MOLECULAR BASIS FOR THE ERYTHROLEUKEMIAS INDUCED BY MURINE RETROVIRUSES

鼠逆转录病毒引起的红白血病的分子基础

• 批准号: 3752710
• 负责人: S K RUSCETTI
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 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/3752710
• 关键词: DNA binding protein; Friend leukemia; Friend virus; biological signal transduction; cell growth regulation; erythroid stem cell; erythroleukemia; erythropoietin; gene expression; genetic strain; host organism interaction; laboratory mouse; molecular cloning; molecular oncology; neoplasm /cancer genetics; oncogenic virus; phosphoproteins; phosphorylation; transcription factor; viral leukemogenesis; virus envelope

Using mouse model systems, studies have been carried out to determine how non-oncogene-containing retroviruses cause erythroleukemia and why certain mice are resistant to the pathogenic process. The Friend spleen focus-forming virus (SFFV) causes a rapid erythroleukemia due to the unique envelope gene that it carries. The SFFV envelope glycoprotein alters the growth of erythroid cells by rendering the cells independent of the erythroid hormone erythropoietin (Epo). In order to determine whether the SFFV envelope glycoprotein is activating the Epo signal transduction pathway, studies were carried out to compare erythroid cells stimulated with Epo or infected with SFFV for expression of tyrosine- phosphorylated proteins and DNA-binding proteins. Both Epo and SFFV were shown to induce the tyrosine phosphorylation of several common substrates, one of which appears to be a DNA-binding protein related to the class of transcription factors designated STAT proteins. No differences could be detected in the Epo signal transduction pathways between strains of mice that are resistant or susceptible to the effects of SFFV. Studies were also carried out on a mouse resistance gene, Rmcfr, that prevents the development of erythroleukemia induced by Friend murine leukemia virus (F-MuLV). It was previously shown that F-MuLV- induced erythroleukemia requires the generation and replication of polytropic MuLVs. Molecular cloning of the Rmcf resistance gene now indicates that it is the envelope gene of an endogenous modified polytropic virus. Expression of this gene apparently blocks infection of polytropic MuLVs by a mechanism analogous to viral interference.

使用小鼠模型系统，已经进行了研究以确定如何 非癌基因逆转录病毒引起红白血病，为什么 某些小鼠对致病过程具有抵抗力。 朋友的脾 病灶形成病毒（SFFV）引起快速红白血病， 它携带的独特的包膜基因 SFFV包膜糖蛋白 通过使红细胞独立， 促红细胞生成素（Epo）。 为了确定 SFFV包膜糖蛋白是否激活Epo信号 转导途径，进行研究以比较红系细胞 用Epo刺激或用SFFV感染以表达酪氨酸- 磷酸化蛋白和DNA结合蛋白。 Epo和SFFV均为 显示诱导几种常见的酪氨酸磷酸化 底物，其中之一似乎是一种DNA结合蛋白， 称为STAT蛋白的一类转录因子。 没有 在Epo信号转导通路中可以检测到差异 在抵抗或敏感的小鼠品系之间 关于SFFV 还对小鼠抗性基因进行了研究， Rmcfr，可预防Friend诱导的红白血病的发展 鼠白血病病毒（F-MuLV）。 先前表明F-MuLV- 诱导的红白血病需要产生和复制 多变性MuLV。 Rmcf抗性基因的分子克隆 表明它是内源性修饰的 多变性病毒 这种基因的表达显然阻止了感染 通过类似于病毒干扰的机制对多变MuLV进行抑制。