepcidin expression levels has been reported in the setting of chronic HCV infection and hepatocellular carcinoma. In this study, we aim to examine the interactions between HCV infection and hepcidin expression in liver cells. We found that hepcidin expression was suppressed in HCV infected cells. The suppressive effect appears to be regulated by histone acetylation but not DNA methylation. Moreover, we found that hepcidin had a direct antiviral activity against HCV replication in cell culture. The antiviral effect is associated with STAT3 activation. In conclusion, hepcidin can induce intracellular antiviral state while HCV has a strategy to suppress hepcidin expression. This may be a novel mechanism by which HCV circumvents hepatic innate antiviral defense.

UR - http://www.scopus.com/inward/record.url?scp=84867692347&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867692347&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0046631

DO - 10.1371/journal.pone.0046631

M3 - Article

C2 - 23110054

AN - SCOPUS:84867692347

VL - 7

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 10

M1 - e46631

ER -