MOLECULAR BASIS FOR THE ACUTE ERYTHROLEUKEMIAS INDUCED BY MURINE RETROVIRUSES

使用三种不同的系统，研究的目的是了解 逆转录病毒引起小鼠红白血病的机制 确定对生物多样性至关重要的病毒和宿主基因 观察到效果。 急性红白血病诱发小鼠Friend脾病灶形成的研究 病毒专注于了解病毒包膜蛋白是如何 取消红系细胞的促红细胞生成素(EPO)需求。这个 蛋白质似乎与EPO受体相互作用并触发，并且 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促红细胞生成素启动的信号。 我们也一直在研究另一种病毒的影响 红白血病诱导病毒，含Gag-MYB-ETS的ME26病毒，ON 造血细胞生长。我们的结果表明，这种病毒，即 编码一种DNA结合蛋白，可能激活EPO受体 不成熟的造血细胞，正常情况下不表达它。病毒， 然而，可能不是直接反式激活EPO受体，但可能是 通过另一个红系特异基因GATA-1发挥作用。 第三种红白血病诱导病毒Friend MuLV的研究已经完成 是双重的。我们已经从分子上克隆了一个宿主基因的候选基因， Rmcf-r参与诱导的早期红白血病耐药 目前正在检测其生物活性。我们还有 分子克隆了Friend MuLV的变种PVC-211，它不再 在小鼠中引起红白血病，但这会导致进行性 神经退行性疾病。我们现在正在产生重组体 Pvc-211和野生型Friend MuLV，以便本地化 导致白血病或神经系统疾病的病毒基因组 疾病。

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.