BACKGROUND/AIM: 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.
BACKGROUND/AIM: 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: Donna N Douglas; Christopher Hao Pu; Jamie T Lewis; Rakesh Bhat; Anwar Anwar-Mohamed; Michael Logan; Garry Lund; William R Addison; Richard Lehner; Norman M Kneteman Journal: J Biol Chem Date: 2015-12-01 Impact factor: 5.157
Authors: Sandra Pisonero-Vaquero; María V García-Mediavilla; Francisco Jorquera; Pedro L Majano; Marta Benet; Ramiro Jover; Javier González-Gallego; Sonia Sánchez-Campos Journal: Lab Invest Date: 2014-02-03 Impact factor: 5.662
Authors: Alexander V Ivanov; Birke Bartosch; Olga A Smirnova; Maria G Isaguliants; Sergey N Kochetkov Journal: Viruses Date: 2013-01-28 Impact factor: 5.048