GENETIC STRUCTURE OF MURINE RETROVIRUSES

该项目的主要重点是改变基因， 逆转录病毒作为重组和点突变的结果。 等 变异产生混合逆转录病毒感染， 所有体内逆转录病毒感染。 其中包括HIV和HTLV 感染，导致艾滋病和人类T细胞白血病， 鼠逆转录病毒感染经常导致增殖性， 免疫学或神经系统疾病。 我们最近的研究 研究了混合体内逆转录病毒感染的影响， 用鼠白血病病毒（MuLV）的混合物共接种小鼠。 嗜亲性MuLV感染通常导致新生 产生多嗜性MuLV，其是两种病毒之间的重组体。 接种的亲嗜性MuLV和内源性嗜多性MuLV包膜基因 存在于近交系小鼠的基因组中。 重组多效性 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， 来自嗜亲性MuLV。我们发现用混合物感染小鼠 多嗜性MuLV和嗜亲性MuLV的结果几乎完全 抑制多嗜性MuLV的从头产生。 我们的结果 表明两种病毒最初感染的是同一小群人 单核细胞/巨噬细胞谱系的细胞，并表明在体内 在感染的这个阶段进行干预可以防止进一步的感染， 病毒的传播。 进一步的研究将确定小细胞是否 人群是其他类型逆转录病毒的初始靶点， 研究这种细胞的感染是否是有效 感染老鼠。

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.