Immune tolerance split between hepatitis B virus precore and core proteins

Margaret Chen, Matti Sällberg, Janice Hughes, Joyce Jones, Luca G. Guidotti, Francis V. Chisari, Jean Noel Billaud, David R. Milich

Research output: Contribution to journalArticle

Abstract

The function of the hepatitis B virus (HBV) precore or HBeAg is largely unknown because it is not required for viral assembly, infection, or replication. However, the HBeAg does appear to play a role in viral persistence. It lias been suggested that the HBeAg may promote HBV chronicity by functioning as an immunoregulatory protein. As a model of chronic HBeAg exposure and to examine the tolerogenic potential of the HBV precore and core (HBcAg) proteins, HBc/HBeAg-transgenic (Tg) mice crossed with T cell receptor (TCR)-Tg mice expressing receptors for the HBc/HBeAgs (i.e., TCR-antigen double-Tg pairs) were produced. This study revealed three phenotypes of HBe/HBcAg-specific T-cell tolerance: (i) profound T-cell tolerance most likely mediated by clonal deletion, (ii) T-cell clonal ignorance, and (iii) nondeletional T-cell tolerance mediated by clonal anergy and dependent on the structure, location, and concentration of the tolerogen. The secreted HBeAg is significantly more efficient than the intracellular HBcAg at eliciting T-cell tolerance. The split T-cell tolerance between the HBeAg and the HBcAg and the clonal heterogeneity of HBc/HBeAg-specific T-cell tolerance may have significant implications for natural HBV infection and especially for precore-negative chronic hepatitis.

Original languageEnglish
Pages (from-to)3016-3027
Number of pages12
JournalJournal of Virology
Volume79
Issue number5
DOIs
Publication statusPublished - Mar 2005

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ASJC Scopus subject areas

  • Immunology

Cite this

Chen, M., Sällberg, M., Hughes, J., Jones, J., Guidotti, L. G., Chisari, F. V., Billaud, J. N., & Milich, D. R. (2005). Immune tolerance split between hepatitis B virus precore and core proteins. Journal of Virology, 79(5), 3016-3027. https://doi.org/10.1128/JVI.79.5.3016-3027.2005