MOLECULAR BASIS FOR THE ACUTE ERYTHROLEUKEMIAS INDUCED BY MURINE RETROVIRUSES

研究的目的是试图了解 小鼠白血病病毒诱导红细胞转化， 为什么某些品系的小鼠对一个或多个阶段的 恶性过程 急性红白血病脾灶形成病毒的研究 （SFFV）已经集中精力了解这种病毒如何消除 促红细胞生成素（Epo）的需求。独特的信封 SFFV编码的一种糖蛋白已被证明对此负责 生物学效应，我们现在显示使用分子重组体， SFFV的变体，其序列存在于SFFV的跨膜结构域中， 病毒包膜糖蛋白是使细胞 独立于时代。旨在了解SFFV的机制的研究 改变红系细胞的Epo需求应该得到我们的帮助。 最近的观察表明，Epo依赖性红白血病细胞系可以 通过感染SFFV使Epo-independent。如前所示， 来自SFFV感染小鼠的脾细胞，因子非依赖性的诱导 在这些细胞中，SFFV似乎不涉及经典的自分泌 与促红细胞生成素有关的机制然而，这些不依赖因子的细胞最终 获得产生独特生长因子的能力， 他们的成长。使用Epo依赖性红白血病细胞系及其 SFFV感染的对应物，我们没有发现蛋白诱导的证据 通过Epo或SFFV的酪氨酸磷酸化。 致红白血病易感性的遗传学研究 朋友MuLV继续专注于Rmcf基因座，该基因座编码或 调节MCF相关包膜糖蛋白的表达。我们 最近的数据表明，这种蛋白质可能是由一种修饰的 多嗜性前病毒存在于Rmcfr小鼠但不存在于Rmcfs小鼠中。在 在其他研究中，我们发现Rmcf基因也影响对 Moloney MuLV诱发的胸腺淋巴瘤。

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. Studies on the acute erythroleukemia-inducing spleen focus-forming virus (SFFV) have concentrated on understanding how this virus abrogates the erythropoietin (Epo) requirement of erythroid cells. The unique envelope glycoprotein encoded by SFFV has been shown to be responsible for this biological effect and we now show using molecular recombinants between variants of SFFV that sequences present in the transmembrane domain of the viral envelope glycoprotein are essential for rendering the cells Epo-independent. Studies designed to understand the mechanism by which SFFV alters the Epo requirements of erythroid cells should be aided by our recent observation that an Epo-dependent erythroleukemia cell line can be rendered Epo-independent by infection with SFFV. As previously shown with spleen cells from SFFV-infected mice, the induction of factor-independence in these cells by SFFV does not appear to involve a classical autocrine mechanism involving Epo. The factor-independent cells, however, eventually acquire the ability to produce a unique growth factor that may contribute to their growth. Using the Epo-dependent erythroleukemia cell line and its SFFV-infected counterpart, we can find no evidence of induction of protein tyrosine phosphorylation by either Epo or SFFV. Studies on the genetics of susceptibility to erythroleukemia induced by Friend MuLV continue to concentrate on the Rmcf locus, which encodes or regulates the expression of an MCF-related envelope glycoprotein. Our recent data indicate that this protein may be encoded by a modified polytropic provirus that is present in Rmcfr mice but not Rmcfs mice. In other studies, we show that the Rmcf gene also effects susceptibility to the thymic lymphoma induced by Moloney MuLV.