HBx protein is indispensable for development of viraemia in human hepatocyte chimeric mice
- 10 March 2010
- journal article
- Published by Microbiology Society in Journal of General Virology
- Vol. 91 (7), 1854-1864
- https://doi.org/10.1099/vir.0.019224-0
Abstract
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 log10 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.This publication has 32 references indexed in Scilit:
- Enhancement of Hepatitis B Virus Replication by the Regulatory X Protein In Vitro and In VivoJournal of Virology, 2007
- Infection of human hepatocyte chimeric mouse with genetically engineered hepatitis B virusHepatology, 2005
- The Transcriptional Transactivation Function of HBx Protein Is Important for Its Augmentation Role in Hepatitis B Virus ReplicationJournal of Virology, 2005
- Near Completely Humanized Liver in Mice Shows Human-Type Metabolic Responses to DrugsThe American Journal of Pathology, 2004
- Identification of rare polymerase variants of hepatitis B virus using a two-stage PCR with peptide nucleic acid clampingJournal of Medical Virology, 2004
- Calcium Signaling by HBx Protein in Hepatitis B Virus DNA ReplicationScience, 2001
- Correct binding of viral X protein to UVDDB-p127 cellular protein is critical for efficient infection by hepatitis B virusesOncogene, 2000
- Hepatitis B Virus BiologyMicrobiology and Molecular Biology Reviews, 2000
- Expression of hepatitis B virus X protein in HBV-infected human livers and hepatocellular carcinomasHepatology, 1998
- Hepatic expression of the woodchuck hepatitis virus X-antigen during acute and chronic infection and detection of a woodchuck hepatitis virus X-antigen antibody responseHepatology, 1997