The hepatitis B virus X protein transactivates viral core gene expression in vivo

J Virol. 1999 Dec;73(12):10399-405. doi: 10.1128/JVI.73.12.10399-10405.1999.

Abstract

The function of the X protein in the life cycle of mammalian hepadnaviruses is unclear. Based on tissue culture experiments it has been suggested that this protein represents a transcriptional transactivator which might be essential for the expression of the viral core gene. Here we have examined whether the activity of the human hepatitis B virus (HBV) core gene in vivo depends on X coexpression. To this end we compared core gene expression between four lineages of transgenic mice carrying the HBV core gene in cis arrangement with the X gene (cex lineage) and six lineages containing a modified construct in which the start codon of the X gene had been deleted (ce lineage). Whereas all cex lineages consistently exhibited a high-level hepatic core gene expression, the liver-specific core gene expression pattern of the ce lineages was heterogenous with four lineages virtually not expressing the core gene. This defect was due to a strongly reduced transcription since no core mRNA could be detected by Northern blotting. To test whether core gene expression could be restored by providing an intact X gene in trans, we crossbred mice of two lines which expressed no core mRNA or core protein with transgenic mice expressing the X-gene product under the transcriptional regulation of the liver-specific major-urinary-protein promoter/enhancer (MUP-X mice). The introduction of the MUP-X transgene induced core mRNA expression and core protein biosynthesis in the livers of the double-transgenic mice. This demonstrates that the X-gene product has the capacity to transactivate HBV core gene expression in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation, Viral*
  • Hepatitis B Core Antigens / genetics*
  • Hepatitis B virus / genetics*
  • Humans
  • Liver / pathology
  • Liver / virology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Transgenic
  • RNA, Messenger / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcriptional Activation*
  • Transgenes
  • Viral Regulatory and Accessory Proteins

Substances

  • Hepatitis B Core Antigens
  • RNA, Messenger
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein