Mitochondrial electron transport inhibition in full genomic hepatitis C virus replicon cells is restored by reducing viral replication.
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.
Ando
Mie
M
Department of Basic Laboratory Sciences, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
Korenaga
Masaaki
M
Hino
Keisuke
K
Ikeda
Masanori
M
Kato
Nobuyuki
N
Nishina
Sohji
S
Hidaka
Isao
I
Sakaida
Isao
I
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*
D000998:Antiviral Agents; D045222:Electron Transport Chain Complex Proteins; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D017382:Reactive Oxygen Species; D000077340:Fluvastatin; D005978:Glutathione