EPSTEIN-BARR-VIRUS LATENT MEMBRANE-PROTEIN INHIBITS HUMAN EPITHELIAL-CELL DIFFERENTIATION
EPSTEIN-BARR-VIRUS LATENT MEMBRANE-PROTEIN INHIBITS HUMAN EPITHELIAL-CELL DIFFERENTIATION
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DOI：
10.1038/344777a0
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发表时间：
1990-04-19
期刊：
影响因子：
64.8
通讯作者：
YOUNG, LS
中科院分区：
文献类型：
--
作者：
DAWSON, CW;RICKINSON, AB;YOUNG, LS
EB病毒（EBV）是一种人类疱疹病毒，与两种相对罕见的B细胞淋巴瘤和一种更普遍的上皮恶性肿瘤（未分化鼻咽癌（NPC））密切相关。合适的培养系统的可用性允许详细分析EBV诱导的B淋巴细胞的生长转化，但对病毒-上皮细胞相互作用或病毒蛋白在NPC发病机制中的可能效应作用知之甚少。在这里，我们描述了一个实验系统，以监测引入病毒或细胞基因对人上皮细胞生长和分化的影响。我们用编码潜伏膜蛋白（LMP）的EBV基因转染了一种人上皮细胞系，该细胞系保留了体外正常角质形成细胞行为的几个特征，LMP是已知在NPC细胞中体内表达的仅有的两种病毒蛋白之一2 '3。LMP表达伴随着上皮细胞表面表型的变化，模仿在NPC细胞中观察到的表面变化，以及对分化信号的细胞反应的严重损害。LMP抑制终末分化的能力表明，鳞状上皮的EBV感染可能有助于NPC的多步骤发病机制。
EPSTEIN–BARR virus (EBV), a human herpesvirus, is strongly linked with two relatively rare forms of B-cell lymphoma and with a much more prevalent epithelial malignancy, undifferentiated nasopharyngeal carcinoma (NPC)1. The availability of suitable culture systems has allowed detailed analysis of EBV-induced growth transformation in B lymphocytes, but little is known about the virus–epithelial cell interaction or about the possible effector role of viral proteins in the pathogenesis of NPC. Here we describe an experimental system to monitor the effects of introduced viral or cellular genes upon human epithelial cell growth and differentiation. We transfected a human epithelial cell line, which retains several features of normal keratinocyte behaviourin vitro, with the EBV gene encoding latent membrane protein (LMP), one of only two viral proteins known to be expressed in NPC cellsin vivo2'3. LMP expression was accompanied by changes in the epithelial cell surface phenotype, mimicking surface changes observed in NPC cells, and by severe impairment of the cellular response to differentiation signals. The ability of LMP to inhibit terminal differentiation indicates a mechanism whereby EBV infection of squamous epithelium could contribute to the multi-step pathogenesis of NPC.