Identification of functional differences between prototype Epstein-Barr virus-encoded LMP1 and a nasopharyngeal carcinoma-derived LMP1 in human epithelial cells
Identification of functional differences between prototype Epstein-Barr virus-encoded LMP1 and a nasopharyngeal carcinoma-derived LMP1 in human epithelial cells
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DOI：
10.1006/viro.2000.0344
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发表时间：
2000-06-20
期刊：
影响因子：
3.7
通讯作者：
Young, LS
中科院分区：
文献类型：
--
作者：
Dawson, CW;Eliopoulos, AG;Young, LS
EB病毒（EBV）毒株变异对病毒相关肿瘤发病机制的贡献仍不清楚。鉴于LMP 1在EBV诱导的转化中的核心作用，许多兴趣集中在LMP 1序列变异对信号传导途径和LMP 1表达的多个下游表型后果的影响上。在与鼻咽癌相关的EBV株中鉴定具有常见的10个氨基酸缺失和额外的点突变（以CAO-LMP 1分离株为代表）的LMP 1变体促使我们检查稳定原型B95.8-LMP 1和CAO-LMP 1表达对SCC 12 F人上皮细胞的表型和分化的影响。这两种形式的LMP 1能够诱导抗凋亡A20蛋白的表达，并提供保护，从肿瘤坏死因子-CT诱导的细胞毒性。尽管B95.8-LMP 1在SCC 12 F细胞中诱导生长抑制、某些细胞表面分子（CD 40、CD 44和CD 54）的表达以及白细胞介素-6和白细胞介素-8的分泌，但稳定的CAO-LMP 1表达未能引起这些作用。此外，B95.8-LMP 1，而不是CAO-LMP 1，诱导细胞形态的改变和变黑的上皮细胞分化。B95.8-LMP 1和CAO-LMP 1均诱导相似水平的核因子-κ B活化，但CAO-LMP 1活化AP-1通路的能力相对受损。这些数据突出了原型B95.8-LMP 1和CAO-LMP 1变体在人上皮细胞中稳定表达时的显著功能差异，并表明对LMP 1变体的持续分析将有助于进一步剖析LMP 1激活的信号通路，并提供对LMP 1序列变异对EBV相关肿瘤发病机制的贡献的见解。(C)北京大学出版社.
The contribution of Epstein-Barr Virus (EBV) strain Variation to the pathogenesis of virus-associated tumours remains unknown. Given the central role of LMP1 in EBV-induced transformation, much interest has focused on the influence of LMP1 sequence variation on the signaling pathways and multiple downstream phenotypic consequences of LMP1 expression. The identification of LMP1 variants with a common 10-amino-acid deletion and additional point mutations (typified by the CAO-LMP1 isolate) in EBV strains associated with nasopharyngeal carcinoma prompted us to examine the effect of stable prototype B95.8-LMP1 and CAO-LMP1 expression on the phenotype and differentiation of SCC12F human epithelial cells. Both forms of LMP1 were able to induce expression of the antiapoptotic A20 protein and provide protection from tumour necrosis factor-ct-induced cytotoxicity. Although B95.8-LMP1 induced growth inhibition, expression of certain cell surface molecules (CD40, CD44, and CD54), and secretion of interleukin-6 and -8 in SCC12F cells, stable CAO-LMP1 expression failed to elicit these effects. Furthermore, B95.8-LMP1, but not CAO-LMP1, induced alterations in cell morphology and blacked epithelial cell differentiation. Both B95.8-LMP1 and CAO-LMP1 induced similar levels of nuclear factor-kappa B activation, but the ability of CAO-LMP1 to activate the AP-1 pathway was relatively impaired. These data highlight significant functional differences between the prototype B95.8-LMP1 and the CAO-LMP1 variant when stably expressed in human epithelial cells and suggest that continued analysis of LMP1 variants will help to further dissect the signaling pathways activated by LMP1 as well as provide insights into the contribution of LMP1 sequence variation to the pathogenesis of EBV-associated tumours. (C) 2000 Academic Press.