GENETIC STRUCTURE OF MURINE RETROVIRUSES

逆转录病毒通常会发生基因改变。其中包括点 突变，已经在Visna等Lenti病毒中被记录下来， EIAV和艾滋病病毒，以及宿主基因的主要替换 它们已经被记录在小鼠白血病病毒(MULV)中。生态型 MULV(仅感染小鼠细胞的MULV)与 小鼠产生多嗜性病毒(MuLV)的内源序列 感染其他物种的细胞)。这个项目的主要目标是 生态型MuLV与基因之间产生的重组MuLV的特征 老鼠的序列，并确定它们在疾病过程中的作用。 初步研究表明，经分离的多向性MULV 接种红白血病病毒Friend(F)MuLV源于 不同于接种后分离的内源序列 淋巴细胞白血病病毒，Moloney(M)MuLV。这一发现一直是 确认使用了免疫荧光分析的频率 重组MuLV类型存在于受感染的大量病毒群体中 老鼠。进一步的研究表明，生态型的伪分型 病毒通过多嗜性病毒的囊膜蛋白与 淋巴细胞性白血病的发展。假分型Yelds生态嗜毒病毒粒子 具有改变的传染性范围，并可能促进感染 最终转化的细胞。生态亲和性伪分型可以 反映特定类型的多嗜性病毒的产生。 AKR小鼠携带一种内源性生态病毒，该病毒与 产生致癌多变性的内源性非生态性序列 病毒。这些重组病毒具有两个非生态性序列；一个 对应于包膜基因的5‘端(Env)，以及另一种 包括长末端重复序列(LTR)。非生态型序列为 被认为来自两种不同的逆转录病毒物种。中间体 已经描述了包含LTR序列的序列，然而， 5‘端的env序列未知。我们已经确定了一个中间体 在年轻的AKR小鼠中包含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.