Young L S, Dawson C W, Clark D, Rupani H, Busson P, Tursz T, Johnson A, Rickinson A B
Department of Cancer Studies, University of Birmingham, U.K.
J Gen Virol. 1988 May;69 ( Pt 5):1051-65. doi: 10.1099/0022-1317-69-5-1051.
Epstein-Barr virus (EBV), an agent with growth transforming potential for human B cells, is associated with certain B cell lymphomas in man and also with an epithelial tumour, undifferentiated nasopharyngeal carcinoma (NPC). Since B cell growth transformation is associated with the constitutive expression of a small number of EBV-coded latent proteins, the nuclear antigens EBNA 1, EBNA 2, EBNA 3 and EBNA-LP and the latent membrane protein (LMP), the present work sought to determine whether this same pattern of virus gene expression occurred in NPC. Tumour biopsies were taken from NPC patients from three areas of differing tumour incidence (Kenya, Algeria, Britain) and immediately snap-frozen, as were biopsies of non-EBV-related carcinomas for controls. Immunoblotting of PAGE-separated proteins with selected human sera identified 24 NPC biopsies clearly expressing EBNA 1. When the analysis was extended using selected human sera with antibodies against the other EBNAs, there was no detectable expression of EBNA 2, EBNA 3 or EBNA-LP in any of these 24 biopsies; their EBNA 2-negative status was confirmed using a monoclonal antibody (MAb) PE2 which was reactive in immunoblotting and in immunoprecipitation with EBNA 2A and EBNA 2B proteins. Similar experiments with two different LMP-specific MAbs, CS1 to 4 and S12, revealed heterogeneity between NPC biopsies; 9/24 biopsies were demonstrably LMP-positive, the degree of expression varying considerably between individual tumours in a manner which was not related to the level of EBNA 1 expression. None of the 24 NPC biopsies expressed detectable amounts of EBV lytic cycle antigens. A nude mouse-passaged NPC cell line, C15, likewise expressed EBNA 1 and LMP but none of the other EBV latent proteins nor lytic cycle antigens. This work identifies a novel type of EBV-cell interaction in NPC cells which is distinct from that seen in in vitro transformed B cell lines and from that seen to date in EBV-positive B cell lymphomas.
爱泼斯坦-巴尔病毒（EBV）是一种对人类B细胞具有生长转化潜能的病原体，与人类的某些B细胞淋巴瘤以及一种上皮性肿瘤——未分化鼻咽癌（NPC）有关。由于B细胞生长转化与少数EBV编码的潜伏蛋白的组成性表达有关，这些蛋白包括核抗原EBNA 1、EBNA 2、EBNA 3和EBNA-LP以及潜伏膜蛋白（LMP），因此本研究旨在确定这种相同的病毒基因表达模式是否也出现在鼻咽癌中。从三个肿瘤发病率不同的地区（肯尼亚、阿尔及利亚、英国）的鼻咽癌患者身上获取肿瘤活检组织，并立即速冻，同时获取非EBV相关癌的活检组织作为对照。用选定的人血清对聚丙烯酰胺凝胶电泳分离的蛋白质进行免疫印迹分析，鉴定出24份鼻咽癌活检组织明显表达EBNA 1。当使用针对其他EBNA的抗体的选定人血清进行进一步分析时，在这24份活检组织中均未检测到EBNA 2、EBNA 3或EBNA-LP的表达；使用在免疫印迹和与EBNA 2A及EBNA 2B蛋白的免疫沉淀反应中具有反应性的单克隆抗体（MAb）PE2，证实了它们的EBNA 2阴性状态。用两种不同的LMP特异性单克隆抗体CS1至4和S12进行的类似实验显示，鼻咽癌活检组织之间存在异质性；24份活检组织中有9份明显呈LMP阳性，个体肿瘤之间的表达程度差异很大，且与EBNA 1的表达水平无关。24份鼻咽癌活检组织中均未表达可检测量的EBV裂解周期抗原。一种在裸鼠中传代的鼻咽癌细胞系C15同样表达EBNA 1和LMP，但不表达其他EBV潜伏蛋白或裂解周期抗原。这项研究确定了鼻咽癌细胞中一种新型的EBV-细胞相互作用，这种相互作用不同于体外转化的B细胞系中所见的相互作用，也不同于迄今为止在EBV阳性B细胞淋巴瘤中所见的相互作用。
