NEUTRALIZATION OF RESPIRATORY VIRUS AT THE AIRWAY MUCOSA

在呼吸道中，抵抗呼吸道病毒感染的能力最好 相关的病毒特异性伊加抗体的存在， 粘膜分泌物。伊加是通过上皮内层运输的 多聚免疫球蛋白受体对粘膜细胞的作用 （猪-R）分泌前。此外，呼吸道病毒复制 在这些细胞中。因此，伊加可能能够与新的 在细胞内合成病毒蛋白，有效地中止病毒 在病毒脱落之前感染。本提案的重点是 通过描绘这部小说和以前的 伊加可以在粘膜中中和病毒的一种未知机制， 面提出了四个具体目标。最初，使用伊加 针对病毒结构蛋白的单克隆抗体， 的伊加中断仙台和流感病毒的复制， 在Madin-Darby犬肾上皮细胞中检查， 用兔Pig-R的cDNA转染。第二，最优 伊加的抗原特异性和病毒中最敏感的步骤 将确定用于细胞内中和的繁殖。 第三，由于仙台病毒和流感病毒具有不同的细胞模式， 进入和复制，与伊加可以中断他们的容易， 将比较各自的生命周期。最后，为了更好地复制 自然生物环境下，大鼠气管上皮细胞系 将用大鼠pIg-R的cDNA转染，随后用作 研究伊加与病毒细胞内相互作用的模型。的 这些研究的结果将用于设计未来的实验， 将检查和比较病毒感染的组织病理学后果， 在抗病毒药物存在下上皮细胞系统中的感染 不同种类的抗体和抗原特异性。信息 这些研究所产生的结果可能有助于开发安全， 有效的抗病毒免疫方案和新的方法， 病毒性呼吸道感染后遗症的医疗管理， 包括气道反应性增强。

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.