GENETIC STRUCTURE OF MURINE RETROVIRUSES

鼠逆转录病毒的遗传结构

• 批准号: 6160575
• 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/6160575
• 关键词: gene induction /repression; laboratory mouse; murine leukemia virus; neoplasm /cancer genetics; protooncogene; viral carcinogenesis; viral leukemia; virus genetics

The major focus of this project has been on the genetic alteration of retroviruses as a result of recombination and point mutations. Such alterations generate mixed retroviral infections which are a hallmark of all in vivo retroviral infections. These include HIV and HTLV infections, which give rise to AIDS and T-cell leukemia in humans, and murine retrovirus infections which frequently result in proliferative, immunological or neurological diseases in mice. Our recent studies have investigated the effects of mixed in vivo retroviral infections after co-inoculation of mice with mixtures of murine leukemia viruses (MuLV). Infection by ecotropic MuLVs generally results in the de novo generation of polytropic MuLVs, which are recombinants between the inoculated ecotropic MuLV and endogenous polytropic MuLV envelope genes present in the genomes of inbred mice. The recombinant polytropic MuLVs, which have been implicated in pathogenicity, utilize a distinct cell-surface receptor and exhibit an infectious host range which differs from ecotropic MuLVs. We have found that infection of mice with mixtures of a polytropic MuLV and an ecotropic MuLV results in nearly complete suppression of de novo generation of polytropic MuLVs. Our results indicate that both viruses initially infect the same small population of cells of the monocyte/macrophage lineage and suggest that in vivo interference at this stage of infection may preclude further infectious spread of viruses. Further studies will determine if the small cell population is the initial target for other types of retroviruses and investigate if infection of this cell is a prerequisite for efficient infection of the mouse.

这个项目的主要关注点是基因改变。 逆转录病毒是重组和点突变的结果。是这样的 基因改变会产生混合逆转录病毒感染，这是一个标志 在所有体内逆转录病毒感染中。这些病毒包括HIV和HTLV 感染，这会导致人类艾滋病和T细胞白血病，以及 小鼠逆转录病毒感染，经常导致增殖性， 小鼠的免疫性或神经系统疾病。我们最近的研究表明 研究了体内混合逆转录病毒感染后的影响 小鼠与小鼠白血病病毒(MuLV)混合接种。 由生态型MuLV感染通常会导致新生 多变性MULV的产生，它们是 接种生态型和内源性多向型小轮状病毒囊膜基因 存在于近亲交配的小鼠的基因组中。重组多效性 已被认为与致病性有关的MULV利用一种独特的 细胞表面受体，并表现出不同的感染宿主范围 来自生态型MuLV。我们已经发现，用混合物感染小鼠 多变MuLV和生态MuLV的结果是几乎完全的 抑制多变MULV的从头产生。我们的结果 表明这两种病毒最初感染的是同一小部分人群 单核/巨噬细胞谱系的细胞，并提示在体内 在感染的这个阶段进行干预可能会阻止进一步的传染性 病毒的传播。进一步的研究将确定小细胞是否 种群是其他类型逆转录病毒的初始目标， 调查这种细胞的感染是否是有效的先决条件 老鼠的感染。