GENETIC STRUCTURE OF MURINE RETROVIRUSES

鼠逆转录病毒的遗传结构

• 批准号: 3818163
• 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/3818163
• 关键词: Retroviridae disease; gene expression; genetic recombination; laboratory mouse; monoclonal antibody; mouse leukemia; murine leukemia virus; nucleic acid sequence; oncogenic virus; tissue /cell culture; virus classification; virus envelope; virus genetics; virus infection mechanism; virus protein; virus replication

The effects of genetic alterations of retroviruses include the generation of variant viruses which infect different hosts; viruses which are capable of infecting different tissues in the host; and virus variants which exhibit enhanced pathogenicity compared to the "wild type" virus. Such alterations have been documented with nearly all groups of retroviruses, including avian, murine, equine, and most recently with HIV, the etiological agent of AIDS. This project is largely focused on the genetic alteration of murine leukemia viruses (MuLVs), principally with regard to alterations due to recombination and the role of this process in disease induction. Previous studies include the identification of a novel recombinant virus which provided a detailed model for the generation of oncogenic viruses in mice which exhibit a high incidence of leukemia. In our current studies we have demonstrated the generation of a variant virus in cell culture by spontaneous recombination between viruses postulated as intermediates in our model. The variant virus exhibits in vitro properties indistinguishable from those of oncogenic recombinant viruses isolated from mice, and is currently being tested for in vivo oncogenicity. Other studies have demonstrated that the viral envelope protein strongly influences the tissue in which viruses replicate at early times alter inoculation, whereas viral sequences which control the rate of transcription influence tissue-specific expression at later times. These results have been extended to show that early pathological events in leukemia induction are influenced by the viral envelope protein, while the type of leukemia which subsequently develops at later times is influenced by transcriptional control elements. Many of these studies have been greatly facilitated by the development of a retrovirus assay on live cells using monoclonal antibodies. To further extend the usefulness of this assay we have developed a broadly reactive monoclonal antibody directed at the envelope proteins of MuLVs. The antibody facilitates the assay of a very broad spectrum of MuLVs, including the amphotropic MuLVs for which no monoclonal antibodies directed at the envelope protein have been described.

逆转录病毒基因改变的影响包括 变种病毒感染不同宿主的变异病毒的产生；病毒 它们能够感染宿主的不同组织；以及 与病毒变种相比，病毒变种表现出更强的致病性 野生型病毒。这样的改变已经被记录在 几乎所有的逆转录病毒组，包括禽类、小鼠、马类、 最近还感染了艾滋病毒，这是艾滋病的病原体。这 该项目主要集中在小鼠的基因改变上 白血病病毒(MuLV)，主要与改变有关 由于重组和这一过程在疾病中的作用 归纳法。以前的研究包括对小说的鉴定 重组病毒提供了一个详细的模型 在小鼠体内产生高致癌病毒 白血病的发病率。在我们目前的研究中，我们已经证明 在细胞培养中自发产生一种变异病毒 在我们的研究中假设为中间体的病毒之间的重组 模特。变种病毒在体外表现出特性 与致癌重组病毒没有区别 从小鼠身上分离出来，目前正在进行体内测试 致癌性。其他研究表明，这种病毒 包膜蛋白强烈影响病毒所在的组织 在接种后的早期复制，而病毒序列 它们控制着影响组织特异性转录的速度 在以后的时间表达。这些结果已推广到 研究表明，诱导白血病的早期病理事件包括 受病毒包膜蛋白的影响，而类型 随后发展成的白血病会受到影响。 通过转录调控元件。许多这样的研究都有 极大地促进了逆转录病毒检测的发展 在活细胞上使用单抗。为了进一步扩展 这种分析的实用性我们已经开发出一种广泛的反应性 针对MULV包膜蛋白的单抗。 该抗体有助于测定非常广泛的 MULV，包括没有克隆的两性MULV 已经描述了针对包膜蛋白的抗体。