MOLECULAR BASIS FOR THE ACUTE ERYTHROLEUKEMIAS INDUCED BY MURINE RETROVIRUSES

研究的目的是试图通过以下方式来了解其机制： 哪些鼠白血病病毒诱导红系转化， 为了了解为什么某些品系的小鼠对一种或多种 恶性过程的各个阶段。 急性红细胞白血病致脾灶的研究 形成病毒（SFFV）已经集中在了解这是如何 病毒改变红系细胞的生长和分化。 SFFV感染小鼠红系细胞与正常小鼠不同 红系细胞，因为它们可以增殖和分化， 明显缺乏红细胞激素促红细胞生成素（Epo）。 SFFV携带的独特包膜基因已被证明是 负责病毒的生物效应。 我们最近 结果表明，SFFV感染的红系细胞既不分泌 一种红细胞生长因子， 自分泌样的方式，也不使可检测水平的Epo特异性 mRNA。 此外，SFFV感染的红系细胞与未感染的红系细胞相比， 在数量、亲和力或大小上与正常对应物不同， 他们的Epo受体 因此，SFFV不会改变激素水平， 红系细胞在Epo水平或其 受体的 红白血病易感基因的研究 由Friend MuLV诱导的基因集中在一个先前 在5号染色体上，在Rmcf基因座处或附近鉴定，其编码 一种与貂细胞灶相关的病毒包膜糖蛋白， 诱导病毒。 RNA转录本已经在组织中被鉴定 来自可能编码这种包膜糖蛋白的耐药小鼠， 该假定抗性基因的cDNA克隆正在进行中。

Studies have been aimed at trying to understand the mechanisms by which murine leukemia viruses induce erythroid transformation and to understand why some strains of mice are resistant to one or more stages of the malignant process. Investigations on the acute erythroleukemias-inducing spleen focus- forming virus (SFFV) have concentrated on understanding how this virus alters the growth and differentiation of erythroid cells. Erythroid cells form SFFV-infected mice differ form normal erythroid cells in that they can proliferate and differentiate in the apparent absence of the erythroid hormone erythropoietin (Epo). The unique envelope gene carried by SFFV has been shown to be responsible for the biological effects of the virus. Our recent results indicate that SFFV-infected erythroid cells neither secrete an erythroid growth factor that stimulates their growth in an autocrine-like manner nor make detectable levels of Epo-specific mRNA. In addition, SFFV-infected erythroid cells do not differ from their normal counterparts in the number, affinity or size of their Epo receptors. Thus, SFFV is not altering the hormonal requirements of erythroid cells at the level of Epo or its receptor. Studies on the genetics of susceptibility to erythroleukemia induced by Friend MuLV are concentrating on a gene previously identified on chromosome 5, at or near the Rmcf locus, that encodes a viral enveloe glycoprotein related to that of mink cell focus- inducing viruses. RNA transcripts have been identified in tissues from resistant mice that may encode this envelope glycoprotein and cDNA cloning of this putative resistance gene is in progress.