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A function of the hepatitis B virus precore protein is to regulate the immune response to the core antigen

Academic Article
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Overview

authors

  • Chen, M. T.
  • Billaud, J. N.
  • Sallberg, M.
  • Guidotti, Luca
  • Chisari, Francis
  • Jones, J.
  • Hughes, J.
  • Milich, D. R.

publication date

  • October 2004

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • A unique characteristic of the hepatitis B virus is the production of a secreted form (precore or HBeAg) of the structural nucleocapsid (core or HBcAg). By using T cell receptor (TCR) transgenic (Tg) and TCR x HBc/HBeAg double- and triple-Tg pairs, we demonstrate that HBeAg elicits T cell tolerance, whereas HBcAg is nontolerogenic in this system. In fact, TCR x HBc double-Tg mice spontaneously seroconvert to IgG anti-HBc positivity at an early age. However, the presence of HBeAg in the serum of TCR x HBc x HBe triple-Tg mice prevents anti-HBc seroconversion. HBeAg mediates its immunoregulatory effect by eliciting tolerance in HBc/HBeAg-specific T cells. The results suggest that hepadnaviruses have retained a secretory form of the nucleoprotein because it functions as a T cell tolerogen and regulates the immune response to the intracellular nucleocapsid. This HBeAg-mediated immune regulation may predispose to chronicity during perinatal infections and prevent severe liver injury during adult infections.

subject areas

  • Adoptive Transfer
  • Animals
  • Clonal Anergy
  • Cytokines
  • Hepatitis B Antigens
  • Hepatitis B Core Antigens
  • Hepatitis B e Antigens
  • Hepatitis B virus
  • Liver
  • Mice
  • Mice, Transgenic
  • Protein Precursors
  • Receptors, Antigen, T-Cell
  • Recombinant Proteins
  • Spleen
  • T-Lymphocytes
  • Viral Core Proteins
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Identity

PubMed Central ID

  • PMC522042

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0406282101

PubMed ID

  • 15469922
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Additional Document Info

start page

  • 14913

end page

  • 14918

volume

  • 101

issue

  • 41

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