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: 3809592
• 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/3809592
• 关键词: Friend leukemia; Friend virus; Retroviridae disease; central nervous system disorders; fusion gene; gene expression; genetic manipulation; genetic mapping; genetic recombination; genetic regulation; hemolytic anemia; laboratory mouse; linkage mapping; molecular cloning; neurotropic virus; nucleic acid structure; site directed mutagenesis; viral leukemia; viral leukemogenesis; virus RNA; virus envelope; virus genetics; virus infection mechanism

This project is aimed at investigation of mechanisms of pathogenesis of murine leukemia viruses. The Friend murine leukemia helper virus (F-MuLV) induces early hemolytic anemia (EHA) three weeks post inoculation of newborn mice. In contrast, Moloney murine leukemia virus (M-MuLV) does not induce severe EHA. In order to define which portions of the F-MuLV and M-MuLV genomes were responsible for the differences in induction of EHA, recombinant retroviruses were constructed exchanging different portions of the genomes of F-MuLV and M-MuLV. The results indicated that only retroviruses containing the U5-gag-pol region of F-MuLV could induce EHA. The precise sequence in this region responsible for the pathogenesis of EHA is now being defined by construction of additional recombinant retroviruses and sitespecific mutagenesis.

本项目旨在研究其发病机制， 鼠白血病病毒。Friend小鼠白血病辅助病毒（F-MuLV） 诱导早期溶血性贫血（EHA）接种后三周， 新生小鼠相比之下，莫洛尼鼠白血病病毒（M-MuLV）不 导致严重EHA。为了定义F-MuLV的哪些部分， M-MuLV基因组负责EHA诱导的差异， 构建了重组逆转录病毒， F-MuLV和M-MuLV的基因组。结果表明，只有 含有F-MuLV U 5-gag-pol区域的逆转录病毒可以诱导EHA。 负责EHA发病机制的该区域的精确序列 现在通过构建额外的重组逆转录病毒来定义 和位点特异性诱变。