A CD8+ T cell immune evasion protein specific to Epstein-Barr virus and its close relatives in Old World primates

Andrew D. Hislop, Maaike E. Ressing, Daphne Van Leeuwen, Victoria A. Pudney, Daniëlle Horst, Danijela Koppers-Lalic, Nathan P. Croft, Jacques J. Neefjes, Alan B. Rickinson, Emmanuel J.H.J. Wiertz

Research output: Contribution to journalArticleResearchpeer-review

Abstract

γ1-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 α-and β-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 γ1-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 γ1- 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. JEM

Original languageEnglish
Pages (from-to)1863-1873
Number of pages11
JournalJournal of Experimental Medicine
Volume204
Issue number8
DOIs
Publication statusPublished - 6 Aug 2007

Cite this

Hislop, A. D., Ressing, M. E., Van Leeuwen, D., Pudney, V. A., Horst, D., Koppers-Lalic, D., ... Wiertz, E. J. H. J. (2007). A CD8+ T cell immune evasion protein specific to Epstein-Barr virus and its close relatives in Old World primates. Journal of Experimental Medicine, 204(8), 1863-1873. https://doi.org/10.1084/jem.20070256
Hislop, Andrew D. ; Ressing, Maaike E. ; Van Leeuwen, Daphne ; Pudney, Victoria A. ; Horst, Daniëlle ; Koppers-Lalic, Danijela ; Croft, Nathan P. ; Neefjes, Jacques J. ; Rickinson, Alan B. ; Wiertz, Emmanuel J.H.J. / A CD8+ T cell immune evasion protein specific to Epstein-Barr virus and its close relatives in Old World primates. In: Journal of Experimental Medicine. 2007 ; Vol. 204, No. 8. pp. 1863-1873.
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abstract = "γ1-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 α-and β-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 γ1-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 γ1- 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. JEM",
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Hislop, AD, Ressing, ME, Van Leeuwen, D, Pudney, VA, Horst, D, Koppers-Lalic, D, Croft, NP, Neefjes, JJ, Rickinson, AB & Wiertz, EJHJ 2007, 'A CD8+ T cell immune evasion protein specific to Epstein-Barr virus and its close relatives in Old World primates', Journal of Experimental Medicine, vol. 204, no. 8, pp. 1863-1873. https://doi.org/10.1084/jem.20070256

A CD8+ T cell immune evasion protein specific to Epstein-Barr virus and its close relatives in Old World primates. / Hislop, Andrew D.; Ressing, Maaike E.; Van Leeuwen, Daphne; Pudney, Victoria A.; Horst, Daniëlle; Koppers-Lalic, Danijela; Croft, Nathan P.; Neefjes, Jacques J.; Rickinson, Alan B.; Wiertz, Emmanuel J.H.J.

In: Journal of Experimental Medicine, Vol. 204, No. 8, 06.08.2007, p. 1863-1873.

Research output: Contribution to journalArticleResearchpeer-review

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AB - γ1-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 α-and β-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 γ1-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 γ1- 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. JEM

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