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

Kurt Reifenberg, Heike Wilts, Jürgen Löhler, Petra Nusser, Ralph Hanano, Luca G. Guidotti, Francis V. Chisari, H. J. Schlicht

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)10399-10405
Number of pages7
JournalJournal of Virology
Volume73
Issue number12
Publication statusPublished - Dec 1999

    Fingerprint

ASJC Scopus subject areas

  • Immunology

Cite this

Reifenberg, K., Wilts, H., Löhler, J., Nusser, P., Hanano, R., Guidotti, L. G., Chisari, F. V., & Schlicht, H. J. (1999). The hepatitis B virus X protein transactivates viral core gene expression in vivo. Journal of Virology, 73(12), 10399-10405.