Deer Mice as Immunological Tools for Infectious Disease

描述（由申请人提供）：汉坦病毒心肺综合征（HCPS）是一种以感染患者肺部存在炎性细胞因子生成T细胞为特征的新兴传染病。北美的大多数HCPS病例是由Sin Nombre病毒（SNV）引起的，尽管已知有十多种其他汉坦病毒在北美和南美引起HCPS。无论病毒病因如何，在感染的毛细血管内皮细胞中几乎没有观察到细胞病变效应，表明该疾病是细胞因子介导的免疫病理。相比之下，SNV的天然宿主鹿鼠（Peromyscus maniculatus）在感染后没有表现出任何病理，并且可能是终生的持续携带者。虽然他们的肺部含有复制病毒，但没有观察到肺部炎症，这表明免疫系统已经进化出一种非致病性应答。目前尚不清楚鹿鼠是如何感染SNV的。我们已经启动了一项研究计划，开发分子和细胞分析，以检测鹿小鼠的免疫功能和细胞因子反应。这些技术将用于阐明鹿小鼠持续感染sinnombre病毒（SNV）的机制。我们已经开发了从远交种鹿小鼠中长期培养T细胞系的方法，目前正在努力从19只实验感染的鹿小鼠中建立T细胞系。这些细胞系将通过实时PCR检测其细胞因子谱，以确定其免疫表型（即Th1， Th2, Treg）。我们还将检测自然感染SNV的野鹿小鼠的T细胞反应，以确定自然感染是否与实验感染相似。确定鹿鼠控制感染的策略可以为HCPS的临床管理提供见解。

DESCRIPTION (provided by applicant): Hantavirus cardiopulmonary syndrome (HCPS) is an emerging infectious disease characterized by the presence of inflammatory cytokine-producing T cells in the lungs of infected patients. Most cases of HCPS in North America are caused by Sin Nombre virus (SNV), although more than a dozen other hantaviruses are known to cause HCPS in North and South America. Regardless of the viral etiology, virtually no cytopathic effect is observed in infected capillary endothelial cells, indicating that the disease is a cytokine-mediated immunopathology. In contrast, deer mice (Peromyscus maniculatus), the natural host of SNV, exhibit no pathology when infected and remain persistent carriers, perhaps for life. Although their lungs contain replicating virus, no pulmonary inflammation is observed, indicating that the immune system has evolved a nonpathogenic response for containing SNV. It is unknown how deer mice engage SNV. We have initiated a research program to develop molecular and cellular assays to detect immune functions and cytokine responses in deer mice. These techniques will be used to elucidate the mechanisms of persistent infection of Sin Nombre virus (SNV) in deer mice. We have developed the methods for long-term culturing of T cell lines from outbred deer mice and are currently working to establish lines from 19 experimentally-infected deer mice. These lines will be examined for their cytokine profiles by real-time PCR to determining their immunological phenotypes (i.e., Th1, Th2, Treg). We will also examine the T cell responses in wild deer mice naturally-infected with SNV to determine if natural infection parallels that of experimental infection. Identification of the strategies employed by deer mice to contain infection without pathology could provide insight into the clinical management of HCPS.