MOLECULAR BASIS OF PERSISTENT VIRUS INFECTION

持续病毒感染的分子基础

• 批准号: 3138625
• 负责人: PETER J SOUTHERN
• 金额: $ 20.43万
• 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 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3138625
• 关键词: DNA directed RNA polymerase; chromosome aberrations; disease /disorder model; gel electrophoresis; gene expression; genetic manipulation; host organism interaction; 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.

随着检测手段的日益完善，检测手段也越来越多 认识到病毒可以在表面上正常的宿主体内驻留 延长的时间。 在这种长期感染过程中，病毒可能会重新激活 自发发生或在免疫状态改变后发生 主持人。 病毒复制的开始可能通过以下方式引发致病事件： 激发针对病毒和病毒感染细胞的免疫反应 和/或病毒破坏细胞功能。 意义 人类疾病过程的长期感染现在才变得完全 很明显，并且有一些建议表明病毒可能是 与慢性退行性疾病有关。 目前，只有 对与此相关的分子事件的了解有限 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 在感染者体内。 我打算学习一个有特色且 可重复的模型系统，基于实验室持续感染 小鼠和带有淋巴细胞脉络膜脑膜炎病毒的组织培养细胞， 确定介导从急性到急性的转变的监管事件 持续感染和随后持续的维持 感染。 病毒分子基础的详细解释 坚持一个系统将有助于整体概念的发展 病毒持久性领域，并可能提出干预策略和 最终清除持续感染。