Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 1429K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hislop, A. D. Articles by Wiertz, E. J.H.J. Search for Related Content PubMed PubMed Citation Articles by Hislop, A. D. Articles by Wiertz, E. J.H.J. Related Collections Related Article Social Bookmarking                            What's this?

¹ Cancer Research UK Institute for Cancer Studies and MRC Centre for Immune Regulation, University of Birmingham, Edgbaston, Birmingham, B15 2TT, England, UK
² Department of Medical Microbiology, Leiden University Medical Center, 2300 RC Leiden, Netherlands
³ Division of Tumor Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands

CORRESPONDENCE Alan B. Rickinson: A.B.Rickinson{at}bham.ac.uk

1-Herpesviruses such as Epstein-Barr virus (EBV) have a unique ability to amplify virus loads in vivo through latent growth-transforming infection. Whether they, like - and ß-herpesviruses, have been driven to actively evade immune detection of replicative (lytic) infection remains a moot point. We were prompted to readdress this question by recent work (Pudney, V.A., A.M. Leese, A.B. Rickinson, and A.D. Hislop. 2005. J. Exp. Med. 201:349–360; Ressing, M.E., S.E. Keating, D. van Leeuwen, D. Koppers-Lalic, I.Y. Pappworth, E.J.H.J. Wiertz, and M. Rowe. 2005. J. Immunol. 174:6829–6838) showing that, as EBV-infected cells move through the lytic cycle, their susceptibility to EBV-specific CD8⁺ T cell recognition falls dramatically, concomitant with a reductions in transporter associated with antigen processing (TAP) function and surface human histocompatibility leukocyte antigen (HLA) class I expression. Screening of genes that are unique to EBV and closely related 1-herpesviruses of Old World primates identified an early EBV lytic cycle gene, BNLF2a, which efficiently blocks antigen-specific CD8⁺ T cell recognition through HLA-A–, HLA-B–, and HLA-C–restricting alleles when expressed in target cells in vitro. The small (60–amino acid) BNLF2a protein mediated its effects through interacting with the TAP complex and inhibiting both its peptide- and ATP-binding functions. Furthermore, this targeting of the major histocompatibility complex class I pathway appears to be conserved among the BNLF2a homologues of Old World primate 1-herpesviruses. Thus, even the acquisition of latent cycle genes endowing unique growth-transforming ability has not liberated these agents from evolutionary pressure to evade CD8⁺ T cell control over virus replicative foci.

A.D. Hislop and M.E. Ressing contributed equally to this work.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Article

EBV covers its tracks

Hema Bashyam
J. Exp. Med. 2007 204: 1733. [Full Text] [PDF]

This article has been cited by other articles:

• Stevenson, P. G., Simas, J. P., Efstathiou, S. (2009). Immune control of mammalian gamma-herpesviruses: lessons from murid herpesvirus-4. J. Gen. Virol. 90: 2317-2330 [Abstract] [Full Text]  
• Bell, M. J., Abbott, R. J. M., Croft, N. P., Hislop, A. D., Burrows, S. R. (2009). An HLA-A2-Restricted T-Cell Epitope Mapped to the BNLF2a Immune Evasion Protein of Epstein-Barr Virus That Inhibits TAP. J. Virol. 83: 2783-2788 [Abstract] [Full Text]  
• Horst, D., van Leeuwen, D., Croft, N. P., Garstka, M. A., Hislop, A. D., Kremmer, E., Rickinson, A. B., Wiertz, E. J. H. J., Ressing, M. E. (2009). Specific Targeting of the EBV Lytic Phase Protein BNLF2a to the Transporter Associated with Antigen Processing Results in Impairment of HLA Class I-Restricted Antigen Presentation. J. Immunol. 182: 2313-2324 [Abstract] [Full Text]  
• Wu, L., Fossum, E., Joo, C. H., Inn, K.-S., Shin, Y. C., Johannsen, E., Hutt-Fletcher, L. M., Hass, J., Jung, J. U. (2009). Epstein-Barr Virus LF2: an Antagonist to Type I Interferon. J. Virol. 83: 1140-1146 [Abstract] [Full Text]  
• Verweij, M. C., Koppers-Lalic, D., Loch, S., Klauschies, F., de la Salle, H., Quinten, E., Lehner, P. J., Mulder, A., Knittler, M. R., Tampe, R., Koch, J., Ressing, M. E., Wiertz, E. J. H. J. (2008). The Varicellovirus UL49.5 Protein Blocks the Transporter Associated with Antigen Processing (TAP) by Inhibiting Essential Conformational Transitions in the 6+6 Transmembrane TAP Core Complex. J. Immunol. 181: 4894-4907 [Abstract] [Full Text]  
• 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]  
• Loch, S., Klauschies, F., Scholz, C., Verweij, M. C., Wiertz, E. J. H. J., Koch, J., Tampe, R. (2008). Signaling of a Varicelloviral Factor across the Endoplasmic Reticulum Membrane Induces Destruction of the Peptide-loading Complex and Immune Evasion. J. Biol. Chem. 283: 13428-13436 [Abstract] [Full Text]  
• Dugan, G. E., Hewitt, E. W. (2008). Structural and Functional Dissection of the Human Cytomegalovirus Immune Evasion Protein US6. J. Virol. 82: 3271-3282 [Abstract] [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]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS