ROLE OF ENDOGENOUS AND RECOMBINANT RETROVIRUSES IN LEUKEMIA AND DIFFERENTIATION

内源性和重组逆转录病毒在白血病和分化中的作用

• 批准号: 3960506
• 负责人: B W CHESEBRO
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 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/3960506
• 关键词: Friend leukemia; Friend virus; cell differentiation; cellular oncology; erythroleukemia; gene expression; genetic recombination; genetic strain; helper virus; hemolytic anemia; leukemia virus; lymphocytic leukemia; molecular cloning; molecular oncology; monoclonal antibody; myelogenous leukemia; newborn animals; viral leukemia; viral leukemogenesis; virulence; virus RNA; virus classification; virus envelope; virus genetics; virus infection mechanism; virus virus interaction

The main goal of this project is to define different retrovirus-induced pathogenic mechanisms both at the cellular level in intact animals and at the molecular or biochemical level. Retrovirus-induced hemolytic anemia has been found to be an important early pathogenic effect after inoculation of newborn mice with Friend murine leukemia helper virus (F-MuLV). This effect was previously undetected because the main clinical signs of anemia and splenomegaly were identical both in the early hemolytic phase and in the late erythroleukemia phase of the disease. These stages were distinguished in the present work by reticulocyte counts showing high levels during hemolysis and low levels during leukemia. Two closely related F-MuLV strains have been found to differ in their ability to induce both of these pathogenic effects, the lower virulence strain inducing only mild hemolysis and having a very prolonged latency of induction of leukemia. Molecular cloning of this low virulence virus strain has been done in our laboratory and recombinant retroviruses were constructed using the low and high virulence strains. The results indicated that the severity of the early and late pathogenic effects could be dissociated in certain recombinant viruses. This suggested that different portions of the viral genome were responsible for each of these phases of the disease.

该项目的主要目标是定义不同的逆转录病毒诱导的 完整动物细胞水平和 分子或生化水平。 逆转录病毒引起的溶血性贫血 已被发现是接种后重要的早期致病效应 携带 Friend 鼠白血病辅助病毒 (F-MuLV) 的新生小鼠。 这 以前未发现这种效应，因为贫血的主要临床症状 和脾肿大在早期溶血期和溶血期均相同。 该疾病的晚期红白血病阶段。 这些阶段是 在目前的工作中，网织红细胞计数显示出高 溶血期间的水平和白血病期间的低水平。 两人亲密 相关的 F-MuLV 菌株被发现在诱导能力上有所不同 这两种致病作用，毒力较低的菌株仅诱导 轻度溶血并具有很长的诱导潜伏期 白血病。 这种低毒力病毒株的分子克隆已被 在我们的实验室完成并使用构建重组逆转录病毒 低毒力菌株和高毒力菌株。 结果表明， 早期和晚期致病作用的严重程度可以在 某些重组病毒。 这表明，不同部分的 病毒基因组导致了疾病的每个阶段。