Respiratory Syncytial Virus Targeting of the Human Airway Epithelium

描述(申请人提供)：呼吸道合胞病毒(RSV)感染是儿童入院的最常见原因，在老年人中，RSV是仅次于流感病毒的呼吸道感染死亡的第二大原因。大多数关于RSV感染的细胞水平的研究都是在培养的永生化细胞中进行的。在这些细胞中，RSV与细胞表面的一种复杂的低聚糖硫酸乙酰肝素(HS)结合，作为其启动感染的主要受体。在原代、分化良好的人类呼吸道上皮细胞(HAE)培养中，RSV仅感染纤毛细胞且仅通过根尖表面感染，这是RSV目标呼吸道细胞的优秀模型。但这个表面没有可检测到的HS。因此，RSV必须使用不同的受体才能进入这些细胞。该项目的目标是确定该受体以及与之结合的RSV附着蛋白上的位置。两者都将为开发抗RSV的新型抗病毒药物提供新的靶点。

DESCRIPTION (provided by applicant): Respiratory syncytial virus (RSV) infection is the most common cause of hospital admission for children, and in the elderly population RSV is the second most common cause of death from respiratory infection after influenza virus. Most studies of RSV infection on the cellular level have been performed in cultured, immortalized cells. In these cells, RSV binds to heparan sulfate (HS), a complex oligosaccharide on the cell surface, as its primary receptor to initiate infection. In primary, well differentiated human airway epithelial (HAE) cultures, an excellent model for the airway cells that RSV targets, RSV infects only ciliated cells and only via the apical surface. But this surface has no detectable HS. RSV must, therefore, use a different receptor to enter these cells. The goals of this project are to identify that receptor and the site on the RSV attachment protein that binds to it. Both will provide novel targets for the development of novel antiviral agents against RSV.