Respiratory Syncytial Virus Targeting of the Human Airway Epithelium

摘要： 呼吸道合胞病毒(RSV)是婴幼儿住院的最常见原因， 但目前还没有疫苗或抗病毒药物可用。RSV感染鼻腔、气管和更小的细胞 航空公司。该实验室的总体目标是了解RSV如何感染其目标细胞纤毛呼吸道。 细胞，并利用这些信息来开发更好的疫苗和抗病毒药物候选。这个实验室使用 原代分化良好的人呼吸道上皮细胞(HAECs)用于研究呼吸道合胞病毒感染。这些HAEC有 最近被用来鉴定纤毛呼吸道细胞上的一个重要的RSV受体。提供的初步数据 证明这些HAEC产生的RSV对HAEC的传染性比对HAEC的传染性大得多 永生化细胞及其附着、G、糖蛋白是造成这种差异的原因。G蛋白被修饰 在HAEC中不同的是，当它穿过细胞时，在它被合并到RSV病毒粒子的过程中 质膜和这种修饰可能是其活性增强的原因。该项目将确定 修饰和制造它的机制。RSV还会产生一种分泌型的G蛋白 这会触发免疫细胞向RSV感染的细胞迁移。该项目还将确定这一秘密是否 G蛋白像全长版本一样被修饰，如果它的信号活性被其改变或增强 修饰，类似于全长G蛋白。一旦G蛋白和分泌的G蛋白的修饰 以及修改它们的机制被标识，则该信息可以使 生产更有效、更经济的RSV减毒活疫苗并为新的靶点提供靶点 抗病毒药物。该项目将推进美国国立卫生研究院发展基础知识延伸的使命 健康的生活，减轻疾病的负担。

Abstract: Respiratory syncytial virus (RSV) is the most frequent cause of hospitalization for infants and young children, but no vaccines or antiviral drugs are yet available. RSV infects the cells that line the nose, trachea and smaller airways. The overall goal of the laboratory is to understand how RSV infects its target cell, the ciliated airway cell, and to use that information to develop better vaccine and antiviral drug candidates. This laboratory uses primary well differentiated human airway epithelial cultures (HAECs) to study RSV infection. These HAECs have recently been used to identify an important RSV receptor on the ciliated airway cells. Preliminary data presented here demonstrate that the RSV produced by these HAECs is much more infectious for HAECs than for immortalized cells and its attachment, G, glycoprotein is responsible for this difference. The G protein is modified differently in HAECs as it passes through the cell, on its way to being incorporated into the RSV virion at the plasma membrane and this modification may be responsible for its enhanced activity. This project will identify the modification and the mechanism by which it is made. RSV also produces a secreted form of the G protein that triggers immune cells to migrate toward RSV-infected cells. This project will also determine if this secreted G protein is modified like the full-length version, and if its signaling activity is changed or enhanced by its modification, similar to the full-length G protein. Once the modification of the G protein and the secreted G protein are identified, and the mechanism by which they are modified are identified, this information could enable the production of more effective and economical live attenuated vaccines for RSV and provide targets for novel antiviral agents. This project will advance the NIH Mission of developing “fundamental knowledge to extend healthy life and reduce the burdens of illness.”