STUDIES OF COXSACKIEVIRUS-INDUCED MYOCARDITIS

小鼠接种柯萨奇病毒B3（CVB 3）会导致心肌炎 局灶性单核细胞对病毒感染细胞的炎症反应 心脏组织 涉及细胞毒性T细胞的迟发型超敏反应 淋巴细胞（CTL）对病毒诱导的表面抗原（新抗原）的反应 与这个人类疾病的优秀模型有关。 我们提出 使用特异性免疫荧光分析来识别心脏中的细胞， 感染并携带新抗原和单核细胞的组织 在心肌炎形成期间对新抗原应答的细胞类型 病变 柯萨奇病毒B3感染小鼠新生皮肤成纤维细胞（MNSF）， 作为CVB 3接种心肌炎小鼠CTL的靶点，表明 存在新抗原。 我们将使用MNSF作为组织培养来源， 新抗原，并通过免疫组织化学方法鉴定、分离和表征新抗原。 各种生化和免疫学技术。 单克隆抗体 将针对MNSF新抗原开发，用于时间 相对于病毒，在MNSF表面上出现新抗原 复制，遗传起点，表达的心脏细胞类型 新抗原和新抗原在疾病过程中的作用。 我们将 鉴定和确定血清中因子的作用机制， 对CVB 3诱导的心肌炎具有抗性的小鼠，在转移到 正常小鼠，给予保护。 我们将研究 抗柯萨奇病毒B3抗体独特型抗血清 改善CVB 3诱导的心肌炎。 的作用机制， 将评估抗心肌病碱类似物。 可能发挥的作用 抑制细胞在预防心肌炎中的作用将用 X射线照射的小鼠供体或受体和来自几种类型的淋巴细胞 对CVB3诱导的心肌炎有抵抗力的小鼠。 在上述所有中 研究，一个独特的收集同基因型心肌或心肌 CVB3的变体将用于提供有关 新抗原，抑制细胞的可能作用和 单核细胞参与心肌炎。 我们将使用生化 方法来确定是否存在差异的毒力之间的心肌肌 心肌炎变异的CVB 3可以归因于不同的基因， 衣壳多肽。

Inoculation of mice with coxsackievirus B3 (CVB3) results in myocarditis, a focal mononuclear cell inflammatory response to virus-infected cells in heart tissue. Delayed hypersensitivity responses involving cytotoxic T lymphocyte (CTL) reactions to viral-induced surface antigens (neoantigen(s) are implicated in this excellent model for the human disease. We propose to use specific immunofluorescence assays to identify the cells in heart tissue that become infected and bear the neoantigen(s) and the mononuclear cell types that respond to neoantigen(s) during formation of myocarditic lesions. Murine neonatal skin fibroblasts (MNSF) infected with CVB3 serve as targets for CTL from CVB3-inoculated myocarditic mice, indicating the presence of neoantigen(s). We will use MNSF as a tissue culture source for neoantigen(s) and identify, isolate and characterize the neoantigen(s) by a variety of biochemical and immunological techniques. Monoclonal antibodies will be developed against MNSF neoantigen(s) for use in studies on temporal appearance of neoantigen(s) on the surface of MNSF relative to virus replication, genetic origin, type of heart cell expressing the neoantigen(s) and role of neoantigen(s) in the disease process. We will identify and determine the mechanism of action of a factor(s) in sera from mice resistant to CVB3-induced myocarditis which can, upon transfer to normal mice, confer protection. We will investigate the mechanism by which anti-idiotypic antiserum against anti-CVB3 antibody prophylactically ameliorates CVB3-induced myocarditis. The mechanism of action of an antimyocarditic base analogue will be assessed. The possible role of suppressor cells in preventing myocarditis will be examined using x-irradiated murine donors or recipients and lymphocytes from several types of mice resistant to CVB3-induction of myocarditis. In all of the above studies, a unique collection of isogenic amyocarditic or myocarditic variants of CVB3 will be used to provide information on the nature of the neoantigen(s), the possible role of suppressor cells and the types of mononuclear cells participating in myocarditis. We will use biochemical methods to determine whether differences in virulence between amyocarditic and myocarditic variants of CVB3 can be attributed to differences in a capsid polypeptide(s).