RETROVIRUS REGULATION IN VITRO AND DURING DEVELOPMENT

逆转录病毒的一个有充分证据的特征是大多数病毒分离株， 尽管能够在感染的各种组织中复制 动物只在一种或一小部分细胞类型中诱发肿瘤。为 非急性转化性禽类和鼠类逆转录病毒，根据定义 不含病毒相关癌基因，肿瘤的特异性 诱因以及病毒致病的频率， 主要用包含 病毒增强剂和促进剂。在此应用程序中建议进行实验 用禽类非急性转化病毒研究鸡瘟病毒的特性 定义(A)频率和(B)特异性的不同病毒LTRs 肿瘤诱导和(C)干扰表达的机制(S) 肿瘤中前病毒整合部位的细胞基因。这些地区 通过定义野生型的转录特性进行研究， 来自高致癌和弱致癌病毒的突变体和重组LTRs 通过体内复制能力病毒的致瘤性测试 包括这些LTR。还包括实验来描述一部小说的特征 禽类逆转录病毒中定义的公共整合位点(BRAVO) 诱导B细胞淋巴瘤并确定前病毒的作用 在这个轨迹上的整合。本应用程序中的研究将有助于 我们对所涉及的病毒成分的识别和调控的理解 在肿瘤诱导中的作用以及细胞转录因子和 细胞癌基因也在这一过程中发挥作用。此外，建议的 对Bravo基因的研究可能会在 鉴于许多以前被描述为普通前病毒的 肿瘤中的整合位点识别有助于正常 细胞的生长、分化或发育，以其异常的形式， 到细胞转化。

A well documented feature of retroviruses is that most virus isolates, although able to replicate in a wide variety of tissues in infected animals, induce tumors in only one or a small number of cell types. For non-acute transforming avian and murine retroviruses, which by definition do not contain viral-associated oncogenes, the specificity of tumor induction as well as the frequency with which a virus causes disease, segregate primarily with the long terminal repeat (LTR) that contains the viral enhancer and promoter. Experiments are proposed in this application to use avian non-acute transforming viruses to investigate properties of different viral LTRs that define (a) the frequency and (b) the specificity of tumor induction and (c) the mechanism(s) employed to disrupt expression of cellular genes at sites of provirus integration in tumors. These areas are investigated by defining the transcriptional properties of wild type, mutant, and recombinant LTRs from highly and weakly oncogenic viruses and by in vivo oncogenicity testing of replication competent viruses that include these LTRs. Experiments are also included to characterize a novel common integration site (bravo) that has been defined in avian retrovirus induced B cell lymphomas and to determine the effects of provirus integration at this locus. Studies in this application will contribute to our understanding of the identity and regulation of viral elements involved in tumor induction and of the role that cellular transcription factors and cellular oncogenes play in this process as well. In addition, the proposed studies on the bravo locus are likely to yield important information in light of the fact that many of the previously characterized common provirus integration sites in tumors identify genes that contribute to both normal cell growth, differentiation or development and, in their abnormal form, to cellular transformation.