GENETIC STRUCTURE OF MURINE RETROVIRUSES

鼠逆转录病毒的遗传结构

• 批准号: 3960511
• 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/3960511
• 关键词: Friend virus; 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

Retroviruses commonly undergo genetic alterations. These include point mutations, which have been documented with the lenti viruses such as visna, EIAV and the AIDS virus, as well as major substitutions with host genes which have been documented with murine leukemia viruses (MuLVs). Ecotropic MuLVs (MuLVs which infect only murine cells) undergo recombination with endogenous sequences of the mouse to generate polytropic viruses (MuLVs which infect cells of other species). The major goal of this project is to characterize recombinant MuLVs generated between ecotropic MuLVs and gene sequences of the mouse, and to define their role in the disease process. Initial studies demonstrated that polytropic MuLVs isolated after inoculation of an erythroleukemia virus, Friend (F) MuLV, were derived from different endogenous sequences than those isolated after inoculation of a lymphocytic leukemia virus, Moloney (M) MuLV. This finding has been confirmed using an immunofluorescence assay to analyze the frequency of recombinant MuLV types present in large virus populations from infected mice. Further studies have indicated that pseudotyping of the ecotropic virus by envelope proteins of polytropic viruses correlated with the development of lymphocytic leukemia. Pseudotyping yeilds ecotropic virions with an altered range of infectivity and may facilitate the infection of cells which ultimately become transformed. Ecotropic pseudotyping may rreflect the generation of specific types of polytropic viruses. AKR mice harbor an endogenous ecotropic virus which recombines with endogenous nonecotropic sequences to generate oncogenic polytropic viruses. These recombinant viruses possess two nonecotropic sequences; one corresponding to the 5' end of the envelope gene (env), and another which includes the long terminal repeat (LTR). The nonecotropic sequences are thought to be derived from two different retroviral species. Intermediates have been described which contain the LTR sequence, however the source of the 5' env sequence was not known. We have identified an intermediate containing the 5' env sequence in young AKR mice.

逆转录病毒通常会发生基因改变。 这些包括点 突变，已在慢病毒（例如 visna）中记录到， EIAV 和艾滋病病毒，以及宿主基因的重大替换 已记录有鼠白血病病毒（MuLV）。 生态热带 MuLV（仅感染小鼠细胞的 MuLV）与 小鼠的内源序列产生多向病毒（MuLV） 感染其他物种的细胞）。 该项目的主要目标是 表征亲嗜性 MuLV 和基因之间产生的重组 MuLV 小鼠序列，并确定它们在疾病过程中的作用。 初步研究表明，多向性 MuLV 在 红白血病病毒 Friend (F) MuLV 的接种源自 与接种后分离的内源序列不同 淋巴细胞白血病病毒，莫洛尼 (M) MuLV。 这一发现已被 使用免疫荧光测定法分析频率证实 重组 MuLV 类型存在于来自感染者的大量病毒群体中 老鼠。 进一步的研究表明，生态热带的假型化 病毒由多向病毒的包膜蛋白与相关 淋巴细胞白血病的发展。 假型产生共嗜性病毒体 具有改变的传染性范围，并可能促进感染 最终转化的细胞。 生态性假型可能 r反映特定类型的多向病毒的产生。 AKR 小鼠携带内源性亲嗜性病毒，该病毒与 内源性非共亲性序列产生致癌多向性 病毒。 这些重组病毒具有两个非共亲性序列；一 对应于包膜基因 (env) 的 5' 端，另一个 包括长末端重复序列 (LTR)。 非共亲序列是 被认为源自两种不同的逆转录病毒物种。 中间体 已经描述了包含 LTR 序列，但是其来源 5' env 序列未知。 我们已经确定了一个中间体 含有年轻 AKR 小鼠的 5' env 序列。