MOLECULAR BASIS OF PERSISTENT VIRUS INFECTION

持续病毒感染的分子基础

• 批准号: 3138620
• 负责人: PETER J SOUTHERN
• 金额: $ 16.63万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3138620
• 关键词: DNA directed RNA polymerase; disease /disorder model; gel electrophoresis; gene expression; genetic manipulation; immunoregulation; laboratory mouse; lymphocytic choriomeningitis; molecular pathology; nucleic acid hybridization; nucleic acid probes; tissue /cell culture; virulence; virus RNA; virus cytopathogenic effect; virus infection mechanism; virus protein

As detection methods become more sophisticated, there is an increasing realization that viruses can reside within apparently normal hosts for extended periods. During such long-term infections, virus reactivation may occur spontaneously or after changes in the immunological status of the host. The onset of virus replication may initiate pathogenic events by provoking immune responses against the virus and virus infected cells and/or from virus disruption of cellular functions. The significance of long-term infections for human disease processes is only now becoming fully apparent and there have been several suggestions that viruses may be involved with chronic degenerative diseases. At present, there is only limited understanding of the molecular events associated with the establishment and maintenance of long-term virus infections both with respect to alterations in virus gene expression and virus-induced changes within the infected individual. I intend to study a well-characterized and reproducible model system, based on persistent infections of laboratory mice and tissue culture cells with lymphocytic choriomeningitis virus, to identify regulatory events that mediate the transition from acute to persistent infection and subsequent maintenance of the persistent infection. A detailed explanation for the molecular basis of virus persistence in one system will allow conceptual developments for the whole field of virus persistence and may suggest strategies for intervention and eventual clearance of a persistent infection.

随着检测方法变得越来越复杂， 意识到病毒可以驻留在表面上正常的宿主中， 延长期限。 在这种长期感染期间，病毒的重新激活可能 自发发生或在免疫状态发生变化后， 主持人 病毒复制的开始可通过以下方式启动致病事件： 激发针对病毒和病毒感染细胞的免疫应答 和/或来自病毒破坏细胞功能。 的意义 人类疾病过程的长期感染现在才完全 显然，有几个建议，病毒可能是 与慢性退行性疾病有关 目前只有 有限的了解分子事件与 建立和维持长期病毒感染， 关于病毒基因表达的改变和病毒诱导的变化 在受感染的个体中。 我打算研究一个特点鲜明， 可重复的模型系统，基于实验室持续感染 小鼠和组织培养细胞与淋巴细胞性脉络丛脑膜炎病毒， 确定调节事件，介导从急性到 持续性感染和随后的持续性维持 感染 病毒分子基础详解 在一个系统中的持久性将允许整体的概念发展 病毒持续存在的领域，并可能提出干预策略， 最终清除持续性感染。