BASIS FOR DIABETOGENICITY OF ENCEPHALOMYOCARDITIS VIRUS

脑心肌炎（EMC）病毒诱导的小鼠糖尿病 类似于青少年糖尿病。 两个相似的 EMC病毒的变体可用于研究，这些变体在 干扰素诱导颗粒（IFP）表型和它们引起 糖尿病小鼠 EMC-B变体是ifp+，产生高水平的 感染小鼠体内循环的干扰素（IFN）造成的破坏有限 而不会导致糖尿病。 当循环IFN 被抗干扰素球蛋白中和，糖尿病是由感染 EMC-B表明干扰素系统，可能是IFP表型， 糖尿病预后的决定因素。 EMC-D变体为ifp-，产生 循环IFN水平降低;破坏胰岛， 糖尿病小鼠 关键的遗传差异必须负责这些 不同的生物特性。 我们建议研究这个问题， 合成并克隆B和D变体的cDNA。 哺乳动物细胞 将被基因组的cDNA拷贝转染， 将进行检查，以验证生物学差异的基础 被克隆了 B和D基因组将由三个 技术：限制性作图，嵌合分子的合成， 基因产物分析。 基因组的某些部分 会被详细排序和比较 数据来自 本项目将提供IFN的机制的理解， 病毒诱导和EMC病毒致糖尿病性的基础。

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.