A Function of the Hepatitis B Virus Precore Protein Is to Regulate the Immune Response to the Core Antigen

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 × HBc/HBeAg double- and triple-Tg pairs, we demonstrate that HBeAg elicits T cell tolerance,...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2004-10, Vol.101 (41), p.14913-14918
Main Authors: Chen, Margaret T., Billaud, Jean-Noel, Sällberg, Matti, Guidotti, Luca G., Chisari, Francis V., Jones, Joyce, Hughes, Janice, Milich, David R.
Format: Article
Language:English
Subjects:
Adoptive Transfer
Animals
Antibodies
Antigens
Biological Sciences
Clonal Anergy
Cultured cells
Cytokines - analysis
Exercise tolerance
Hepatitis
Hepatitis antigens
Hepatitis B
Hepatitis B Antigens - immunology
Hepatitis B Core Antigens - immunology
Hepatitis B e Antigens - blood
Hepatitis B virus
Hepatitis B virus - immunology
Immune system
Infections
Liver
Liver - virology
Medicin och hälsovetenskap
Mice
Mice, Transgenic
Protein Precursors - immunology
Proteins
Receptors, Antigen, T-Cell - immunology
Recombinant Proteins - immunology
Spleen - immunology
Spleen - transplantation
Spleen cells
T cell antigen receptors
T lymphocytes
T-Lymphocytes - immunology
Transplantation tolerance
Viral Core Proteins - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 × 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 × 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 × HBc × 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0406282101