GENETIC STRUCTURE OF MURINE RETROVIRUSES

逆转录病毒通常会发生基因改变。 其中包括点 已经用慢病毒如visna记录的突变， EIAV和AIDS病毒，以及与宿主基因的主要替换 其已经用鼠白血病病毒（MuLV）记录。 嗜亲 MuLV（仅感染鼠细胞的MuLV）经历与 小鼠的内源性序列以产生嗜多性病毒（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 小鼠的基因序列，并确定其在疾病过程中的作用。 最初的研究表明，分离后的多嗜性MuLV 红白血病病毒Friend（F）MuLV接种物来源于 不同的内源性序列比那些接种后分离的a 淋巴细胞白血病病毒，Moloney（M）MuLV。 这一发现是 使用免疫荧光测定法来分析 来自感染的大病毒群体中存在的重组MuLV类型 小鼠 进一步的研究表明，嗜亲性的假型 病毒的囊膜蛋白的多变性病毒相关的 淋巴细胞白血病的发展。 假型耶尔德嗜亲性病毒粒子 感染性范围改变，并可能促进 最终转化的细胞。 嗜亲性假型可能 反映了特定类型的多变病毒的产生。 AKR小鼠携带一种内源性嗜亲性病毒， 内源性非共嗜性序列产生致癌性多嗜性 病毒。 这些重组病毒具有两个非嗜性序列： 对应于包膜基因（env）的5'末端的另一个， 包括长末端重复序列（LTR）。 非共向性序列是 被认为来自两种不同的逆转录病毒。 中间体 已经描述了含有LTR序列的，然而， 5 ′ env序列未知。 我们发现了一个中间人 在年轻的AKR小鼠中含有5' env序列。

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.