ROLE OF ENDOGENOUS AND RECOMBINANT RETROVIRUSES IN LEUKEMIA AND DIFFERENTIATION

这个项目的主要目标是定义不同的由逆转录病毒引起的 在完整动物和在细胞水平上的致病机制 分子或生化水平。逆转录病毒引起的溶血性贫血 已被发现是接种后的一个重要的早期致病效应 携带Friend小鼠白血病辅助病毒(F-MuLV)的新生小鼠。这 以前没有检测到效果，因为贫血的主要临床症状 和脾肿大在溶血的早期和在 这种疾病的红白血病晚期。这些阶段是 本研究的特点是网织红细胞计数高 溶血时的水平和白血病期间的低水平。两个人关系密切 相关的F-MuLV毒株被发现在诱导 这两种致病作用，低毒力菌株只诱导 轻度溶血，并有非常长的诱导潜伏期 白血病。该低毒力病毒株的分子克隆已完成 重组逆转录病毒是在我们实验室做的，重组逆转录病毒是用 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在 某些重组病毒。这表明，不同部分的 病毒基因组对疾病的每一个阶段都负有责任。

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.