Tanaka M, Kawaguchi Y, Yokofujita J, Takagi M, Eishi Y, Hirai K
Department of Tumor Virology, Medical Research Institute, Tokyo Medical and Dental University, Yushima, Tokyo, Japan.
Virus Genes. 1999;19(2):103-11. doi: 10.1023/a:1008171006400.
The latent EBV gene products expressed in Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC), are only LMP2A, EBNA-1, BARF-0 and EBERs. To examine the correlation between LMP2A sequence variation in EBVaGC and transformation of the cells, the complete sequence of the LMP2A gene was determined in three cases of Japanese EBVaGC and compared with the prototype B95-8 strain. In addition, the sequences of exons 2,6 and 7 of LMP2A were determined in four to six EBVaGC cases. The results of sequence analysis indicated that LMP2A of EBVaGC was structurally very similar to B95-8, but contained a significant nucleotide variation. Ten nucleotide substitutions were identified in almost all cases tested, and three of these caused amino acid changes. Of these three, two amino acid substitutions were not expected to change any known functions of LMP2A. The other amino acid substitution from serine to threonine was located at codon 348 within one of the target epitopes of EBV-specific cytotoxic T-lymphocytes. The LMP2A of EBV in peripheral blood lymphocytes from six healthy individuals showed serine (4/6 cases) or threonine (2/6 cases) substitution at codon 348, while LMP2A with the threonine substitution was the major form (5/6 cases) observed in EBVaGC, indicating that EBV with the threonine substitution may confer an advantage for viral persistence in tumor cells. However, our sequencing results suggested that the LMP2A protein in EBVaGC is functionally similar to that of the B95-8 strain and is not unique to gastric carcinoma, indicating the importance of LMP2A for EBV latency.
在与爱泼斯坦 - 巴尔病毒（EBV）相关的胃癌（EBVaGC）中表达的潜伏性EBV基因产物只有LMP2A、EBNA - 1、BARF - 0和EBERs。为了研究EBVaGC中LMP2A序列变异与细胞转化之间的相关性，测定了3例日本EBVaGC中LMP2A基因的完整序列，并与原型B95 - 8株进行比较。此外，还测定了4至6例EBVaGC中LMP2A外显子2、6和7的序列。序列分析结果表明，EBVaGC的LMP2A在结构上与B95 - 8非常相似，但存在显著的核苷酸变异。在几乎所有测试病例中都鉴定出10个核苷酸替换，其中3个导致氨基酸改变。在这3个氨基酸替换中，有2个预计不会改变LMP2A的任何已知功能。另一个从丝氨酸到苏氨酸的氨基酸替换位于EBV特异性细胞毒性T淋巴细胞的一个靶表位内的密码子348处。6名健康个体外周血淋巴细胞中EBV的LMP2A在密码子348处显示丝氨酸（4/6例）或苏氨酸（2/6例）替换，而在EBVaGC中观察到的主要形式是苏氨酸替换的LMP2A（5/6例），这表明具有苏氨酸替换的EBV可能在肿瘤细胞中具有病毒持续存在的优势。然而，我们的测序结果表明，EBVaGC中的LMP2A蛋白在功能上与B95 - 8株相似，并非胃癌所特有，这表明LMP2A对EBV潜伏的重要性。
