MECHANISMS OF COXASACKIEVIRUS INDUCED POLYMYOSITIS

柯萨奇B1病毒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， 与人类疾病相关的临床过程和组织病理学 与人类多发性肌炎非常相似 该模型还包括许多 与自身免疫性疾病相关的属性包括组织嗜性， 近交系小鼠品系之间的易感性差异， T细胞的参与。 CVB 1的肌病和非肌病菌株具有 被识别。 初步数据表明，CVB1 RNA持续存在于 在疾病的慢性阶段，当病毒不能 在文化中恢复。 关于picornavirus的详细信息 基因组结构加上克隆感染性cDNA的能力， 这是一个理想的系统，以检查发病机制的分子机制。 初步研究将涉及构建cDNA克隆和嵌合体， 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反应技术 持续性与骨骼肌免疫攻击关系 肌肉. 第二组实验将探讨存在哪些差异 在肌病和非肌病CVB1菌株的基因组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 这些信息将通过以下方式增进我们对该机制的了解： 其中CVB 1诱导免疫介导的肌炎。

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.