Transgenic Mouse Model for the Common Cold

描述（由申请方提供）：病毒性呼吸道感染是全球所有年龄段个体急性发病的最常见原因。在高峰期，小核糖核酸病毒单独导致约80%的急性呼吸道感染，并且是限制活动和医生咨询的主要原因。尽管小核糖核酸病毒引起的普通感冒通常是良性的，但它是严重呼吸系统疾病急性加重的罪魁祸首，例如支气管哮喘或慢性阻塞性肺病。原发性小核糖核酸病毒呼吸道感染或继发性肺部疾病加重的机制尚未完全清楚。此外，没有特异性抗病毒化疗可用。在致病机制研究和抗病毒药物开发方面取得进展的一个主要障碍是缺乏用于普通感冒的实用动物模型。一般来说，发病机制和药理学试验的研究依赖于故意感染志愿者。我们产生的小鼠转基因的人细胞间粘附分子-1（hICAM-1）基因，表现出hICAM-1在呼吸道上皮细胞的表达类似于人类。这些小鼠原则上易受绝大多数小核糖核酸病毒的感染，这些病毒将hICAM-1识别为细胞受体。本项目旨在通过产生具有呼吸道嗜性的小核糖核酸病毒来建立普通感冒的小鼠模型，该病毒能够在hICAM-1转基因小鼠的呼吸道中繁殖并引发特征性病变和宿主反应。我们的研究旨在为普通感冒建立一个实用的小动物模型，这是全球肺部疾病和相关医疗保健支出的主要原因。这种疾病模型将提供更好的机会来阐明病毒性呼吸道感染的机制，并测试新的治疗方法，使潜在肺部疾病加重风险的患者受益。

DESCRIPTION (provided by applicant): Viral respiratory tract infections are the most common cause of acute morbidity in individuals of all ages worldwide. Picornaviruses alone are responsible for ~80% of all acute respiratory infections during peak season and are a major cause for restricted activity and physician consultation. Despite the generally benign course of the common cold caused by picornaviruses, it is the main culprit for acute exacerbation of serious respiratory system disorders, for example bronchial asthma or chronic obstructive pulmonary disease. The mechanisms of primary picornaviral respiratory tract infection or secondary exacerbation of pulmonary disease are not fully understood. Moreover, no specific anti-viral chemotherapy is available. A major impediment to advances in research of pathogenic mechanisms and anti-viral drug development is the absence of a practical animal model for the common cold. Generally, studies of pathogenesis and pharmacologic testing rely on deliberate infection of volunteers. We generated mice transgenic for the human intercellular adhesion molecule-1 (hICAM-1) gene, which exhibit hICAM-1 expression in respiratory epithelium similar to humans. These mice in principle are susceptible to infection with the vast majority of picornaviruses, which recognize hICAM-1 as a cellular receptor. This project aims to establish a murine model for the common cold by generating picornaviruses with respiratory tropism capable of propagating and eliciting characteristic lesions and host responses in the respiratory tract of hICAM-1 transgenic mice. Our research intends to generate a practical small animal model for the common cold, a major cause for pulmonary illness and associated health care expenditure worldwide. This disease model would provide far improved opportunities to unravel mechanisms of viral respiratory tract infection and to test new therapeutic approaches benefiting patients at risk from exacerbation of underlying pulmonary disease.