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 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.
Chen
Margaret T
MT
Karolinska Institute and Swedish Institute for Infectious Disease Control, 171 82 Solna, Sweden.
Billaud
Jean-Noel
JN
Sällberg
Matti
M
Guidotti
Luca G
LG
Chisari
Francis V
FV
Jones
Joyce
J
Hughes
Janice
J
Milich
David R
DR
D019264:Adoptive Transfer; D000818:Animals; D017635:Clonal Anergy; D016207:Cytokines / Q000032:analysis; D006511:Hepatitis B Antigens / Q000276:immunology*; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000276:immunology*; D008099:Liver / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D011498:Protein Precursors / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000637:transplantation; D013601:T-Lymphocytes / Q000276:immunology; D014758:Viral Core Proteins / Q000276:immunology*
D016207:Cytokines; D006511:Hepatitis B Antigens; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens; D011498:Protein Precursors; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D014758:Viral Core Proteins