DEVELOPMENT OF RESPIRATORY VIRUS INFECTION STRATEGIES FOR RHESUS MACAQUE AIRWAYS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 我们的主要目的是了解呼吸道病毒感染在人类哮喘病因学和慢性气道炎症加重中的致病作用。我们的第二个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，呼吸道病毒在肺部的病理生物学的基本免疫和生理机制只能通过体内动物感染模型来阐明。尽管已经开发了呼吸道病毒感染的啮齿动物模型，但该物种不能有效地复制灵长类动物的肺和免疫系统的出生后发育。我们的目标是建立一个实验动物模型，人呼吸道合胞病毒和人鼻病毒感染恒河猴（Macaca mulatta）。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。我们假设，开发一个呼吸道感染模型，证明人类的临床症状，将需要在恒河猴细胞中体外传代的人病毒分离株，以获得强大的病毒复制在猴气道。

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.