Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein

Gastroenterology. 2002 Feb;122(2):366-75. doi: 10.1053/gast.2002.30983.


Background & aims: The mechanisms of liver injury in chronic hepatitis C virus (HCV) infection are poorly understood. Indirect evidence suggests that oxidative stress and mitochondrial injury play a role. The aim of this study was to determine if the HCV core protein itself alters mitochondrial function and contributes to oxidative stress.

Methods: HCV core protein was expressed in 3 different cell lines, and reactive oxygen species (ROS) and lipid peroxidation products were measured.

Results: Core expression uniformly increased ROS. In 2 inducible expression systems, core protein also increased lipid peroxidation products and induced antioxidant gene expression as well. A mitochondrial electron transport inhibitor prevented the core-induced increase in ROS. A fraction of the expressed core protein localized to the mitochondria and was associated with redistribution of cytochrome c from mitochondrial to cytosolic fractions. Sensitivity to oxidative stress was also seen in HCV transgenic mice in which increased intrahepatic lipid peroxidation products occurred in response to carbon tetrachloride.

Conclusions: Oxidative injury occurs as a direct result of HCV core protein expression both in vitro and in vivo and may involve a direct effect of core protein on mitochondria. These results provide new insight into the pathogenesis of hepatitis C and provide an experimental rationale for investigation of antioxidant therapy.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Carcinoma, Hepatocellular
  • Cytochrome c Group / metabolism
  • Gene Expression Regulation, Viral
  • Hepatitis C, Chronic / metabolism*
  • Hepatocytes / cytology
  • Hepatocytes / metabolism
  • Hepatocytes / virology
  • Humans
  • Lipid Peroxidation / physiology
  • Liver / metabolism
  • Liver Neoplasms
  • Mice
  • Mice, Transgenic
  • Mitochondria / metabolism*
  • Mitochondria / virology
  • Oxidative Stress / physiology
  • Reactive Oxygen Species / metabolism
  • Tumor Cells, Cultured
  • Viral Core Proteins / genetics*
  • Viral Core Proteins / metabolism*


  • Antioxidants
  • Cytochrome c Group
  • Reactive Oxygen Species
  • Viral Core Proteins
  • nucleocapsid protein, Hepatitis C virus