Genetic Analysis of EBV's Immortalizing Genes

EB病毒（EBV）是一种肿瘤病毒，可导致淋巴瘤和癌， 每年10万人。我们已经开发并应用了EB病毒转化基因的遗传分析， 该基金的优先支持集中在感染的B中EBV的潜伏膜蛋白1（LMP 1）- 淋巴细胞这些分析鉴定了LMPV快速诱导的表型和细胞基因 发信号。我们建议扩展我们的遗传分析，进一步剖析LMP 1的转化功能， EB病毒核抗原1（EBNA 1）和EBV的microRNA（miRNAs），通过鉴定表型， 诱导和它们调节细胞基因。这些病毒转化基因都与维持 在某些或全部EBV相关肿瘤中的肿瘤表型。我们提出的基因分析将有助于 阐明这些病毒转化基因如何促进肿瘤维持。我们也将扩大 对这些病毒基因进行遗传分析，以剖析它们在受感染的上皮细胞中的功能。EB病毒导致更多 癌比淋巴瘤，但研究正常上皮细胞以前是棘手的。这些细胞 现在可以感染，使我们能够描述EB病毒的转化基因。EB V功能 在B淋巴细胞和上皮细胞中的差异。我们假设这些病毒转化基因调节 不同的细胞基因在B淋巴细胞和上皮细胞介导EBV的不同致癌 捐款. 对EB病毒转化基因的遗传分析将有助于确定它们对EB病毒感染的贡献。 维持EBV相关的淋巴瘤和癌。了解病毒对肿瘤的作用 维持将允许开发特异性抗病毒、抗肿瘤疗法。

Epstein-Barr Virus (EBV) is a tumor virus that causes lymphdmas and carcinomas in approximately 100,000 people each year. We have developed and applied genetic analyses of EBV's transforming genes with this grant's prior support focusing on EBV's latent membrane protein 1 (LMP1) in infected B- lymphocytes. These analyses identified a phenotype and cellular genes induced rapidly by LMPVs signaling. We propose to extend our genetic analysis to dissect further transforming functions of LMP1, Epstein-Barr Nuclear Antigen 1 (EBNA1), and EBV's microRNAs (miRNAs) by identifying phenotypes they induce and cellular genes they regulate. These viral transforming genes are all implicated in maintaining tumor phenotypes in some or all of EBV-associated tumors. Our proposed genetic analyses will help to elucidate how these viral transforming genes contribute to tumor maintenance. We shall also extend our genetic analyses of these viral genes to dissect their functions in infected epithelial cells. EBV causes more carcinomas than lymphomas, but studies in normal epithelial cells formerly were intractable. These cells are now amenable to infection allowing us to characterize EBV's transforming genes in them. EBV functions differently in B-lymphocytes and epithelial cells. We hypothesize that these viral transforming genes regulate different cellular genes in B-lymphocytes and epithelial cells to mediate EBV's different oncogenic contributions. The proposed genetic analysis of EBV's transforming genes will help to identify their^contributionsto maintaining EBV-associated lymphomas and carcinomas. An understanding of viral contributions to tumor maintenance will allow development of specific anti-viral, anti-tumor therapies.