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Journal of Virology, December 1999, p. 10399-10405, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

The Hepatitis B Virus X Protein Transactivates Viral Core Gene Expression In Vivo

Kurt Reifenberg,1 Heike Wilts,1 Jürgen Löhler,2 Petra Nusser,1 Ralph Hanano,3 Luca G. Guidotti,4 Francis V. Chisari,4 and Hans-Jürgen Schlicht5,*

Laboratory Animal Research Unit,1 Department of Immunology,3 and Department of Virology,5 University of Ulm, 89081 Ulm, and Heinrich Pette Institute for Experimental Virology and Immunology, 20251 Hamburg,2 Germany, and Division of Experimental Pathology, Scripps Research Institute, La Jolla, California 920374

Received 2 September 1999/Accepted 7 September 1999

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.


* Corresponding author. Mailing address: Department of Virology, University of Ulm, Albert Einstein Allee 11, 89081 Ulm, Germany. Phone: 49-731-502-3340. Fax: 49-731-502-3337. E-mail: hans-juergen.schlicht{at}dezernat-6.uni-ulm.de.


Journal of Virology, December 1999, p. 10399-10405, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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