This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Robek, M. D.
Right arrow Articles by Chisari, F. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Robek, M. D.
Right arrow Articles by Chisari, F. V.

 Previous Article  |  Next Article 

Journal of Virology, January 2007, p. 483-491, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.01779-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Role of Immunoproteasome Catalytic Subunits in the Immune Response to Hepatitis B Virus{triangledown}

Michael D. Robek,1* Mayra L. Garcia,1 Bryan S. Boyd,2 and Francis V. Chisari2

Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510,1 Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 920372

Received 16 August 2006/ Accepted 20 October 2006

Inhibition of hepatitis B virus (HBV) replication and viral clearance from an infected host requires both the innate and adaptive immune responses. Expression of interferon (IFN)-inducible proteasome catalytic and regulatory subunits correlates with the IFN-{alpha}/ß- and IFN-{gamma}-mediated noncytopathic inhibition of HBV in transgenic mice and hepatocytes, as well as with clearance of the virus in acutely infected chimpanzees. The immunoproteasome catalytic subunits LMP2 and LMP7 alter proteasome specificity and influence the pool of peptides available for presentation by major histocompatibility complex class I molecules. We found that these subunits influenced both the magnitude and specificity of the CD8 T-cell response to the HBV polymerase and envelope proteins in immunized HLA-A2-transgenic mice. We also examined the role of LMP2 and LMP7 in the IFN-{alpha}/ß- and IFN-{gamma}-mediated inhibition of virus replication using HBV transgenic mice and found that they do not play a direct role in this process. These results demonstrate the ability of the IFN-induced proteasome catalytic subunits to shape the HBV-specific CD8 T-cell response and thus potentially influence the progression of infection to acute or chronic disease. In addition, these studies identify a potential key role for IFN in regulating the adaptive immune response to HBV through alterations in viral antigen processing.

* Corresponding author. Mailing address: Department of Pathology, Yale University School of Medicine, P.O. Box 208023, 310 Cedar Street LH315A, New Haven, CT 06520-8023. Phone: (203) 785-6174. Fax: (203) 785-6127. E-mail: michael.robek{at}yale.edu.

{triangledown} Published ahead of print on 1 November 2006.

Journal of Virology, January 2007, p. 483-491, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.01779-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Garcia, M. L., Byfield, R., Robek, M. D. (2009). Hepatitis B Virus Replication and Release Are Independent of Core Lysine Ubiquitination. J. Virol. 83: 4923-4933 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»