Respiratory Syncytial Virus Targeting of the Human Airway Epithelium

描述（由申请人提供）：呼吸道合胞病毒（RSV）感染是儿童住院的最常见原因，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常见原因。大多数RSV感染在细胞水平上的研究都是在培养的、永生化的细胞中进行的。在这些细胞中，RSV结合硫酸肝素（HS），一种细胞表面的复合寡糖，作为其主要受体启动感染。在原代、分化良好的人气道上皮（HAE）培养物中，RSV仅感染纤毛细胞，并且仅通过根尖表面感染，这是RSV靶向气道细胞的良好模型。但这个表面没有检测到HS。因此，RSV必须使用不同的受体进入这些细胞。该项目的目标是确定该受体和RSV附着蛋白上与其结合的位点。两者都将为开发针对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.