A CD8+ T cell immune evasion protein specific to Epstein-Barr virus and its close relatives in Old World primates.
A CD8+ T cell immune evasion protein specific to Epstein-Barr virus and its close relatives in Old World primates.
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DOI：
10.1084/jem.20070256
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发表时间：
2007-08-06
期刊：
影响因子：
--
通讯作者：
Wiertz EJ
中科院分区：
文献类型：
--
作者：
Hislop AD;Ressing ME;van Leeuwen D;Pudney VA;Horst D;Koppers-Lalic D;Croft NP;Neefjes JJ;Rickinson AB;Wiertz EJ
γ1-疱疹病毒如EB病毒（EBV）具有通过潜伏生长转化感染在体内扩增病毒载量的独特能力。它们是否像α-和β-疱疹病毒一样主动逃避复制（裂解）感染的免疫检测仍然是一个有争议的问题。最近的工作促使我们重新讨论这个问题（Pudney，V.A.，A.M. Leese，A.B. Rickinson和A.D. Hislop。2005. J. Exp. 201：349-360; Ressing，M.E.，S.E. Keating，D.货车Leeuwen，D. Koppers-Lalic，I.Y. Pappworth、E.J.H.J. Wiertz和M.罗2005. 174：6829-6838），显示了当EBV感染的细胞通过裂解周期时，它们对EBV特异性CD 8 + T细胞识别的敏感性急剧福尔斯，伴随着与抗原加工（TAP）功能和表面人组织相容性白细胞抗原（HLA）I类表达相关的转运蛋白的减少。对EBV和旧大陆灵长类动物的密切相关γ1-疱疹病毒特有的基因进行筛选，鉴定出早期EBV裂解周期基因BNLF 2a，其在体外靶细胞中表达时，通过HLA-A-、HLA-B-和HLA-C-限制性等位基因有效阻断抗原特异性CD 8 + T细胞识别。小的（60个氨基酸）BNLF 2a蛋白介导的作用，通过与TAP复合物相互作用，抑制其肽和ATP结合功能。此外，这种主要组织相容性复合体I类途径的靶向似乎在旧世界灵长类γ1-疱疹病毒的BNLF 2a同源物中是保守的。因此，即使获得了赋予独特生长转化能力的潜伏周期基因，也没有将这些药物从进化压力中解放出来，以逃避CD 8 + T细胞对病毒复制灶的控制。
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.
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影响因子：
5.4
作者：
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通讯作者：
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影响因子：
5.4
作者：
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影响因子：
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爱泼斯坦 - 巴尔病毒裂解循环抗原之间的CD8+免疫主导直接反映了抗原感染细胞中抗原的效率。
影响因子：
15.3
作者：
Pudney, VA;Leese, AM;Rickinson, AB;Hislop, AD
通讯作者：
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