Immune signatures of clinical responses to flavivirus infections

免疫状态和功能的个体差异决定了对感染的反应， 疾病的严重程度和结果。在这个建议中，我们将采用高通量的最新进展， 描述个体免疫应答的技术，以识别定义个体的分子特征， 对黄病毒感染的免疫反应。我们将研究患者的免疫反应， 使用西尼罗河病毒（WNV）（通常为短暂感染）和丙型肝炎作为模型的分层队列 病毒（HCV），可以是短暂的，伴有正在消退的病毒血症，或慢性的，伴有持续的病毒血症，导致 肝硬化和死亡使用高灵敏度的多维细胞流式细胞术， 分析，并与临床病史的相关性，我们将提供细胞机制的分子概况， 原代人类免疫细胞目标1和2的概况分析研究将构成建模和 预测网络和关键的细胞通路，以确定关键的效应器和调控机制， 抗黄病毒感染（见研究项目3）。这些预测将通过 在原代细胞中进行详细检查，以证明所鉴定组分的作用。

Individual variations in immune status and function determine responses to infection and contribute to disease severity and outcome. In this proposal, we will employ recent advances in high-throughput technology to profile individual immune responses to identify the molecular signatures defining individual immune responses to flaviviral infections. We will investigate the immune responses of patients from stratified cohorts using as models West Nile virus (WNV), generally a transient infection, and hepatitis C virus (HCV), which can be transient with a resolving viremia, or chronic with a persistent viremia leading to cirrhosis and death. Using highly sensitive multidimensional cell flow cytometry, multiplexed gene expression analysis, and correlation with clinical history, we will provide molecular profiles of cellular mechanisms of primary human immune cells. The profiling studies of Aims 1 and 2 will form the basis for modeling and predictions of networks and critical cellular pathways to identify key effectors and regulatory mechanisms of resistance to flaviviral infections (see Research Project 3). These predictions will be validated through detailed examination in primary cells to demonstrate the role of identified components.