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， 小鼠品系对恶性肿瘤的一个或多个阶段具有抗性， 过程 急性红白血病诱导病毒脾的研究 焦点形成病毒（SFFV），集中在确定哪种病毒 序列负责致病性和红系细胞 的特异性 我们的数据表明长终端中的序列 SFFV的LTR区不能决定SFFV的红系细胞嗜性， 该病毒和SFFV env基因表达在其它基因不存在的情况下 SFFV基因和SFFV LTR是致病性的。 因此， SFFV对红系细胞，这是改变的要求， 有为红细胞激素促红细胞生成素，是由于其产品 env基因。 为了进一步了解病毒的env基因产物 为此，我们一直在研究病毒的变种，SFFV-P和SFFV-A， 两种药物都能诱导小鼠急性红白血病，但对 红系细胞以及它们的翻译后修饰 env基因产物。 通过制备SFFV-P和SFFV-A之间的重组体， 已经能够定位负责生物和 这两种病毒之间的生物化学差异，以678 bp的区域， 包膜基因的3'区。 诱导早期红白血病易感性的遗传学研究 由朋友鼠白血病病毒集中在一个基因以前 在5号染色体上鉴定出编码病毒包膜蛋白， 水貂细胞病灶诱导病毒的感染。 我们正试图 通过遗传转移该基因来抵抗白血病，以及应用 这种小鼠模型对人类疾病的治疗具有抗性， 艾滋病

Studies have been aimed at trying to understand mechanisms by which murine leukemia viruses induce erythroid transformation and to understand why some strains of mice are resistant to one or more of the stages of the malignant process. Investigations on the acute erythroleukemia-inducing virus, spleen focus-forming virus (SFFV), have concentrated on determining which viral sequences are responsible for pathogenicity and erythroid cell specificity. Our data have shown that sequences in the long terminal repeat (LTR) region of SFFV do not determine the erythroid cell tropism of the virus and that expression of the SFFV env gene in the absence of other SFFV genes and the SFFV LTR is pathogenic. Thus, the primary effect of SFFV on erythroid cells, which is to alter the requirement that the cells have for the erythroid hormone erythropoietin, is due to the product of its env gene. To further understand how the viral env gene product may do this, we have been studying variants of the virus, SFFV-P and SFFV-A, which both induce acute erythroleukemia in mice but differ in their effects on erythroid cells as well as in the post-translational modification of their env gene products. By making recombinants between SFFV-P and SFFV-A, we have been able to localize the sequences responsible for the biological and biochemical differences between these two viruses to a 678 bp region in the 3' region of the envelope gene. Studies on the genetics of susceptibility to early erythroleukemia induced by Friend murine leukemia virus are concentrating on a gene previously identified on chromosome 5 that encodes a viral envelope protein related to that of mink cell focus-inducing virus. Attempts are being made to confer resistance to leukemia by genetic transfer of this gene as well as to apply this mouse model for resistance to the treatment of human diseases such as AIDS.