Hepatitis B virus mutations associated with fulminant hepatitis induce apoptosis in primary tupaia hepatocytes

Thomas F. Baumert, Chun Yang, Peter Schürmann, Josef Köck, Christian Ziegler, Carsten Grüllich, Michael Nassal, T. Jake Liang, Hubert E. Blum, Fritz Von Weizsäcker

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Abstract

Hepatitis B virus (HBV) core promoter mutations have been implicated in the pathogenesis of fulminant hepatitis B. Due to the limited availability of primary human hepatocytes, the functional characterization of HBV mutants has been performed predominantly in transformed cells, which may not represent ideal model systems for studying virus-cell interactions. We and others have shown that primary hepatocytes of the tree shrew Tupaia belangen support HBV infection and replication. In this study, we used primary Tupaia hepatocytes to analyze the phenotype of two HBV core promoter mutations that have been associated with a clinical outbreak of fetal fulminant hepatitis. Similar to previous findings in human hepatoma cells, the HBV core promoter mutations resulted in enhanced viral replication and core expression. Surprisingly, however, the presence of the mutations had a marked effect on hepatocyte viability not previously observed in hepatoma cells. Reduced cell viability was Found to be due to the induction of apoptosis, as evidenced by caspase-3 activation and nuclear fragmentation. In conclusion, HBV mutants exhibit a novel phenotype in primary hepatocytes distinctly different from previous findings in hepatoma cell lines. This phenotype may have important implications for the understanding of the fulminant clinical course associated with HBV mutations.

Original languageEnglish (US)
Pages (from-to)247-256
Number of pages10
JournalHepatology
Volume41
Issue number2
DOIs
StatePublished - Feb 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Hepatology

Cite this

Baumert, T. F., Yang, C., Schürmann, P., Köck, J., Ziegler, C., Grüllich, C., Nassal, M., Liang, T. J., Blum, H. E., & Von Weizsäcker, F. (2005). Hepatitis B virus mutations associated with fulminant hepatitis induce apoptosis in primary tupaia hepatocytes. Hepatology, 41(2), 247-256. https://doi.org/10.1002/hep.20553