A CD8+ T cell immune evasion protein specific to Epstein-Barr virus and its close relatives in Old World primates.
gamma 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 alpha- and beta-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 gamma 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 gamma 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.
Hislop
Andrew D
AD
Cancer Research UK Institute for Cancer Studies and MRC Centre for Immune Regulation, University of Birmingham, Edgbaston, Birmingham, B15 2TT, England, UK.
Ressing
Maaike E
ME
van Leeuwen
Daphne
D
Pudney
Victoria A
VA
Horst
Daniëlle
D
Koppers-Lalic
Danijela
D
Croft
Nathan P
NP
Neefjes
Jacques J
JJ
Rickinson
Alan B
AB
Wiertz
Emmanuel J H J
EJ
D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002520:Cercopithecidae; D003001:Cloning, Molecular; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006680:HLA Antigens / Q000737:chemistry / Q000378:metabolism; D006564:Herpesviridae / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D007107:Immune System / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D017386:Sequence Homology, Amino Acid
D006680:HLA Antigens; D010455:Peptides