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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)14913-14918
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number41
DOIs
Publication statusPublished - Oct 12 2004

ASJC Scopus subject areas

  • General
  • Genetics

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