COXSACKIE MYOCARDITIS AND VIRAL PERSISTENCE IN THE HEART

柯萨奇病毒是小核糖核酸病毒家族的重要成员 人类病原体。柯萨奇病毒B3(CVB3)是一种常见的 人类亚急性、急性和慢性心肌炎的因子。在英年华 成人CVB3感染可能导致心律失常和急性心脏 失败；慢性病可能叠加，导致扩张 心肌病，需要移植，否则会死亡。为了更好地 了解这种疾病的发病机制，几种小鼠模型系统 已经建立起来，这似乎与 人类疾病的进程。我们已经开始研究这种机制。 潜在的CVB心肌炎。这项建议的目标是：1. 进一步探讨CVB3型心肌炎的免疫决定因素。什么 病毒蛋白是由CD4和CD8T细胞识别的，它们是如何识别的 细胞相互作用？Fas通路与疾病有关吗？2. 探讨抗体和T细胞在控制CVB3中的作用 感染和疾病。哪些病毒蛋白可以预防CVB？ 启动CD8 T细胞免疫是有益的还是有害的？ 确定在急性和持续性CVB3感染期间感染的细胞。 柯萨奇B细胞病毒在感染早期是否与B细胞相互作用？其他细胞是什么？ 感染了吗？在病毒持续期间感染了哪些细胞？4. 开始评估持续性CVB3的性质。我们已经开发出 一种系统，在该系统中，持续感染的老鼠含有高水平的 传染性病毒。这种持续存在的病毒与最初的病毒有什么不同？ 5.评价CVB3持续感染的治疗方法。抗体- 缺陷人类经常遭受慢性小核糖核酸病毒感染， 这些疾病往往难以治疗。我们的小鼠模型 在没有B细胞的情况下，持久性将用于测试不同的 治疗方案。

Coxsackieviruses, members of the picornavirus family, are important human pathogens. Coxsackievirus B3 (CVB3), is a common associated factor in human subacute, acute, and chronic myocarditis. In young adults CVB3 infections may cause cardiac arrhythmias and acute heart failure; and chronic disease may supervene, leading to dilated cardiomyopathy, requiring transplantation, or to death. To better understand the pathogenesis of this disease, several mouse model systems have been established, which appear to parallel many aspects of the human disease process. We have begun to investigate the mechanisms underlying CVB myocarditis. The goals of this proposal are: 1. To further investigate the immune determinants of CVB3 myocarditis. What viral proteins do CD4+ and CD8+ T cells recognize, and how do these cells interact? Is the Fas pathway involved in disease? 2. To investigate the roles of antibodies and T cells in control of CVB3 infection and disease. Which virus proteins can protect against CVB? Is priming of CD8+ T-cell immunity beneficial or harmful? 3. To determine the cells infected during acute and persistent CVB3 infection. Does CVB interact with B cells early in infection? What other cells are infected? What cells are infected during virus persistence? 4. To begin evaluation of the nature of persistent CVB3. We have developed a system in which persistently-infected mice contain high levels of infectious virus. Does this persisting virus differ from the original? 5. To evaluate treatments for persistent CVB3 infection. Antibody- deficient humans often suffer from chronic picornavirus infections, which are frequently refractory to treatment. Our mouse model of persistence in the absence of B cells will be used for testing different treatment regimens.