IMMUNOLOGICAL RESPONSE TO PRIMARY & SECONDARY INFLUENZA INFECTION IN NH PRIMATES

这个子项目是许多研究子项目中的一个 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来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 流感病毒每年感染10%至20%的美国人口，导致约36，000人死亡。在偶尔发生的大流行期间，感染率和死亡率会急剧上升，其中三次发生在过去90年中。人们越来越担心，下一次大流行可能来自高致病性禽流感病毒，在病毒从受感染的鸟类传播给人类的情况下，死亡率超过50%。因此，功能基因组学和传染病部门的研究人员正在使用非人灵长类动物感染模型来定义流感病毒-宿主相互作用以及对感染的先天性和适应性免疫反应。该项目的目标是提供可能导致新的抗病毒疗法或改进的疫苗接种策略的信息。使用非人灵长类动物模型的初步研究将集中在宿主对A/Yokohama/2017/03（H3 N2）的反应，A/Yokohama/2017/03（H3 N2）是最近的季节性人类流感分离株。这些研究的一个重要组成部分将是对从受感染动物的血液和淋巴结中分离的特定细胞类型进行详细分析。在本报告期内进行的实验集中于建立通过流式细胞术分选细胞的技术和参数，以及优化从分离的细胞中收获RNA和蛋白质的时间和方法，用于随后分析细胞基因表达和蛋白质丰度谱。掌握这些信息后，将在初始研究中使用两组动物;一组用于评价对原发性感染的反应，第二组用于评价对42天后开始的继发性感染的反应。该策略将提供关于先天免疫应答的分子机制以及先前暴露于病毒所提供的保护（适应性免疫）的特征和程度的信息。

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. Influenza virus infects from 10 to 20% of the U.S. population annually, resulting in the death of approximately 36,000 people. Infection and mortality rates can rise dramatically during occasional pandemics, three of which have occurred over the last 90 years. There is growing concern that the next pandemic could arise from highly pathogenic avian influenza viruses, which have a mortality rate of over 50% in cases where the virus has been transmitted from infected birds to humans. Investigators in the Division of Functional Genomics and Infectious Disease are therefore using a nonhuman primate infection model to define influenza virus-host interactions and the innate and adaptive immune responses to infection. The goal of this project is to provide information that may lead to new antiviral therapies or improved vaccination strategies. Initial studies using the nonhuman primate model will focus on the host response to A/Yokohama/2017/03 (H3N2), a recent seasonal isolate of human influenza. An important component of these studies will be the detailed analysis of specific cell types isolated from the blood and lymph nodes of infected animals. Experiments performed during the current reporting period have focused on establishing the techniques and parameters for sorting cells by flow cytometry and for optimizing the timing and methods for harvesting RNA and protein from isolated cells for subsequent analysis of cellular gene expression and protein abundance profiles. With this information in hand, two groups of animals will be used in initial studies; one group to evaluate the response to a primary infection, and a second group to evaluate the response to a secondary infection initiated 42 days later. This strategy will provide information regarding the molecular mechanisms underlying innate immune responses and the character and degree of protection (adaptive immunity) provided by previous exposure to the virus.