HBx protein is indispensable for development of viraemia in human hepatocyte chimeric mice

J Gen Virol. 2010 Jul;91(Pt 7):1854-64. doi: 10.1099/vir.0.019224-0. Epub 2010 Mar 10.


The non-structural X protein, HBx, of hepatitis B virus (HBV) is assumed to play an important role in HBV replication. Woodchuck hepatitis virus X protein is indispensable for virus replication, but the duck hepatitis B virus X protein is not. In this study, we investigated whether the HBx protein is indispensable for HBV replication in vivo using human hepatocyte chimeric mice. HBx-deficient (HBx-def) HBV was generated in HepG2 cells by transfection with an overlength HBV genome. Human hepatocyte chimeric mice were infected with HBx-def HBV with or without hepatic HBx expression by hydrodynamic injection of HBx expression plasmids. Serum virus levels and HBV sequences were determined with mice sera. The generated HBx-def HBV peaked in the sucrose density gradient at points equivalent to the generated HBV wild type and the virus in a patient's serum. HBx-def HBV-injected mice developed measurable viraemia only in continuously HBx-expressed liver. HBV DNA in the mouse serum increased up to 9 log(10) copies ml(-1) and the viraemia persisted for more than 2 months. Strikingly, all revertant viruses had nucleotide substitutions that enabled the virus to produce the HBx protein. It was concluded that the HBx protein is indispensable for HBV replication and could be a target for antiviral therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chimera / genetics*
  • Gene Expression Regulation, Viral / physiology
  • Hepatitis B / virology*
  • Hepatitis B virus / physiology*
  • Hepatocytes / metabolism*
  • Hepatocytes / virology*
  • Humans
  • Mice
  • Time Factors
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Viral Regulatory and Accessory Proteins
  • Viremia
  • Virus Replication


  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein