Tabata YHibi S, Teramura T, Kuriyama K, Yagi T, Todo S, Sawada T, Imashuku S
Department of Pediatrics, Kyoto Prefectural University of Medicine, Japan.
Leuk Lymphoma. 2000 Jul;38(3-4):373-80. doi: 10.3109/10428190009087028.
Latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is considered to be an oncoprotein because it is crucial for B-lymphocyte transformation. Since a 30 base pair (bp) deletion in the carboxy-terminal portion of the LMP1 gene was found in a CAO cell line derived from nasopharyngeal carcinoma containing EBV, an association between EB viral genetic alteration and tumorigenicity has been postulated. In this study we have analyzed LMP1 DNA isolated from 10 Japanese patients with EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). In all HLH patients, we found the 30 bp deletion and 4-8-tandem repeats of the sequence DNGPQDPDNTD in the LMP1 gene. Furthermore, detailed amino acid (aa) sequence analysis revealed that 7 aa substitutions identical to those found in CAO-LMP1 but not in B95.8 cell line-LMP1 were found in all the HLH cases. NF-kappaB assay revealed that HLH-LMP1 activated NF-kappaB significantly more than that of B95.8-LMP1 (p=0.032). We conclude that EBV from all of our HLH cases shared common genetic characteristics with EBV obtained from the CAO cell line, which is distinct from the wild-type EBV isolated from the B95.8 cell line. These data suggest that the mutational changes of the LMP1 gene may play an important role in the pathogenesis of these fatal EBV-related disorders.
爱泼斯坦-巴尔病毒（EBV）的潜伏膜蛋白1（LMP1）被认为是一种癌蛋白，因为它对B淋巴细胞转化至关重要。由于在一株源自含EBV的鼻咽癌的CAO细胞系中发现LMP1基因的羧基末端部分有一个30碱基对（bp）的缺失，因此推测EB病毒基因改变与致瘤性之间存在关联。在本研究中，我们分析了从10例日本EBV相关噬血细胞性淋巴组织细胞增生症（EBV-HLH）患者中分离出的LMP1 DNA。在所有HLH患者中，我们在LMP1基因中发现了30 bp的缺失以及序列DNGPQDPDNTD的4-8个串联重复。此外，详细的氨基酸（aa）序列分析显示，在所有HLH病例中均发现了7个氨基酸替换，这些替换与CAO-LMP1中发现的相同，但在B95.8细胞系-LMP1中未发现。NF-κB检测显示，HLH-LMP1比B95.8-LMP1更显著地激活NF-κB（p = 0.032）。我们得出结论，我们所有HLH病例中的EBV与从CAO细胞系获得的EBV具有共同的遗传特征，这与从B95.8细胞系分离出的野生型EBV不同。这些数据表明，LMP1基因的突变变化可能在这些致命的EBV相关疾病的发病机制中起重要作用。
