MECHANISMS OF COXASACKIEVIRUS INDUCED POLYMYOSITIS

柯萨奇病毒B1诱导小鼠慢性多发性肌炎的实验研究 提供了一种有用的病毒诱导的自身免疫模型，并且高度 与人类疾病有关的临床病程和组织病理学 与人类多发性肌炎极为相似。该模型还包含许多 与自身免疫性疾病相关的属性，包括组织嗜性， 近交系小鼠之间的易感性差异，以及专性 T细胞的参与。CVB1的肌病株和非肌病株有 已被确认身份。初步数据表明，CVB1 RNA在 在疾病的慢性期影响肌肉，当病毒不能 在培养中恢复的时间更长。有关小核糖核酸病毒的详细资料 基因组组织与克隆感染性c DNA的能力相结合 这是一个理想的检测发病分子机制的系统。 初步研究将涉及构建cdna克隆和嵌合体以 详细检查CVB1 RNA在特定组织中的持久性 原位杂交和聚合酶链式反应技术 持续性与骨骼免疫攻击的关系 肌肉。第二组实验将探索存在哪些差异 在肌病和非肌病CVB1株的基因组RNA中 这些差异与引起慢性炎症的能力有关 肌肉。这些实验的结果应该提供重要的 将通过以下方式加强我们对该机制的理解的信息 其中的CVB1诱导免疫介导性肌炎。

The induction of chronic polymyositis in mice by Coxsackievirus B1 (CVB1) provides a useful model of virus-induced autoimmunity and is highly relevant to human disease in that the clinical course and histopathology closely resemble human polymyositis. The model also encompasses many attributes associated with autoimmune diseases including tissue tropism, differences in susceptibility among inbred mouse strains, and obligate participation of T cells. Myopathic and nonmyopathic strains of CVB1 have been identified. Preliminary data indicate that CVB1 RNA persists in influenced muscle in the chronic stage of the disease when virus can no longer be recovered in culture. Detailed information on picornavirus genome organization coupled with the ability to clone infectious cDNA make this an ideal system to examine molecular mechanisms of pathogenesis. Initial studies will involve construction of cDNA clones and chimeras to examine in detail the persistence of CVB1 RNA in specific tissues using in situ hybridization and polymerase chain reaction techniques and determine the relationship between persistence and immunologic attack on skeletal muscle. The second set of experiments will explore what differences exist in the genomic RNA of myopathic and nonmyopathic CVB1 strains and which of these differences relate to the ability to cause chronic inflammation in muscle. The results of these experiments should provide important information that will enhance our understanding of the mechanism through which CVB1 induces an immunologically mediated myositis.