title: Zinc is a negative regulator of hepatitis C virus RNA replication.
abstract: OBJECTIVE
  Hepatitis C virus (HCV) infection is a significant global public health problem. In clinical studies, zinc has been closely related to the pathogenesis of chronic hepatitis C. However, the role of zinc in both viral replication and the expression of viral proteins remains unclear. We aimed to clarify the effect of zinc on the replication of HCV in vitro.
  
  
  METHODS
  We incubated subgenomic HCV replicon cells (sO) and genome-length HCV RNA-replicating cells (O) treated with several chemicals including trace elements. Total RNAs were collected and subjected to real-time reverse-transcriptase polymerase chain reaction in order to examine the level of HCV RNA replication, and Western blotting was performed to confirm the expression of viral proteins.
  
  
  RESULTS
  Iron salts and interferon-alpha suppressed HCV RNA replication and protein expression in both sO and O cells. Zinc salts effectively reduced the viral replication in the genome-length HCV RNA replication system but not in the subgenomic HCV replicon system.
  
  
  CONCLUSIONS
  We demonstrated that zinc may play an important role as a negative regulator of HCV replication in genome-length HCV RNA-replicating cells. Zinc supplementation thus appears to offer a novel approach to the development of future strategies for the treatment of intractable chronic hepatitis C.
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Yuasa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Naganuma
authors.forename: Ken
authors.initials: K
authors.lastname: Sato
authors.forename: Masanori
authors.initials: M
authors.lastname: Ikeda
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kato
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takagi
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016679:Genome, Viral; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D058085:Iron Compounds / Q000494:pharmacology; D049410:Luciferases, Renilla / Q000037:antagonists & inhibitors; D012367:RNA, Viral / Q000037:antagonists & inhibitors*; D012093:Replicon / Q000187:drug effects; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D014764:Viral Proteins / Q000037:antagonists & inhibitors; D014779:Virus Replication / Q000187:drug effects*; D017967:Zinc Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
chemical_list: D003603:Cytotoxins; D016898:Interferon-alpha; D058085:Iron Compounds; D049410:Luciferases, Renilla; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; D017967:Zinc Compounds; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase