NEUTRALIZATION OF RESRIRATORY VIRUS AT THE AIRWAY MUCOSA

中和呼吸道粘膜的呼吸道病毒

• 批准号: 3456112
• 负责人: MARY B MAZANEC
• 金额: $ 10.57万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-01 至 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3456112
• 关键词: MDCK cell; SDS polyacrylamide gel electrophoresis; allergic pneumonitis; antibody receptor; antiviral agents; antiviral antibody; biological models; complementary DNA; enzyme linked immunosorbent assay; immunoglobulin A; kidney cell; laboratory mouse; model design /development; monoclonal antibody; neutralizing antibody; parainfluenza virus type 1; respiratory epithelium; respiratory infections; secretory immune system; transfection; virus cytopathogenic effect; virus protein; virus replication

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.

在气道中，抵抗呼吸道病毒感染的能力最好 与病毒特异性 IgA 抗体的存在相关 粘膜分泌物。 IgA 通过上皮层运输 粘膜细胞通过聚合免疫球蛋白受体 (Pig-R) 分泌前。此外，呼吸道病毒会复制 在这些细胞内。因此，IgA 可能能够与新的复合物 在细胞内合成病毒蛋白，有效中止病毒 病毒脱落前的感染。该提案的重点是 通过描述这本小说和以前的小说来探索这个假设 IgA 可在粘膜中和病毒的未描述机制 表面。概述了四个具体目标。最初，使用 IgA 针对病毒结构蛋白的单克隆抗体，能够 IgA 可以中断仙台病毒和流感病毒的复制 在 Madin-Darby 犬肾上皮细胞中进行了检查，这些细胞已被 用兔 Pig-R 的 cDNA 转染。其次，无论是最优 IgA的抗原特异性和病毒最易受影响的步骤 将确定细胞内中和的繁殖。 第三，由于仙台病毒和流感病毒具有不同的细胞模式 IgA 可以轻松地中断其进入和复制 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，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 IgA 和病毒之间细胞内相互作用的模型。这 这些研究的结果将用于设计未来的实验 将检查并比较病毒的组织病理学后果 抗病毒药物存在下上皮细胞系统的感染 不同类别和抗原特异性的抗体。信息 这些研究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。