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: 8239169
• 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 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8239169
• 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. PUBLIC HEALTH RELEVANCE: Respiratory syncytial virus (RSV) is the most important respiratory pathogen for infants, and behind only influenza virus for the elderly. Much of what we know about the replication of RSV comes from studying the virus in immortalized cells. But it now appears that the first step in RSV infection, attachment to the target cell, is completely different in airway cells. This project will explore RSV infection of primary cells that closely model the airway epithelium, from both the virus and cell perspective.

描述（由申请方提供）：呼吸道合胞病毒（RSV）感染是儿童住院的最常见原因，在老年人群中，RSV是仅次于流感病毒的呼吸道感染死亡的第二常见原因。RSV感染在细胞水平上的大多数研究已经在培养的永生化细胞中进行。在这些细胞中，RSV与硫酸乙酰肝素（HS）（细胞表面的一种复合寡糖）结合，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（RSV靶向气道细胞的优良模型）中，RSV仅感染纤毛细胞且仅通过顶端表面感染。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进入这些细胞。本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，这两者都将为开发抗RSV的新型抗病毒药物提供新的靶点。 公共卫生相关性：呼吸道合胞病毒（RSV）是婴幼儿最重要的呼吸道病原体，仅次于老年人的流感病毒。我们对RSV复制的大部分了解来自于对永生化细胞中病毒的研究。但现在看来，RSV感染的第一步，附着在靶细胞上，在气道细胞中是完全不同的。本项目将从病毒和细胞的角度探讨RSV感染与气道上皮细胞密切相关的原代细胞。