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: 4691881
• 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/4691881
• 关键词: Friend virus; cell differentiation; cell growth regulation; 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 been several-fold. Comparisons of the molecular structure of two variants, SFFV-P and SFFV-A, and formation of a recombinant virus have allowed localization of a region within the envelope gene that determines the ability of infected cells to differentiate in response to erythropoietin. Other experiments have shown that the long terminal repeat (LTR) region of SFFV, unlike Friend murine leukemia virus, does not carry sequences required for tissue-specific induction of leukemia, since a number of different LTRs can be substituted without affecting the disease latency of phenotype. And finally, the generation of helper-free SFFVs using a packaging cell line has provided proof that helper virus is not required for in vitro transformation of erythroid cells, first state acute erythroleukemia in mice or development in vivo of second stage tumorigenic cells. Studies on the genetics of susceptibility to early erythroleukemia induced by Friend murine leukemia virus have identified a gene on chromosome 5, at or near the Rmcf locus, that plays a major role in resistance of mice to this disease by preventing the replication of mink cell focus-inducing (MCF) viruses, believed to be the proximal cause of the disease. This gene is believed to be either a structrual gene or a regulatory gene for an MCF virus-related envelope glycoprotein that appears to block the cell surface receptor for MCF viruses. Additional genes, acting through unknown mechanisms, may also be involved in resistance.

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 Focus-forming virus（SFFV）是一种病毒。 的比较 两种变体SFFV-P和SFFV-A的分子结构，以及 重组病毒允许在包膜内定位一个区域 决定受感染细胞分化能力的基因， 对促红细胞生成素的反应 其他实验表明， SFFV末端重复（LTR）区，不同于Friend鼠白血病病毒， 不携带组织特异性诱导 白血病，因为许多不同的LTR可以被取代， 影响表型的疾病潜伏期。 最后， 使用包装细胞系的无辅助因子SFFV提供了证据， 红系细胞体外转化不需要辅助病毒 细胞，小鼠中的第一状态急性红白血病或 第二阶段肿瘤细胞。 诱导早期红白血病易感性的遗传学研究 Friend的小鼠白血病病毒在5号染色体上发现了一个基因， 或靠近Rmcf基因座，在小鼠抵抗 这种疾病通过阻止貂细胞的复制焦点诱导 (MCF)病毒，被认为是该疾病的近因。 该基因 被认为是MCF的结构基因或调节基因 一种病毒相关的包膜糖蛋白，似乎能阻断细胞表面 MCF病毒的受体。 额外的基因，通过未知的 机制，也可能参与抵抗。