CARDIAC MUSCLE DISEASE AND ENTEROVIRUS PRESENCE

心肌疾病和肠道病毒的存在

• 批准号: 3357397
• 负责人: STEVEN M TRACY
• 金额: $ 7.78万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3357397
• 关键词: Coxsackievirus; chronic disease /disorder; disease /disorder model; genetic enhancer element; genome; in situ hybridization; laboratory mouse; myocarditis; myocardium; myocardium disorder; natural gene amplification; nucleic acid hybridization; nucleic acid probes; nucleic acid sequence; oligonucleotides; virus RNA; virus classification; virus cytopathogenic effect; virus genetics

The long-term goal of the proposed research is to correlate enteroviral presence in the heart, and perhaps other organs, with causation of acute myocarditis which progresses to chronic myocardial diseases such as dilated cardiomyopathies. The two specific aims of the work are (1) to examine the role of the inducing coxsackievirus B3 and murine genetic backgrounds through in situ hybridization detection of viral RNA in many murine tissues during disease progression following viral innoculation; (2) to sensitively probe human heart tissue and peripheral blood mononuclear cells of clinically well- characterized myocarditis patients and myocardium of explanted dilated hearts for the presence of enteroviral genomes and to develop a rapid, sensitive assay for enteroviral RNA using enzymatic amplication of nucleotide sequences and novel enhanced rate hybridization kinetics capable of detecting in the range of 10-100 enteroviral RNa molecules in biopsy within hours. The mouse model will be employed to determine what effects the virulence of the virus and the host genetic background have on viral persistence, disease progression, and presence of virus in the chronic phase of the disease and to draw inferences to the presumed homologous human situation. These experiments will provide essential data to evaluate whether enteroviruses remain in tissues other than heart following acute infection, perhaps acting as seeds to promote the inflammatory processes which have been demonstrated as deleterious to the heart in chronic disease. Screening of human hearts for enteroviral RNA, by in situ hybridization and later using a more sensitive approach developed in the course of this work, will determine whether enteroviral presence and presence of pathologic changes in the affected human organ can be correlated. Cumulatively, these experiments will determine whether there is justification to pursue prophylactic measures against specific enteroviruses as causes of human myocarditis and cardiomyopathies.

拟议研究的长期目标是关联 肠病毒在心脏，也许还有其他器官， 急性心肌炎的因果关系发展为慢性 心肌疾病，例如扩张的心肌病。 两个 工作的具体目的是（1）检查 诱导Coxsackievivirus B3和鼠遗传背景 通过原位杂交检测病毒RNA 病毒后疾病进展过程中的鼠组织 in依（2）敏感探测人类心脏组织和 临床上良好的外周血单核细胞 表征心肌炎患者和外植体的心肌 肠道病毒基因组存在的心脏扩张和 使用使用肠病毒RNA的快速，敏感的测定 核苷酸序列和新型的酶促扩增 增强速率杂交动力学能够检测 几个小时内活检中的10-100个肠病毒RNA分子的范围。 将采用鼠标模型来确定什么影响 病毒和宿主遗传背景的毒力在 病毒持久性，疾病进展和病毒的存在 疾病的慢性阶段，并提出推断 假定的同源人类状况。 这些实验会 提供基本数据来评估肠病毒是否保留 在急性感染后心脏以外的组织中，也许 充当种子来促进炎症过程 在慢性中被证明是对心脏有害的 疾病。 通过筛查人类心脏的肠病毒RNA，in 原位杂交，然后使用更敏感的方法 在这项工作过程中开发的，将确定是否 肠病毒的存在和病理学的存在 受影响的人体器官可以关联。 累计，这些 实验将确定是否有合理 采取针对特定肠病毒的预防措施 人心肌和心肌病的原因。