Cell transformation by human adenoviruses.-猫眼课题宝

人腺病毒的细胞转化。

DOI：

10.1007/978-3-662-05599-1_6

发表时间：

2004

期刊：

Current topics in microbiology and immunology

影响因子：

通讯作者：

中科院分区：

医学3区

文献类型：

作者：

C. Endter;T. Dobner

过去40年来，对人类腺病毒的分子生物学研究极大地促进了我们对正常和恶性细胞生长基本原理的理解。这些知识大部分来自对它们在允许宿主细胞中的生产性感染周期的分析。此外，关于人类腺病毒致癌潜力的初步观察随后揭示了对癌症起源的分子机制的决定性见解，并建立了腺病毒作为解释病毒介导的转化过程的模型系统。目前已证实，人腺病毒的细胞转化是一个多步骤过程，涉及早期转录单位1A（E1A）和1B（E1B）中编码的几种基因产物。此外，大量的证据表明，替代或额外的机制参与腺病毒介导的致癌转化，涉及早期区域4（E4）编码的基因产物以及病毒DNA整合引起的表观遗传变化。特别是，对亚群D腺病毒9型（Ad9）E4的致瘤潜力的详细研究现在已经揭示了一种新的途径，指出了病毒介导的肿瘤发生的一种新的一般机制。在这一章中，我们总结了目前的知识状态的致癌基因和致癌基因产物的人腺病毒，特别是最近的研究结果，有关的转化和致癌特性的病毒蛋白编码的E1B和E4转录单位。

The last 40 years of molecular biological investigations into human adenoviruses have contributed enormously to our understanding of the basic principles of normal and malignant cell growth. Much of this knowledge stems from analyses of their productive infection cycle in permissive host cells. Also, initial observations concerning the carcinogenic potential of human adenoviruses subsequently revealed decisive insights into the molecular mechanisms of the origins of cancer, and established adenoviruses as a model system for explaining virus-mediated transformation processes. Today it is well established that cell transformation by human adenoviruses is a multistep process involving several gene products encoded in early transcription units 1A (E1A) and 1B (E1B). Moreover, a large body of evidence now indicates that alternative or additional mechanisms are engaged in adenovirus-mediated oncogenic transformation involving gene products encoded in early region 4 (E4) as well as epigenetic changes resulting from viral DNA integration. In particular, detailed studies on the tumorigenic potential of subgroup D adenovirus type 9 (Ad9) E4 have now revealed a new pathway that points to a novel, general mechanism of virus-mediated oncogenesis. In this chapter, we summarize the current state of knowledge about the oncogenes and oncogene products of human adenoviruses, focusing particularly on recent findings concerning the transforming and oncogenic properties of viral proteins encoded in the E1B and E4 transcription units.