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: 3963053
• 负责人: S K RUSCETTI
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 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/3963053
• 关键词: B lymphocyte; Friend virus; cell differentiation; cell growth regulation; disease /disorder model; erythroleukemia; gene expression; genetic mapping; molecular oncology; monoclonal antibody; nucleic acid sequence; oncogenes; oncogenic virus; tissue /cell culture; viral leukemia; virus envelope; virus genetics; virus replication

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.

研究的目的是试图了解小鼠 白血病病毒诱导红系转化，并理解为什么一些 品系的小鼠对一种或多种恶性疾病具有抵抗力 进程。 急性红白血病诱发病毒脾的研究 焦点形成病毒(SFFV)，专注于确定哪种病毒 致病性和红系细胞的致病基因序列 专一性。我们的数据显示，长末端的序列 猪瘟病毒的重复(LTR)区不能决定猪的红细胞嗜性 该病毒及其外膜基因在无其他病毒情况下表达 SFFV基因和SFFV LTR是致病的。因此，它的主要作用是 红系细胞上的SFFV，这是为了改变细胞的要求 对于红系激素有促红细胞生成素，是由于其产物 环境基因。为了进一步了解病毒env基因产物可能的作用 为此，我们一直在研究病毒的变种，SFFV-P和SFFV-A，它们 两者均可诱发小鼠急性红白血病，但对小鼠的影响不同 红系细胞以及它们的翻译后修饰 Env基因产物。通过在SFFV-P和SFFV-A之间进行重组，我们 已经能够定位负责生物和 这两种病毒在678个碱基区的生化差异 外膜基因的3‘端区域。 早期红白血病易感性的遗传学研究 小鼠白血病病毒以前集中在一种基因上 在5号染色体上发现编码一种与病毒包膜蛋白相关的病毒包膜蛋白 水貂细胞病灶诱导病毒。人们正在试图授予 利用该基因的遗传转移对白血病的抗性及其应用 这种小鼠模型用于抵抗治疗人类疾病等 艾滋病。