Widespread sequence variation in the Epstein-Barr virus latent membrane protein 2A gene among northern Chinese isolates.
Widespread sequence variation in the Epstein-Barr virus latent membrane protein 2A gene among northern Chinese isolates.
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DOI：
10.1099/vir.0.021881-0
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发表时间：
2010-10
期刊：
影响因子：
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通讯作者：
xingang wang;Xia Liu;Yu-ping Jia;Yan Chao;X. Xing;Yun Wang;B. Luo
中科院分区：
文献类型：
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作者：
xingang wang;Xia Liu;Yu-ping Jia;Yan Chao;X. Xing;Yun Wang;B. Luo
潜伏膜蛋白2A（LMP 2A）在大多数EB病毒（EBV）相关的恶性肿瘤中表达。除了其在维持潜伏感染和上皮细胞转化中的作用外，LMP 2A还可以作为EBV相关恶性肿瘤的基于CTL的治疗的靶点。本研究对中国北方EB病毒相关胃癌患者、鼻咽癌患者和健康献血员的LMP 2A序列多态性进行了鉴定，并与原型B 95 -8株进行了比较。在所有分离株中检测到四种一致的突变。在分析的序列中的频繁突变区分两种和七种类型的外显子1和外显子2-8的序列变异，分别与两个基因片段的基因分型之间没有一致的关联。氨基端的免疫受体酪氨酸激活基序和PY基序是严格保守的。16个鉴定的CTL表位中有9个受到至少一个点突变的影响，这可能会使针对EBV相关恶性肿瘤的免疫治疗方法变得复杂。大多数改变的表位在肿瘤分离株中的突变率高于健康供体的洗喉样本，这与病毒株可以通过改变LMP表位内的氨基酸来逃避免疫监视的想法一致。LMP 2A基因序列变异的首次详细研究揭示了外显子1和外显子2-8中可分类的序列多态性，并鼓励进一步研究病毒基因变异对肿瘤持久性和基于CTL的免疫治疗的影响。
Latent membrane protein 2A (LMP2A) is expressed in most Epstein-Barr virus (EBV)-associated malignancies. Besides its roles in the maintenance of latent infection and epithelial-cell transformation, LMP2A could also act as the target for a CTL-based therapy for EBV-associated malignancies. In the present study, sequence polymorphisms in LMP2A from northern Chinese EBV-associated gastric carcinoma patients, nasopharyngeal carcinoma patients and healthy donors were identified and compared with the prototype B95-8 strain. Four consistent mutations were detected in all isolates. Frequent mutations in the analysed sequences distinguished two and seven types of sequence variation in exon 1 and exons 2-8, respectively, with no consistent association shown between the genotyping of the two gene fragments. The immunoreceptor tyrosine-based activation motif and PY motif in the amino terminus were strictly conserved. Nine of the 16 identified CTL epitopes were affected by at least one point mutation, which may confer complexity to proposed immunotherapeutic approaches for EBV-associated malignancies. Most changed epitopes showed higher mutation rates in tumour isolates than in throat-washing samples from healthy donors, in accordance with the idea that virus strains can evade immune surveillance by altering amino acids within LMP epitopes. This first detailed investigation of sequence variations in the LMP2A gene reveals classifiable sequence polymorphisms in exon 1 and exons 2-8, and encourages further work on the impact of viral gene variations on tumour persistence and CTL-based immunotherapy.