NEUTRALIZATION OF RESRIRATORY VIRUS AT THE AIRWAY MUCOSA

在呼吸道，对呼吸道病毒感染的抵抗力最强 与病毒特异性IgA抗体的存在有关 粘膜分泌物。免疫球蛋白A通过上皮衬里运输 由多聚免疫球蛋白受体引起的粘膜细胞 (PIG-R)在分泌之前。此外，呼吸道病毒可以复制 在这些细胞内。因此，IgA可能与新的 在细胞内合成病毒蛋白，有效地流产病毒 病毒排出前的感染。这项提议的重点是 通过描绘这部小说和之前的故事来探索这个假设 未知的免疫球蛋白A中和粘膜病毒的机制 浮出水面。已勾勒出四个具体目标。最初，使用IgA 针对病毒结构蛋白的单抗，有能力 阻断仙台和流感病毒复制的IgA将是 在Madin-Darby犬肾脏上皮细胞中进行检测 将CDNA导入兔Pig-R。其次，既是最优的 IgA的抗原特异性及其对病毒的最敏感步骤 细胞内中和的繁殖将被确定。 第三，由于仙台和流感病毒有不同的细胞模式 进入和复制，IgA可以很容易地中断他们的 将对各自的生命周期进行比较。最后，为了更好地复制 自然生物环境下的大鼠气管上皮细胞系 将其与大鼠PIG-R的cDNA一起转染，并随后用作 一种研究IgA与病毒细胞内相互作用的模型。这个 这些研究的结果将被用于设计未来的实验， 将检查和比较病毒的组织病理学后果 在存在抗病毒药物的情况下上皮细胞系统的感染 不同类别的抗体和抗原特异性。信息 这些研究产生的数据可能有助于SAFE的发展， 有效的抗病毒免疫方案和新的方法 病毒呼吸道感染后遗症的医疗管理， 包括呼吸道反应性增强。

In the airway, resistance to respiratory viral infections best correlates with the presence of viral specific IgA antibodies in the mucosal secretions. IgA is transported through the epithelial lining cells of a mucous membrane by the polymeric immunoglobulin receptor (Pig-R) prior to secretion. Moreover, respiratory viruses replicate within these cells. Therefore, IgA may be able to complex with newly synthetized viral proteins within cells, effectively abort viral infection prior to viral shedding. The focus of this proposal is to explore this hypothesis by delineating this novel and previously undescribed mechanism by which IgA can neutralize virus at a mucosal surface. Four specific aims have been outlined. Initially, using IgA monoclonal antibodies against the viral structural proteins, the ability of IgA to interrupt replication of Sendai and Influenza viruses will be examined in Madin-Darby Canine Kidney epithelial cells which have been transfected with the CDNA for rabbit Pig-R. Secondly, both the optimal antigenic specificity of IgA and the most susceptible step in virus reproduction for intracellular neutralization will be determined. Thirdly, since Sendai and Influenza viruses have different modes of cell entry and replication, the ease with which IgA can interrupt their respective life cycles will be compared. Finally, to better replicate the natural biological environment, a rat tracheal epithelial cell line will be transfected with the cDNA for rat pIg-R and subsequently used as a model to study intracellular interaction between IgA and virus. The results of these studies will be used to design future experiments which will examine and compare the histopathological consequences of viral infection in an epithelial cell system in the presence of anti-viral antibodies of different classes and antigenic specificity. Information generated by these studies could contribute to the development of safe, effective anti-viral immunization protocols and to new approaches to the medical management of the sequelae of viral respiratory infections, including heightened airway reactivity.