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: 8967134
• 负责人: Mark E. Peeples
• 金额: $ 36.2万
• 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 2017-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8967134
• 关键词: Admission activity; Antiviral Agents; Apical; Basal Cell; Binding; Binding Proteins; 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; 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，在老年人群中，RSV是流感病毒后第二大最常见的呼吸道感染死亡原因。大多数RSV感染在细胞水平上的研究都是在培养的，永生的细胞中进行的。在这些细胞中，RSV与硫酸乙酰肝素（HS）结合，这是细胞表面上复杂的寡糖，作为其主要受体启动感染。在主要分化的人类气道上皮（HAE）培养物中，这是RSV靶向靶标的气道细胞的绝佳模型，RSV仅感染纤毛的细胞，并且仅通过顶部表面感染。但是该表面没有可检测到的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与之结合的RSV附着蛋白上的受体和位点。两者都将为开发针对RSV的新型抗病毒剂提供新的目标。