MOLECULAR BASIS FOR THE ACUTE ERYTHROLEUKEMIAS INDUCED BY MURINE RETROVIRUSES

鼠逆转录病毒引起的急性红白血病的分子基础

• 批准号: 3853551
• 负责人: S K RUSCETTI
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 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/3853551
• 关键词: Friend leukemia; erythroid stem cell; erythroleukemia; erythropoietin; genetic recombination; helper virus; hormone receptor; hormone related neoplasm /cancer; laboratory mouse; lymphoma; molecular cloning; molecular oncology; neural degeneration; provirus; viral leukemogenesis; virus envelope; virus genetics; virus protein

Using three different systems, studies have been aimed at understanding the mechanisms by which retroviruses cause erythroleukemia in mice and identifying the viral and host genes that are crucial for the biological effects observed. Studies on the acute erythroleukemia-inducing Friend spleen focus-forming virus have concentrated on understanding how the viral envelope protein abrogates the erythropoietin (Epo) requirement of erythroid cells. The protein appears to interact with and trigger the Epo receptor, and studies are in progress to determine if this interaction results in a mitogenic signal like that initiated by Epo. We have also been studying the effects of another erythroleukemia-inducing virus, the gag-myb-ets-containing ME26 virus, on hematopoietic cell growth. Our results indicate that this virus, which encodes a DNA-binding protein, may be activating the Epo receptor in an immature hematopoietic cell that does not normally express it. The virus, however, may not be directly transactivating the Epo receptor, but may be working through another erythroid-specific gene, GATA-1. Studies on the third erythroleukemia-inducing virus, Friend MuLV, have been twofold. We have molecularly cloned a candidate for a host gene, Rmcf-r, that is involved in resistance to early erythroleukemia induced by the virus, and are now testing its biological activity. We have also molecularly cloned a variant of Friend MuLV, PVC-211, which no longer causes erythroleukemia in mice, but which induces a progressive neurodegenerative disease. We are now generating recombinants between PVC-211 and wild-type Friend MuLV in order to localize the regions of the viral genome responsible for inducing either leukemia or neurological disease.

使用三种不同的系统，研究旨在了解 逆转录病毒引起小鼠红白血病的机制， 确定病毒和宿主基因，这些基因对生物学 观察到的效果。 急性红白血病诱导Friend脾灶形成的研究 病毒已经集中在了解病毒包膜蛋白如何 消除了红系细胞对促红细胞生成素（Epo）的需求。 的 蛋白质似乎与Epo受体相互作用并触发Epo受体， 研究正在进行中，以确定这种相互作用是否会导致 促有丝分裂信号类似于Epo启动的信号。 我们还研究了另一种 红白血病诱导病毒，含gag-myb-ets的ME 26病毒， 造血细胞生长 我们的研究结果表明，这种病毒， 编码一种DNA结合蛋白，可能是激活Epo受体， 通常不表达它的未成熟造血细胞。病毒， 然而，可能不直接反式激活Epo受体，但可能 通过另一个红细胞特异性基因加塔-1发挥作用。 对第三种红白血病诱导病毒Friend MuLV的研究， 是双重的。 我们已经克隆了一个宿主基因的候选基因， Rmcf-r，即参与抵抗早期红白血病诱导 目前正在测试其生物活性。 我们还 分子克隆了Friend MuLV的变体PVC-211，它不再 导致小鼠红白血病，但这会诱导进行性 神经退行性疾病 我们现在正在生产重组体， PVC-211和野生型Friend MuLV，以定位 病毒基因组负责诱导白血病或神经 疾病