Respiratory Syncytial Virus Targeting of the Human Airway Epithelium

靶向人类气道上皮的呼吸道合胞病毒

• 批准号: 8775191
• 负责人: Mark E. Peeples
• 金额: $ 40.9万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-12-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8775191
• 关键词: Admission activity; Antiviral Agents; Apical; Basal Cell; Binding; Cause of Death; Cell Line; Cell surface; Cells; Cessation of life; Child; Cilia; Columnar Cell; Complex; Data; Development; Diagnosis; Elderly; Epithelial; Epithelial Cells; GTP-Binding Proteins; Glycosaminoglycans; Goals; Health; Hela Cells; Heparitin Sulfate; Hospitals; Human; Infant; Infection; Insecta; Modeling; Modification; Oligosaccharides; Organ; Outcome; Population; Post-Translational Protein Processing; Process; Protein Binding; RNA Viruses; Research; Respiratory Syncytial Virus Infections; Respiratory Tract Infections; Respiratory syncytial virus; Site; Surface; Testing; Vaccines; Virion; Virus; Virus Diseases; Virus Receptors; airway epithelium; base; drug development; end of life; immortalized cell; in vivo; in vivo Model; influenzavirus; insight; novel; pathogen; prevent; receptor; respiratory

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.

描述（由申请人提供）：呼吸道合胞病毒（RSV）感染是儿童入院的最常见原因，而在老年人群中，RSV 是继流感病毒之后第二大常见的呼吸道感染死亡原因。大多数细胞水平上 RSV 感染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 与硫酸乙酰肝素 (HS) 结合，硫酸乙酰肝素是细胞表面的一种复杂寡糖，作为其启动感染的主要受体。在原代、分化良好的人气道上皮 (HAE) 培养物中，RSV 是 RSV 靶向的气道细胞的绝佳模型，RSV 仅感染纤毛细胞，并且仅通过顶端表面感染。但该表面没有可检测到的 H2S。因此，RSV 必须使用不同的受体才能进入这些细胞。该项目的目标是识别该受体以及 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。