MOLECULAR BASIS FOR THE ACUTE ERYTHROLEUKEMIAS INDUCED BY MURINE RETROVIRUSES

研究的目的是试图了解小鼠 白血病病毒诱导红系转化，并理解为什么一些 品系的小鼠对一种或多种恶性疾病具有抵抗力 进程。 急性红白血病诱发病毒脾的研究 病灶形成病毒(SFFV)，已经翻了好几倍。两个版本之间的比较 两个变异体SFFV-P和SFFV-A的分子结构及A的形成 重组病毒使包膜内的一个区域得以定位 决定感染细胞分化能力的基因 对促红细胞生成素的反应。其他实验已经表明，长时间的 与Friend鼠白血病病毒不同，SFFV末端重复序列(LTR)区域， 不携带组织特异性诱导所需的序列 白血病，因为许多不同的LTrs可以在没有 影响疾病潜伏期的表型。最后，新一代 使用包装细胞系的无辅助SFFV提供了证据 辅助病毒不是红系体外转化所必需的 细胞，小鼠急性红白血病或在体内发展的第一状态 第二阶段的致瘤细胞。 早期红白血病易感性的遗传学研究 Friend小鼠白血病病毒在5号染色体上发现了一个基因，在 或在Rmcf基因座附近，这对小鼠的抗性起着主要作用 本病通过阻止水貂细胞的复制而引起病灶 (Mcf)病毒，据信是该病的近端原因。这个基因 被认为是MCF的结构基因或调节基因 病毒相关的包膜糖蛋白，似乎能阻断细胞表面 MCF病毒的受体。其他基因，通过未知的方式发挥作用 机制，也可能参与抗药性。

Studies have been aimed at trying to understand mechanisms by which murine leukemia viruses induce erythroid transformation and to understand why some strains of mice are resistant to one or more of the stages of the malignant process. Investigations on the acute erythroleukemia-inducing virus, spleen focus-forming virus(SFFV), have been several-fold. Comparisons of the molecular structure of two variants, SFFV-P and SFFV-A, and formation of a recombinant virus have allowed localization of a region within the envelope gene that determines the ability of infected cells to differentiate in response to erythropoietin. Other experiments have shown that the long terminal repeat (LTR) region of SFFV, unlike Friend murine leukemia virus, does not carry sequences required for tissue-specific induction of leukemia, since a number of different LTRs can be substituted without affecting the disease latency of phenotype. And finally, the generation of helper-free SFFVs using a packaging cell line has provided proof that helper virus is not required for in vitro transformation of erythroid cells, first state acute erythroleukemia in mice or development in vivo of second stage tumorigenic cells. Studies on the genetics of susceptibility to early erythroleukemia induced by Friend murine leukemia virus have identified a gene on chromosome 5, at or near the Rmcf locus, that plays a major role in resistance of mice to this disease by preventing the replication of mink cell focus-inducing (MCF) viruses, believed to be the proximal cause of the disease. This gene is believed to be either a structrual gene or a regulatory gene for an MCF virus-related envelope glycoprotein that appears to block the cell surface receptor for MCF viruses. Additional genes, acting through unknown mechanisms, may also be involved in resistance.