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潜伏性爱泼斯坦-巴尔病毒感染的生物化学及相关细胞生长转化

Biochemistry of latent Epstein-Barr virus infection and associated cell growth transformation.

作者信息

Kieff E, Hennessy K, Fennewald S, Matsuo T, Dambaugh T, Heller M, Hummel M

出版信息

IARC Sci Publ. 1985(60):323-39.

PMID:2998995
Abstract

There is sufficient knowledge of the biochemistry of Epstein-Barr virus (EBV) persistence and gene expression in latent growth-transforming infection and of the persistence and expression of other oncogenic viruses to permit interesting and possibly useful comparisons. Most smaller oncogenic viral genomes usually persist solely as integrated DNAs despite their ability to circularize. Papilloma and hepatitis viruses may persist as episomes, and parts of their genomes may integrate. Usually, only the oncogenic fragment of adenovirus DNA is integrated into cell DNA. In contrast, the entire EBV genome persists in cells as an episome or as integrated DNA. Thus, EBV may have novel mechanisms to maintain its complete genome as an episome or as a complete integrated virus DNA. Three viral genes are expressed in latently EBV-infected growth-transformed cells, each of which encodes one RNA and one protein. Two of the proteins are probably nuclear DNA-binding proteins; the third is probably a membrane protein. Thus, the repertoire of genes expressed is similar in complexity and intracellular distribution to that expressed by papova and adenoviruses in cellular transformation. The papova and adenovirus-transforming genes are partially analogous to retrovirus oncogenes. This similarity cannot as yet be extended to EBV. There is no homology at the DNA-sequence or protein-sequence level between EBV and other viral or cell oncogenes. Thus, it remains important to pursue analysis of the EBV-transforming genes. Identification of these genes is a first step in discerning their function in latent growth-transforming cell infection. Parts of each of these genes are being made in bacteria. The bacterial products enable us to make antisera that are specific for each of the viral proteins. These antisera can also be used to identify the viral proteins within latently infected growth-transformed cells or within cells stably expressing transfected virus genes. The antisera can also be used to study the association of Epstein-Barr nuclear antigen (EBNA) 1 and 2 with DNA and of the lymphocyte-determined membrane antigen (LYDMA) with the cell membrane. The three genes must be introduced into nontransformed cells to determine whether, alone or in combination, they are sufficient to accomplish cell growth transformation.

摘要

对于爱泼斯坦 - 巴尔病毒(EBV)在潜伏性生长转化感染中的持续存在和基因表达的生物化学,以及其他致癌病毒的持续存在和表达,已有足够的了解,从而可以进行有趣且可能有用的比较。大多数较小的致癌病毒基因组尽管能够环化,但通常仅以整合DNA的形式持续存在。乳头瘤病毒和肝炎病毒可能以附加体的形式持续存在,其基因组的部分片段可能会整合。通常,只有腺病毒DNA的致癌片段会整合到细胞DNA中。相比之下,EBV的整个基因组以附加体或整合DNA的形式存在于细胞中。因此,EBV可能具有将其完整基因组维持为附加体或完整整合病毒DNA的新机制。在潜伏感染EBV的生长转化细胞中表达三种病毒基因,每种基因编码一种RNA和一种蛋白质。其中两种蛋白质可能是核DNA结合蛋白;第三种可能是膜蛋白。因此,所表达基因的种类在复杂性和细胞内分布上与多瘤病毒和腺病毒在细胞转化中所表达的相似。多瘤病毒和腺病毒的转化基因部分类似于逆转录病毒癌基因。这种相似性目前还不能扩展到EBV。EBV与其他病毒或细胞癌基因在DNA序列或蛋白质序列水平上没有同源性。因此,继续分析EBV转化基因仍然很重要。鉴定这些基因是识别它们在潜伏性生长转化细胞感染中功能的第一步。这些基因的每个部分都正在细菌中制备。细菌产物使我们能够制备针对每种病毒蛋白的抗血清。这些抗血清还可用于鉴定潜伏感染的生长转化细胞内或稳定表达转染病毒基因的细胞内的病毒蛋白。这些抗血清还可用于研究爱泼斯坦 - 巴尔核抗原(EBNA)1和2与DNA的关联以及淋巴细胞决定的膜抗原(LYDMA)与细胞膜的关联。必须将这三种基因导入未转化的细胞中,以确定它们单独或组合起来是否足以完成细胞生长转化。

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An Epstein-Barr virus isolated from a lymphoblastoid cell line has a 16-kilobase-pair deletion which includes gp350 and the Epstein-Barr virus nuclear antigen 3A.从一个淋巴母细胞系分离出的爱泼斯坦-巴尔病毒有一个16千碱基对的缺失,其中包括gp350和爱泼斯坦-巴尔病毒核抗原3A。
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A bicistronic Epstein-Barr virus mRNA encodes two nuclear proteins in latently infected, growth-transformed lymphocytes.一个双顺反子的爱泼斯坦-巴尔病毒信使核糖核酸在潜伏感染、生长转化的淋巴细胞中编码两种核蛋白。
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