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: 3939331
• 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/3939331
• 关键词: B lymphocyte; Friend virus; Retroviridae disease; cell differentiation; cell growth regulation; cell membrane; colony stimulating factor; disease /disorder model; erythroleukemia; erythropoietin; gene expression; genetic mapping; molecular oncology; monoclonal antibody; neoplasm /cancer genetics; nucleic acid sequence; oncogenes; oncogenic virus; spleen; tissue /cell culture; viral leukemia; virus envelope; virus genetics; virus replication

The Friend strain of the spleen focus forming virus (SFFV) causes an acute erythroleukemia in mice. Studies have been aimed at defining the area(s) of the viral genome responsible for pathogenicity and erythroid cell specificity and determining the mechanism by which SFFV alters erythroid cell growth and differentiation. Using a Moloney MuLV-based retroviral vector, we have demonstrated that the SFFV env gene, when introduced into mice in the absence of other SFFV genes, is pathogenic. The disease induced is indistinguishabled from that induced by the entire SFFV genome, proving that the primary effect of the virus, which is to alter the requirements of erythroid cells for erythropoietin (Epo), is due solely to the product of its env gene. To further understand how the viral env gene product alters erythroid cells, we have continued our studies of variants of the virus, designated SFFVp and SFFVA, both of which induce acute erythroleukemia but differ in their effects on erythroid cells as well as in the processing of their env gene products. We were previously able to localize the biological and biochemical differences between the two viruses to a 678 bp region in the 3' half of the env gene. We have now further localized the critical region to a 120 bp fragment from the of the protein. Finally, we have attempted to understand how the SFFV envelope glycoprotein alters the requirements of erythroid cells for Epo by comparing normal and virus-infected cells for Epo receptors. Our results indicate that spleen cells from SFFVp-infected mice, which proliferate and differentiate in the apparent absence of Epo, have the same number of Epo receptors as normal erythroid cells, whereas spleen cells from SFFVA-infected mice, which proliferate better in the presence of Epo and which require Epo for differentiation, have 4 times as many Epo receptors. Cross-linking studies show no obvious quantitative differences in the receptors on normal and SFFV-infected cells.

脾病灶形成病毒（SFFV）的Friend株引起 小鼠急性红白血病 研究的目的是 定义病毒基因组的区域， 致病性和红系细胞特异性， SFFV改变红系细胞生长的机制， 分化 使用基于Moloney MuLV的逆转录病毒载体， 证明了SFFV env基因，当引入小鼠时， 在没有其他SFFV基因的情况下，是致病性的。 疾病 诱导的与整个SFFV诱导的是不一致的 基因组，证明病毒的主要作用，这是 改变红系细胞对促红细胞生成素（Epo）的需求， 完全是由于其env基因的产物。 进一步了解 病毒env基因产物如何改变红系细胞，我们有 我们继续研究命名为SFFVp的病毒变体 和SFFVA，两者都诱导急性红白血病，但 不同的是它们对红系细胞的作用以及 加工它们的env基因产物。 我们以前能够 定位生物和生物化学之间的差异， 两种病毒的env基因3 ′端一半的678 bp区域。 我们 现在已经将关键区域进一步定位到120 bp， 从蛋白质的片段。 最后，我们试图 了解SFFV包膜糖蛋白如何改变 红系细胞对Epo的需求， Epo受体的病毒感染细胞。 我们的结果表明 来自SFFV β感染小鼠的脾细胞，其增殖并 在明显缺乏Epo的情况下区分，具有相同的 正常红系细胞的Epo受体数量，而脾 来自SFFVA感染的小鼠的细胞，它们在 Epo的存在和需要Epo分化，有4 是促红细胞生成素受体的两倍 交联研究表明， 在正常人和 SFFV感染的细胞。