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首页> 外文期刊>Oncology reports >The V-val subtype Epstein-Barr virus nuclear antigen 1 promotes cell survival after serum withdrawal
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The V-val subtype Epstein-Barr virus nuclear antigen 1 promotes cell survival after serum withdrawal

机译：V-val亚型爱泼斯坦-巴尔病毒核抗原1促进血清撤离后的细胞存活

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摘要

Epstein-Barr virus (EBV) can establish latent infection and has been associated with various human cancers. Epstein-Barr nuclear antigen 1 (EBNA1) is the only viral protein that is expressed in all EBV-associated malignant tissues. The N- and C-terminal domains of EBNA1, which are connected by internal glycine/alanine-rich short repeat sequences of various sizes, show sequence divergence across EBV strains isolated from around the world. At least five subtypes have been described, according to the amino acid at residue 487: P-ala, P-thr, V-val, V-pro, and V-leu. Whether the variations of EBNA-1 contribute to the pathogenesis of EBV or simply reflect the geographical distribution of EBV remain to be investigated. Furthermore, the cell effects conferred by EBNA1 subtypes that differ from that of the B95.8 prototype, which belongs to the P-ala subtype, remain to be elucidated. In this study, PCR was amplified with the full-length V-val EBNA1 gene from the CG3 cell line, an EBV-carrying lymphoblastoid cell line derived from a Taiwanese chronic myeloid leukemia patient. Plasmids expressing His-tagged EBNA1 fusion proteins in E. coli were constructed and used to raise antibodies in rabbit. The V-val EBNA1 gene was then cloned into a eukaryotic expression vector and successfully expressed in the transfected cultured cells. Expression of V-val EBNA1 rendered 293 cells able to undergo serum-independent cell proliferation, providing them with anti-apoptotic abilities, which are two characteristics of cancer cells. These data suggested that use of EBNA1 originally derived from tumor cells, rather than the more commonly utilized prototype, when investigating the potential role of EBNA1 in the oncogenesis of EBV-associated malignancies, is crucial.
机译：爱泼斯坦巴尔病毒（EBV）可以建立潜在的感染，并已与各种人类癌症有关。爱泼斯坦-巴尔核抗原1（EBNA1）是在所有与EBV相关的恶性组织中表达的唯一病毒蛋白。 EBNA1的N和C端结构域通过各种大小的内部富含甘氨酸/丙氨酸的短重复序列连接，它们在从世界各地分离的EBV病毒株之间显示出序列差异。根据残基487上的氨基酸，已经描述了至少五个亚型：P-ala，P-thr，V-val，V-pro和V-leu。 EBNA-1的变异是否有助于EBV的发病机理或仅反映EBV的地理分布仍有待研究。此外，由EBNA1亚型赋予的细胞效应与属于P-ala亚型的B95.8原型所赋予的细胞效应仍有待阐明。在这项研究中，PCR扩增了来自CG3细胞系的全长V-val EBNA1基因，该基因系来自台湾慢性髓性白血病患者的EBV携带淋巴母细胞样细胞系。构建在大肠杆菌中表达His标签的EBNA1融合蛋白的质粒，并用于在兔中产生抗体。然后将V-val EBNA1基因克隆到真核表达载体中，并在转染的培养细胞中成功表达。 V-val EBNA1的表达使293细胞能够进行不依赖血清的细胞增殖，使其具有抗凋亡能力，这是癌细胞的两个特征。这些数据表明，在调查EBNA1在与EBV相关的恶性肿瘤的肿瘤发生中的潜在作用时，使用最初源自肿瘤细胞的EBNA1至关重要，而不是更常用的原型。

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