MOLECULAR BASIS OF PERSISTENT VIRUS INFECTION

病毒感染往往会导致致病后果和 疾病大大超过了感染的急性期。这个 持续性感染对人类疾病进程的意义 现在才变得明显起来。在坚持不懈的过程中 感染，疾病可能是宿主免疫的结果 对病毒和病毒感染细胞和/或来自 病毒对细胞功能的破坏。目前，只有 对持久性病毒分子细节的了解有限 感染。 有很多建议认为缺陷干扰(DI) RNAs可能参与建立和维持 持续的病毒感染。尽管DI RNAs已链接到 在组织培养系统中持续存在的信息很少 这与DI RNAs的外观和功能直接相关 在体内感染期间。这里提出的研究将检查 淋巴细胞诱导的实验小鼠持续性感染 脉络膜脑膜炎病毒以确定是否删除了RNA(即， 潜在的DI RNAs)出现并持续积累 感染的动物以及这些RNA是否改变了正常的过程 急性感染。一系列互补的实验将 研究减少病毒传播的潜在调控机制 基因表达，并可能介导从急性到 持续性感染。 对病毒分子基础的详细了解 在一个系统中的持久化将允许对 病毒持久性的整个领域，并可能为 持续感染的干预和最终清除。

Virus infections often lead to pathogenic consequences and disease considerably beyond the acute phase on infection. The significance of persistent infections for human disease processes is only now becoming apparent. In the course of a persistent infection, disease may develop as a consequence of host immune responses against the virus and virus infected cells and/or from virus disruption of cellular functions. At present, there is only limited understanding of the molecular details of persistent virus infection. There have been many suggestions that defective interfering (DI) RNAs may be involved with the establishment and maintenance of persistent virus infections. Although DI RNAs have been linked to persistence in tissue culture systems, there is little information that relates directly to the appearance and function of DI RNAs during infection in vivo. The studies proposed here will examine persistent infections induced in laboratory mice by lymphocytic choriomeningitis virus to determine whether deleted RNAs (i.e., potential DI RNAs) appear and accumulate in persistently infected animals and whether these RNAs alter the normal course of acute infection. A complementary series of experiments will investigate potential regulatory mechanisms that reduce viral gene expression and may mediate the transition from acute to persistence infection. A detailed understanding of 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.