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 Michalak, T. I.
Right arrow Articles by Churchill, N. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Michalak, T. I.
Right arrow Articles by Churchill, N. D.

 Previous Article  |  Next Article 

Journal of Virology, May 2000, p. 4483-4494, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Posttranscriptional Inhibition of Class I Major Histocompatibility Complex Presentation on Hepatocytes and Lymphoid Cells in Chronic Woodchuck Hepatitis Virus Infection

Tomasz I. Michalak,1,2,* Paul D. Hodgson,1 and Norma D. Churchill1

Molecular Virology and Hepatology Research, Division of Basic Medical Sciences,1 and Division of Pathology,2 Faculty of Medicine, Health Sciences Centre, Memorial University of Newfoundland, St. John's, Newfoundland A1B 3V6, Canada

Received 15 November 1999/Accepted 17 February 2000

Woodchuck hepatitis virus (WHV), similar to human hepatitis B virus, causes acute liver inflammation that can progress to chronic hepatitis and hepatocellular carcinoma. WHV also invades cells of the host lymphatic system, where it persists for life. We report here that acute and chronic hepadnavirus hepatitis is characterized by a profound difference in the expression of class I major histocompatibility complex (MHC) molecules on the surface of infected hepatocytes and, notably, lymphoid cells. While acute WHV infection is accompanied by the enhanced hepatocyte surface presentation of class I MHC antigen and upregulated transcription of the relevant hepatic genes, inhibition of class I antigen display on liver cells is a uniform hallmark of chronic WHV infection. This inhibition in chronic hepatitis occurs despite augmented (as in acute infection) expression of hepatic genes for class I MHC heavy chain, beta 2-microglobulin, and transporters associated with antigen processing (TAP1 and TAP2). Further, the class I antigen inhibition is not related to the histological severity of hepatocellular injury, the extent of lymphocytic infiltrations, the level of intrahepatic gamma interferon induction, or the hepatic WHV load. Importantly, the antigen expression is also inhibited on organ lymphoid cells of chronically infected hosts. The results obtained in this study demonstrate that the defective presentation of class I MHC molecules on cells supporting persistent WHV replication is due to viral posttranscriptional interference. This event may diminish the susceptibility of infected hepatocytes to virus-specific T-cell-mediated elimination, hinder virus clearance, and deregulate the class I MHC-dependent functions of the host immune system. This multifarious effect could be critical for perpetuation of liver damage and evasion of the antiviral immunological surveillance in chronic infection and therefore could be supportive of hepadnavirus persistence.

* Corresponding author. Mailing address: Molecular Virology and Hepatology Research, Division of Basic Medical Sciences, Faculty of Medicine, Health Sciences Centre, Memorial University of Newfoundland, St. John's, NFLD, Canada A1B 3V6. Phone: (709) 737-7301 (office) or (709) 737-7214 (lab). Fax: (709) 737-2228. E-mail: timich{at}morgan.ucs.mun.ca.

Journal of Virology, May 2000, p. 4483-4494, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Dougherty, A. M., Guo, H., Westby, G., Liu, Y., Simsek, E., Guo, J.-T., Mehta, A., Norton, P., Gu, B., Block, T., Cuconati, A. (2007). A Substituted Tetrahydro-Tetrazolo-Pyrimidine Is a Specific and Novel Inhibitor of Hepatitis B Virus Surface Antigen Secretion. Antimicrob. Agents Chemother. 51: 4427-4437 [Abstract] [Full Text]  
  • Wang, J., Gujar, S. A., Cova, L., Michalak, T. I. (2007). Bicistronic Woodchuck Hepatitis Virus Core and Gamma Interferon DNA Vaccine Can Protect from Hepatitis but Does Not Elicit Sterilizing Antiviral Immunity. J. Virol. 81: 903-916 [Abstract] [Full Text]  
  • MacParland, S. A., Pham, T. N. Q., Gujar, S. A., Michalak, T. I. (2006). De novo infection and propagation of wild-type Hepatitis C virus in human T lymphocytes in vitro. J. Gen. Virol. 87: 3577-3586 [Abstract] [Full Text]  
  • Wang, J., Michalak, T. I. (2006). Inhibition by woodchuck hepatitis virus of class I major histocompatibility complex presentation on hepatocytes is mediated by virus envelope pre-s2 protein and can be reversed by treatment with gamma interferon.. J. Virol. 80: 8541-8553 [Abstract] [Full Text]  
  • Fiedler, M., Rodicker, F., Salucci, V., Lu, M., Aurisicchio, L., Dahmen, U., Jun, L., Dirsch, O., Putzer, B. M., Palombo, F., Roggendorf, M. (2004). Helper-Dependent Adenoviral Vector-Mediated Delivery of Woodchuck-Specific Genes for Alpha Interferon (IFN-{alpha}) and IFN-{gamma}: IFN-{alpha} but Not IFN-{gamma} Reduces Woodchuck Hepatitis Virus Replication in Chronic Infection In Vivo. J. Virol. 78: 10111-10121 [Abstract] [Full Text]  
  • Michalak, T. I., Mulrooney, P. M., Coffin, C. S. (2004). Low Doses of Hepadnavirus Induce Infection of the Lymphatic System That Does Not Engage the Liver. J. Virol. 78: 1730-1738 [Abstract] [Full Text]  
  • Yoo, J.-Y., Desiderio, S. (2003). Innate and acquired immunity intersect in a global view of the acute-phase response. Proc. Natl. Acad. Sci. USA 100: 1157-1162 [Abstract] [Full Text]  
  • Mulrooney, P. M., Michalak, T. I. (2002). Quantitative Detection of Hepadnavirus-Infected Lymphoid Cells by In Situ PCR Combined with Flow Cytometry: Implications for the Study of Occult Virus Persistence. J. Virol. 77: 970-979 [Abstract] [Full Text]  
  • Lu, M., Lohrengel, B., Hilken, G., Kemper, T., Roggendorf, M. (2002). Woodchuck Gamma Interferon Upregulates Major Histocompatibility Complex Class I Transcription but Is Unable To Deplete Woodchuck Hepatitis Virus Replication Intermediates and RNAs in Persistently Infected Woodchuck Primary Hepatocytes. J. Virol. 76: 58-67 [Abstract] [Full Text]  
  • Putzer, B. M., Stiewe, T., Rodicker, F., Schildgen, O., Ruhm, S., Dirsch, O., Fiedler, M., Damen, U., Tennant, B., Scherer, C., Graham, F. L., Roggendorf, M. (2001). Large Nontransplanted Hepatocellular Carcinoma in Woodchucks: Treatment With Adenovirus-Mediated Delivery of Interleukin 12/B7.1 Genes. JNCI J Natl Cancer Inst 93: 472-479 [Abstract] [Full Text]  
  • Lew, Y.-Y., Michalak, T. I. (2001). In Vitro and In Vivo Infectivity and Pathogenicity of the Lymphoid Cell-Derived Woodchuck Hepatitis Virus. J. Virol. 75: 1770-1782 [Abstract] [Full Text]  
  • Reignat, S., Webster, G. J.M., Brown, D., Ogg, G. S., King, A., Seneviratne, S. L., Dusheiko, G., Williams, R., Maini, M. K., Bertoletti, A. (2002). Escaping High Viral Load Exhaustion: CD8 Cells with Altered Tetramer Binding in Chronic Hepatitis B Virus Infection. JEM 195: 1089-1101 [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»