title: Mitochondrial electron transport inhibition in full genomic hepatitis C virus replicon cells is restored by reducing viral replication.
abstract: OBJECTIVE
  Hepatitis C virus (HCV) core protein has been shown to inhibit mitochondrial electron transport and to increase reactive oxygen species (ROS) in vitro and in vivo. The aim of this study was to investigate whether inhibiting HCV replication could restore the mitochondrial redox state and electron transport activity.
  
  
  METHODS
  We measured ROS, mitochondrial reduced glutathione content, and mitochondrial complex I, II, III and IV activities and protein expression in full genomic HCV replicon cells and cured cells that had been prepared by eliminating HCV RNA from replicon cells by interferon (IFN)-alpha treatment.
  
  
  RESULTS
  Cured cells had significantly lower ROS production and greater mitochondrial glutathione content than replicon cells. Complete inhibition of HCV replication by IFN-alpha restored complex I and IV activities by 20-30% (P<0.01) and complex I expression (P<0.05). Treatment with fluvastatin, one of the 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors, which is known to have anti-HCV activity, partially inhibited core protein expression and restored complex I activity in full genomic HCV replicon cells to a lesser degree (P<0.05).
  
  
  CONCLUSIONS
  Our results show that the mitochondrial redox state and electron transport activity can be restored by reducing HCV replication.
authors.affiliation: Department of Basic Laboratory Sciences, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Ando
authors.forename: Masaaki
authors.initials: M
authors.lastname: Korenaga
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hino
authors.forename: Masanori
authors.initials: M
authors.lastname: Ikeda
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kato
authors.forename: Sohji
authors.initials: S
authors.lastname: Nishina
authors.forename: Isao
authors.initials: I
authors.lastname: Hidaka
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D004579:Electron Transport; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D000077340:Fluvastatin; D016679:Genome, Viral; D005978:Glutathione / Q000378:metabolism; D016174:Hepacivirus / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism / Q000821:virology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D045222:Electron Transport Chain Complex Proteins; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D017382:Reactive Oxygen Species; D000077340:Fluvastatin; D005978:Glutathione