GENETIC STRUCTURE OF MURINE RETROVIRUSES

鼠逆转录病毒的遗传结构

• 批准号: 3822019
• 负责人: L H EVANS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3822019
• 关键词: Friend virus; Retroviridae disease; gene expression; gene mutation; genetic recombination; genetic strain; immunofluorescence technique; monoclonal antibody; mouse leukemia; murine leukemia virus; mutant; nucleic acid sequence; oncogenic virus; point mutation; provirus; tissue /cell culture; virus RNA; virus antigen; virus classification; virus cytopathogenic effect; virus envelope; virus genetics; virus infection mechanism; virus morphology; virus replication

Genetic alterations of retgroviruses have been documented with lentiviruses such as EIAV and the AIDS virus, as well as with murine leukemia viruses (MuLVs). Ecotropic MuLVs undergo recombination with gene sequences of the mouse to generate recombinant viruses termed polytropic or mink cell focus-forming (MCF) viruses, which have frequently been implicated as the proximal agents involved in transformation to malignancy. A major goal of this project is to characterize the recombinant MuLVs and to define their role in disease induction. Initial studies demonstrated that ecotropic viruses which induce distinct types of leukemias (i.e., erythroleukemia vs. lymphocytic leukemia) recombine with distinct mouse genes to generate MCF viruses. We have extended these studies using a novel retrovirus assay to define new major populations of recombinant viruses which were undetected using conventional assays. The new recombinants isolated during erythroleukemia induction exhibited distinctly different infectious properties than those isolated during lymphocytic leukemia induction and, in both cases, represented the overwhelming majority of recombinant viruses present. Additional studies on tissue-specific replication of ecotropic viruses indicated that the site of replication is controlled by multiple sequences of the viruses, and that leukemia induction requires a high level of replication in the oncogenic target tissue only transiently, early after infection. AKR mice exhibit a high level of spontaneous leukemia and express oncogenic recombinant viruses immediately preceding the earliest incidence of leukemia. The recombinants generated in AKR mice are derived by a stepwise recombination mechanism which is not fully understood. We have identified and studied the structure and expression of a new virus in AKR mice which appears to serve as a recombination intermediate in this stepwise process. Our findings have enabled us to arrive at a detailed model for the generation of the oncogenic recombinants.

逆转录病毒的基因改变已被记录 慢病毒，例如 EIAV 和 AIDS 病毒，以及 鼠白血病病毒（MuLV）。 生态性 MuLV 经历 与小鼠基因序列重组生成 称为多向性或水貂细胞病灶形成的重组病毒 (MCF) 病毒，经常被认为是 参与恶性肿瘤转化的近端因子。 一个 该项目的主要目标是表征重组 MuLV 并定义它们在疾病诱导中的作用。 初步研究 证明亲食性病毒可诱导不同类型 白血病（即红白血病与淋巴细胞白血病） 与不同的小鼠基因重组产生 MCF 病毒。 我们使用新型逆转录病毒测定法扩展了这些研究 定义了重组病毒的新主要种群 使用常规检测无法检测到。 新的重组体 在红白血病诱导过程中分离的菌株表现出明显的 与隔离期间隔离的感染特性不同 淋巴细胞白血病诱导，并且在这两种情况下都代表 存在绝大多数重组病毒。 关于亲食性组织特异性复制的其他研究 病毒表明复制位点是由 病毒的多个序列，以及白血病诱导 需要在致癌靶组织中进行高水平的复制 只是短暂的，感染后早期。 AKR 小鼠表现出高水平的自发性白血病 表达致癌重组病毒之前 白血病发病最早。 产生的重组体 AKR小鼠是通过逐步重组机制衍生的 这还没有完全理解。 我们已经确定并研究了 一种新病毒的结构和在 AKR 小鼠中的表达 似乎在此逐步过程中充当重组中间体 过程。 我们的发现使我们能够得出详细的 产生致癌重组体的模型。