Immediate early and early lytic cycle proteins are frequent targets of the Epstein-Barr virus-induced cytotoxic T cell response.

Immediate early and early lytic cycle proteins are frequent targets of the Epstein-Barr virus-induced cytotoxic T cell response.
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DOI:
10.1084/jem.185.9.1605
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发表时间:
1997-05-05
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Rickinson AB
Rickinson AB
中科院分区:
其他
文献类型:
--
作者:
Steven NM;Annels NE;Kumar A;Leese AM;Kurilla MG;Rickinson AB

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EB病毒(EBV)是一种人γ-疱疹病毒,可建立非生产性(潜伏性)和生产性(裂解性)感染。虽然CD 8+细胞毒性T淋巴细胞(CTL)对潜伏感染细胞的反应是很好的特点,很少有人知道T细胞控制溶解性感染,这种不平衡在我们的理解掩盖了病毒复制性病变的重要性,在EBV疾病的发病机制的几个方面。目前的工作表明,传染性单核细胞增多症患者对EB病毒的初级CD 8 + CTL反应包含多种溶解性抗原特异性反应,其水平至少与针对潜伏抗原观察到的水平一样高;在CTL记忆中也可以检测到类似的反应。克隆分析揭示了个体对两种立即早期蛋白BZLF 1和BRLF 1的反应,以及对测试的六种早期蛋白中的三种(BMLF 1、BMRF 1和BALF 2)的反应。在一些情况下,这些CTL识别的肽表位和HLA限制性决定簇已经被定义,一个不寻常的特征是通过HLA-C等位基因限制的应答数量。这项工作有力地表明,EBV复制性病变在体内受到直接CTL控制,并且立即早期和早期蛋白质通常是免疫显性靶点。这与α-和β-疱疹病毒系统(单纯疱疹病毒、巨细胞病毒)中的结果形成对比,在α-和β-疱疹病毒系统中,病毒在裂解性感染期间干扰抗原加工途径,使立即早期和早期蛋白质的免疫原性低得多。γ-疱疹病毒通过潜伏生长转化感染在体内扩增病毒载量的独特能力可能使这些因子不太依赖于病毒复制作为成功定殖其宿主的手段。
Epstein-Barr virus (EBV), a human γ-herpesvirus, can establish both nonproductive (latent) and productive (lytic) infections. Although the CD8+ cytotoxic T lymphocyte (CTL) response to latently infected cells is well characterized, very little is known about T cell controls over lytic infection; this imbalance in our understanding belies the importance of virus-replicative lesions in several aspects of EBV disease pathogenesis. The present work shows that the primary CD8+ CTL response to EBV in infectious mononucleosis patients contains multiple lytic antigen-specific reactivities at levels at least as high as those seen against latent antigens; similar reactivities are also detectable in CTL memory. Clonal analysis revealed individual responses to the two immediate early proteins BZLF1 and BRLF1, and to three (BMLF1, BMRF1, and BALF2) of the six early proteins tested. In several cases, the peptide epitope and HLA-restricting determinant recognized by these CTLs has been defined, one unusual feature being the number of responses restricted through HLA-C alleles. The work strongly suggests that EBVreplicative lesions are subject to direct CTL control in vivo and that immediate early and early proteins are frequently the immunodominant targets. This contrasts with findings in α- and β-herpesvirus systems (herpes simplex, cytomegalovirus) where viral interference with the antigen-processing pathway during lytic infection renders immediate early and early proteins much less immunogenic. The unique capacity of γ-herpesvirus to amplify the viral load in vivo through a latent growth-transforming infection may have rendered these agents less dependent upon viral replication as a means of successfully colonizing their hosts.
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发表时间: 1991-09-01
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发表时间: 1994-09-01
影响因子: 3.8
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