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.
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Liu
authors.forename: Thu Le
authors.initials: TL
authors.lastname: Trinh
authors.forename: Huijia
authors.initials: H
authors.lastname: Dong
authors.forename: Robertson
authors.initials: R
authors.lastname: Keith
authors.forename: David
authors.initials: D
authors.lastname: Nelson
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
mesh_terms: D000107:Acetylation; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D019175:DNA Methylation; D016174:Hepacivirus / Q000472:pathogenicity*; D006526:Hepatitis C / Q000235:genetics / Q000378:metabolism*; D064451:Hepcidins; D006657:Histones / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D006657:Histones; D050796:STAT3 Transcription Factor; D012313:RNA; D007501:Iron