Coxsackie Myocarditis and Viral Persistence in the Heart

超出所提供的空间。柯萨奇病毒（CVB）是重要的人类病原体，可引起心肌炎、脑膜炎和其他可能致命的疾病，特别是在新生儿中。该提案有五个具体目标，重点关注CVB的发病机制（aims 1-3）和免疫（aims 4, 5）。目的1。CVB在体内是否优先感染增殖细胞？我们已经在组织培养中证明，细胞周期对CVB基因表达和病毒产生有显著影响。在体内，在心脏、中枢神经系统或免疫系统中也是如此吗？我们将识别这些组织中的增殖细胞，并确定它们是否更容易受到感染。如果心脏在体内受损，这是否会改变其对随后CVB感染的易感性？目标2。病毒的哪个部分对宿主细胞周期有反应？接下来，我们将研究等式的病毒方面。我们假设内部核糖体进入位点可能是病毒的“反应元件”；这将在组织培养和体内进行评估。目标3。提出的CVB受体在心脏和中枢神经系统的向性和发病机制中起什么作用？我们将评估受体的表达水平。它们会随着年龄的增长而变化吗？感染/组织损伤后，邻近细胞中的受体是否上调？目标4。CD8 - T细胞如何参与CVB感染的控制？我们已经证明，在CVB感染期间，CD8 - T细胞可以降低病毒滴度，并且这种作用不需要穿孔素。抗病毒作用涉及哪些效应功能？这些效应功能会导致组织损伤吗？目标5。CVB是如何如此有效地避免诱导强烈的CD8 - T细胞反应的？大多数病毒感染诱导高水平的抗病毒CD8 + rl"细胞。CVB是如何避免这种情况的呢？我们能改变这种状况吗？网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. Coxsackieviruses (CVB) are important human pathogens, causing myocarditis, meningitis, and other diseases which may be lethal, especially in neonates. This proposal has five specific aims focused on CVB pathogenesis (Aims 1-3) and immunity (Aims 4, 5). Aim 1. Does CVB preferentially infect proliferating cells in vivo? We have shown, in tissue culture, that the cell cycle exerts a dramatic effect on CVB gene expression & virus production. Is this also true in vivo, in the heart, central nervous system, or immune system? We shall identify proliferating cells in these tissues, and will determine if they are more susceptible to infection. If the heart is injured in vivo, does this alter its susceptibility to subsequent CVB infection? Aim 2. What component of the virus responds to the host cell cycle? Next, we shall study the viral side of the equation. We hypothesize that the internal ribosome entry site may be the viral "response element"; this will be evaluated in tissue culture, and in vivo. Aim 3. What role do the proposed CVB receptors play in tropism & pathogenesis in the heart & CNS? We shall evaluate the expression levels of the receptors. Do they change with age? Following infection / tissue damage, are the receptors upregulated in neighboring cells? Aim 4. How do CD8 ¿ T cells contribute to the control of CVB infection ? We have shown that, during CVB infection, CD8 ¿ T cells can reduce viral titers, and that this effect does not require perforin. What effector functions are involved in the antiviral effect? Do these effector functions contribute to tissue damage? Aim 5. How does CVB so effectively avoid inducing strong CD8 ¿ T cell responses? Most virus infections induce high levels of antiviral CD8 + rl"cells. How does CVB avoid this? Can we rectify the situation? PERFORMANCE SITE ========================================Section End===========================================