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中国霍奇金淋巴瘤患者和健康供体中爱泼斯坦-巴尔病毒基因多态性:三种不同病毒变体的鉴定

Epstein--Barr virus gene polymorphisms in Chinese Hodgkin's disease cases and healthy donors: identification of three distinct virus variants.

作者信息

Zhou X-G, Sandvej K, Li P-J, Ji X-L, Yan Q-H, Zhang X-P, Da J-P, Hamilton-Dutoit S J

机构信息

Departments of Pathology of Beijing Hospital3, Beijing Children's Hospital4, Beijing 301 Hospital5, Beijing Railway General Hospital6, Wunancabumong District Hospital7 and Beijing Air Army General Hospital8, People's Republic of China.

Research Unit of Molecular Medicine, Aarhus University Hospital and Faculty of Health Sciences, Aarhus, Denmark2.

出版信息

J Gen Virol. 2001 May;82(Pt 5):1157-1167. doi: 10.1099/0022-1317-82-5-1157.

DOI:10.1099/0022-1317-82-5-1157
PMID:11297690
Abstract

Epstein--Barr virus (EBV) is associated with several malignancies. Specific EBV gene variants, e.g. the BamHI f configuration, a C-terminal region 30 bp deletion in the latent membrane protein-1 (LMP1) gene (del-LMP) and the loss of an XhoI site in LMP1 (XhoI-loss), are found in Chinese cases of nasopharyngeal carcinoma (NPC), suggesting that EBV sequence variation may be involved in oncogenesis. In order to understand better the epidemiology of these EBV variants, they were studied in virus isolates from EBV-positive Chinese cases of Hodgkin's disease (HD; n=71) and donor throat washings from healthy CHINESE: Sequencing was performed of 15 representative EBV isolates, including the first analysis of the LMP1 promoter in Asian wild-type EBV isolates. The following observations were made. (i) Three EBV LMP1 variants were identified, designated Chinese groups (CG) 1--3. In both EBV-associated HD and in healthy Chinese, CG1-like viruses showing del-LMP1 and XhoI-loss were predominant. (ii) CG1viruses were distinct from European and African variants, suggesting that this profile is useful for epidemiological studies. (iii) Specific patterns of mutations were present in the LMP1 promoter in both CG1 and CG2. (iv) The BamHI f variant was not found in Chinese HD, in contrast to Chinese NPC and European HD. This study confirms that EBV isolates in Chinese HD and other tumours differ from those reported in Western cases. However, this reflects the predominant virus strain present in the healthy Chinese population, suggesting that these are geographically restricted polymorphisms rather than tumour-specific strains.

摘要

爱泼斯坦-巴尔病毒(EBV)与多种恶性肿瘤相关。在中国鼻咽癌(NPC)病例中发现了特定的EBV基因变异,例如BamHI f构型、潜伏膜蛋白-1(LMP1)基因C端区域30bp缺失(del-LMP)以及LMP1中XhoI位点缺失(XhoI-loss),这表明EBV序列变异可能参与肿瘤发生。为了更好地了解这些EBV变异的流行病学情况,对来自EBV阳性中国霍奇金淋巴瘤(HD;n = 71)病例的病毒分离株以及健康中国人的供体咽喉冲洗液进行了研究:对15株具有代表性的EBV分离株进行了测序,包括对亚洲野生型EBV分离株中LMP1启动子的首次分析。得出了以下观察结果。(i)鉴定出三种EBV LMP1变异体,命名为中国组(CG)1 - 3。在EBV相关的HD和健康中国人中,显示del-LMP1和XhoI-loss的CG1样病毒占主导。(ii)CG1病毒与欧洲和非洲变异体不同,表明这种特征对流行病学研究有用。(iii)CG1和CG2的LMP1启动子中均存在特定的突变模式。(iv)与中国NPC和欧洲HD不同,在中国HD中未发现BamHI f变异体。这项研究证实,中国HD和其他肿瘤中的EBV分离株与西方病例中报道的不同。然而,这反映了健康中国人群中存在的主要病毒株,表明这些是地理上受限的多态性而非肿瘤特异性菌株。

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