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 Guerreiro-Cacais, A. O.
Right arrow Articles by Levitsky, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Guerreiro-Cacais, A. O.
Right arrow Articles by Levitsky, V.

 Previous Article  |  Next Article 

Journal of Virology, February 2007, p. 1390-1400, Vol. 81, No. 3
0022-538X/07/$08.00+0     doi:10.1128/JVI.01999-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Inhibition of Heavy Chain and ß2-Microglobulin Synthesis as a Mechanism of Major Histocompatibility Complex Class I Downregulation during Epstein-Barr Virus Replication{triangledown}

Andre Ortlieb Guerreiro-Cacais,1,4,{dagger} Mehmet Uzunel,3 Jelena Levitskaya,2,4,{dagger} and Victor Levitsky1,4*

IRIS Center for Strategic Research, Department of Microbiology, Tumor and Cell Biology,1 Oncology and Pathology Department, Cancer Centrum Karolinska, Karolinska Institute, Stockholm, Sweden,2 Department of Clinical Immunology, Karolinska University Hospital, Huddinge 141 86, Sweden,3 Division of Biomedical Sciences, Johns Hopkins Singapore, Singapore4

Received 14 September 2006/ Accepted 5 November 2006

The mechanisms of major histocompatibility complex (MHC) class I downregulation during Epstein-Barr virus (EBV) replication are not well characterized. Here we show that in several cell lines infected with a recombinant EBV strain encoding green fluorescent protein (GFP), the virus lytic cycle coincides with GFP expression, which thus can be used as a marker of virus replication. EBV replication resulted in downregulation of MHC class II and all classical MHC class I alleles independently of viral DNA synthesis or late gene expression. Although assembled MHC class I complexes, the total pool of heavy chains, and ß2-microglobulin (ß2m) were significantly downregulated, free class I heavy chains were stabilized at the surface of cells replicating EBV. Calnexin expression was increased in GFP+ cells, and calnexin and calreticulin accumulated at the cell surface that could contribute to the stabilization of class I heavy chains. Decreased expression levels of another chaperone, ERp57, and TAP2, a transporter associated with antigen processing and presentation, correlated with delayed kinetics of MHC class I maturation. Levels of both class I heavy chain and ß2m mRNA were reduced, and metabolic labeling experiments demonstrated a very low rate of class I heavy chain synthesis in lytically infected cells. MHC class I and MHC class II downregulation was mimicked by pharmacological inhibition of protein synthesis in latently infected cells. Our data suggest that although several mechanisms may contribute to MHC class I downregulation in the course of EBV replication, inhibition of MHC class I synthesis plays the primary role in the process.

* Corresponding author. Present address: Nobels väg 16, 17177 Stockholm, Sweden. Phone: 46-8-52486981. Fax: 46-8-331339. E-mail: Victor.Levitsky{at}ki.se.

{triangledown} Published ahead of print on 15 November 2006.

{dagger} Present address: Division of Biomedical Sciences, Johns Hopkins in Singapore, 31 Biopolis Way #02-01, Nanos Building, Singapore 138669.

Journal of Virology, February 2007, p. 1390-1400, Vol. 81, No. 3
0022-538X/07/$08.00+0     doi:10.1128/JVI.01999-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Roder, G., Geironson, L., Bressendorff, I., Paulsson, K. (2008). Viral Proteins Interfering with Antigen Presentation Target the Major Histocompatibility Complex Class I Peptide-Loading Complex. J. Virol. 82: 8246-8252 [Full Text]  
  • Zuo, J., Thomas, W., van Leeuwen, D., Middeldorp, J. M., Wiertz, E. J. H. J., Ressing, M. E., Rowe, M. (2008). The DNase of Gammaherpesviruses Impairs Recognition by Virus-Specific CD8+ T Cells through an Additional Host Shutoff Function. J. Virol. 82: 2385-2393 [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»