ROLE OF ENDOGENOUS AND RECOMBINANT RETROVIRUSES IN LEUKEMIA AND DIFFERENTIATION

该项目的主要目标是定义不同的逆转录病毒诱导的 在完整动物的细胞水平和 分子或生物化学水平。 逆转录病毒引起的溶血性贫血 已发现是接种后重要的早期致病效应 用Friend鼠白血病辅助病毒（F-MuLV）感染新生小鼠。 这 以前未检测到效果，因为贫血的主要临床体征 和脾肿大在早期溶血期和 红白血病晚期 这些阶段是 在本工作中，网织红细胞计数显示高 在溶血期间的水平和在白血病期间的低水平。 两个密切 已经发现相关的F-MuLV毒株在诱导 这两种致病作用，低毒力菌株仅诱导 轻度溶血，并具有非常长的诱导 白血病 该病毒株的分子克隆已被 在我们的实验室完成，重组逆转录病毒构建使用 低毒力菌株和高毒力菌株。 结果表明 早期和晚期致病效应的严重程度可以分离， 某些重组病毒。 这表明， 病毒基因组负责疾病的每个阶段。

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.