BASIS FOR DIABETOGENICITY OF ENCEPHALOMYOCARDITIS VIRUS

脑心肌炎(EMC)病毒诱导的小鼠糖尿病 类似于人类青少年发病的糖尿病。两个其他方面相似的人 EMC病毒的变种可用于研究，这些变种的 干扰素诱导颗粒(IFP)表型及其致病能力 小鼠的糖尿病。EMC-B变种是IFP+，可产生高水平的 感染小鼠体内循环中的干扰素可造成有限的破坏 而且不会导致糖尿病。当循环中的干扰素 被抗干扰素球蛋白中和后，糖尿病是由感染 EMC-B表明干扰素系统，可能是IFP表型，是 糖尿病预后的决定因素。EMC-D变种是IFP-，生产 低水平的循环干扰素；破坏胰岛并导致 小鼠的糖尿病。关键的遗传差异肯定是造成这些 不同的生物特性。我们建议通过以下方式研究这一问题 B和D变异体基因的合成和克隆。哺乳动物细胞 将用基因组的cdna拷贝和由此产生的病毒 将被检查以验证生物差异的基础 已经被克隆了。将对B和D基因组进行三次比较 技术：限制图谱，嵌合分子的合成和 基因产品的分析。基因组中存在差异的部分 将对其进行测序和详细比较。从以下来源获得的数据 本项目将提供对干扰素机制的理解。 病毒的诱导和EMC病毒致糖尿病的基础。

Encephalomyocarditis (EMC) virus induced diabetes mellitus in mice is similar to juvenile onset diabetes in humans. Two otherwise similar variants of EMC virus are available for study that differ in their interferon inducing particle (IFP) phenotype and in their ability to cause diabetes in mice. The EMC-B variant is ifp+, produces high levels of circulating interferon (IFN) in infected mice, causes limited destruction of pancreatic islets and does not cause diabetes. When circulating IFN is neutralized by anti-IFN globulins, diabetes results from infection with EMC-B indicating that the interferon system, possibly the IFP phenotype, is a determinant of the diabetic outcome. The EMC-D variant is ifp-, produces lower levels of circulating IFN; destroys pancreatic islets and causes diabetes in mice. Key genetic differences must be responsible for these different biological properties. We propose to examine this question by synthesizing and cloning the cDNA of the B and D variants. Mammalian cells will be transfected with cDNA copies of the genome and the resulting virus will be examined to verify that the basis for the biological differences has been cloned. The B and D genomes will be compared by three techniques: restriction mapping, synthesis of chimeric molecules and analysis of gene products. Portions of the genome in which differences appear to lie will be sequenced and compared in detail. Data gained from this project will provide an understanding of the mechanism of IFN induction by viruses and of the basis for the diabetogenicity of EMC virus.