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A function of the hepatitis B virus precore protein is to regulate the immune response to the core antigen
Open accessAbstract
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.
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Citations
Cited by
Immunology of hepatitis B virus and hepatitis C virus infection
Rehermann, B., & Nascimbeni, M. (2005) · Nature Reviews Immunology · doi:10.1038/nri1573 · Cited by 1,627
Immunobiology and pathogenesis of hepatitis B virus infection
Iannacone, M., & Guidotti, L. G. (2022) · Nature Reviews Immunology · doi:10.1038/s41577-021-00549-4 · Cited by 520
Self-citationWooddell, C. I., Yuen, M.-F., Chan, H. L.-Y., Gish, R. G., Locarnini, S. A., Chavez, D., Ferrari, C., Given, B. D., Hamilton, J., Kanner, S. B., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aan0241 · Cited by 490
Hepatitis B virus X protein is essential to initiate and maintain virus replication after infection
Lucifora, J., Arzberger, S., Durantel, D., Belloni, L., Strubin, M., Levrero, M., Zoulim, F., Hantz, O., & Protzer, U. (2011) · Journal of Hepatology · doi:10.1016/j.jhep.2011.02.015 · Cited by 481
Overview of hepatitis B viral replication and genetic variability
Tong, S., & Revill, P. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.01.027 · Cited by 417
Metadata
- Authors
- Chen, M. T., Billaud, J.-N., Sällberg, M., Guidotti, L. G., Chisari, F. V., Jones, J., Hughes, J., & Milich, D. R.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2004-10-05
- Volume
- 101
- Issue
- 41
- Pages
- 14913-14918
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1978551768
- Cited by
- 241
- References
- 0
- FWCI
- 6.30
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Chen, M. T., Billaud, J.-N., Sällberg, M., Guidotti, L. G., Chisari, F. V., Jones, J., Hughes, J., & Milich, D. R. (2004). A function of the hepatitis B virus precore protein is to regulate the immune response to the core antigen. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0406282101
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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