DEVELOPMENT OF RESPIRATORY VIRUS INFECTION STRATEGIES FOR RHESUS MACAQUE AIRWAYS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们的主要目标是了解呼吸道病毒感染在人类哮喘和慢性呼吸道炎症恶化的病因中所起的致病作用。我们的次要目标是开发有效和安全的疫苗方法来预防幼儿呼吸道合胞病毒感染。我们认为，肺部呼吸道病毒病理生物学的基本免疫和生理机制只能通过活体动物感染模型来阐明。虽然已经建立了呼吸道病毒感染的啮齿动物模型，但该物种并不能有效地复制灵长类动物出生后肺部和免疫系统的发育。我们的目标是利用恒河猴(Macaca Mulatta)建立人类呼吸道合胞病毒和人鼻病毒感染的实验动物模型。为此，第一步是优化恒河猴对人类呼吸道病毒感染的易感性。我们推测，要建立一个显示人类临床症状的呼吸道感染模型，将需要人类病毒分离株在恒河猴细胞中体外传代，以获得在猴子呼吸道中强大的病毒复制能力。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our primary objective is to understand the pathogenic role of respiratory virus infection in the etiology of asthma and exacerbation of chronic airways inflammation in humans. Our secondary objective is to develop effective and safe vaccine approaches to prevent respiratory syncytial virus infection in young children. We propose that basic immune and physiologic mechanisms for respiratory virus pathobiology in the lung can only be elucidated using an in vivo animal model of infection. Although rodent models have been developed for respiratory virus infection, this species does not effectively duplicate the postnatal development of both lung and immune systems in primates. Our goal is to develop an experimental animal model of human respiratory syncytial virus and human rhinovirus infection using the rhesus macaque monkey (Macaca mulatta). Towards this end, the first step is to optimize the susceptibility of rhesus monkeys to human respiratory virus infection. We hypothesize that the development of a respiratory infection model that demonstrates human clinical symptoms will require in vitro passaging of human viral isolates in rhesus cells to obtain robust viral replication in monkey airways.