Genetic Analysis of EBV's Immortalizing Genes

爱泼斯坦-巴尔病毒(Epstein-Barr Virus，EBV)是一种肿瘤病毒，可导致大约 每年有10万人。我们已经开发并应用了EBV转化基因的遗传分析 由于这笔赠款之前的支持重点是EB病毒在感染的B-杆菌中的潜伏膜蛋白1(LMP1)。 淋巴细胞。这些分析确定了LMPV快速诱导的表型和细胞基因。 发信号。我们建议将我们的遗传分析扩展到进一步剖析LMP1的转化功能， Epstein-Barr核抗原1(EBNA1)和EBV的microRNAs(MiRNAs) 诱导和它们调节的细胞基因。这些病毒转化基因都与维持 部分或全部EBV相关肿瘤的肿瘤表型。我们建议的基因分析将有助于 阐明这些病毒转化基因如何对肿瘤的维持起作用。我们还将延长我们的 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。EBV导致更多 癌症比淋巴瘤好，但以前对正常上皮细胞的研究很难解决。这些细胞是 现在易受感染，使我们能够表征EBV在其中的转化基因。EBV函数 在B淋巴细胞和上皮细胞中不同。我们假设这些病毒转化基因调节 B淋巴细胞和上皮细胞中不同细胞基因介导EB病毒不同致癌作用 贡献。 拟议的EBV转化基因的遗传分析将有助于确定它们对 维持EBV相关的淋巴瘤和癌症。对病毒对肿瘤的贡献的认识 维护将允许开发特定的抗病毒、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.