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。呼吸道合胞病毒感染鼻子、气管和更小的细胞。 航空公司.实验室的总体目标是了解呼吸道合胞病毒如何感染其靶细胞--纤毛气道 细胞，并利用这些信息开发更好的疫苗和抗病毒候选药物。该实验室使用 原代分化良好的人气道上皮培养物（HAEC）以研究RSV感染。这些HAEC具有 最近被用于鉴定纤毛气道细胞上的重要RSV受体。初步数据 这里证明了由这些HAEC产生的RSV对HAEC的感染性比对 永生化细胞及其附着物G糖蛋白是造成这种差异的原因。G蛋白被修饰 当它通过细胞时，在HAEC中的不同，在其被掺入RSV病毒体的过程中， 质膜和这种修饰可能是其活性增强的原因。该项目将确定 改变和改变的机制。呼吸道合胞病毒还产生一种分泌形式的G蛋白 触发免疫细胞向感染RSV的细胞迁移。该项目还将确定， G蛋白像全长版本一样被修饰，如果它的信号活性被改变或增强， 修饰，类似于全长G蛋白。一旦G蛋白的修饰和分泌的G蛋白 识别，并确定它们被修改的机制，这些信息可以使 生产更有效和经济的RSV减毒活疫苗，并为新的RSV疫苗提供靶点。 抗病毒剂。该项目将推进国家卫生研究院的使命，即发展“基础知识， 健康生活，减轻疾病负担”。

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.”