权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

基本信息

批准号：
10542423
负责人：
Mark E. Peeples
金额：
$ 36.95万
依托单位：
RESEARCH INST NATIONWIDE CHILDREN'S HOSP
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-12-01 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10542423
关键词：
Affect Amino Acid Sequence Antiviral Agents Attenuated Attenuated Vaccines Binding Binding Proteins Bronchiolitis CX3C Chemokines Cell Line Cell membrane Cells Characteristics Child Cilia Classification Data Elderly Family Fractalkine G-Protein-Coupled Receptors GTP-Binding Proteins Genes Glycoproteins Goals Hospitalization Human Hydrophobicity Immune Immunocompromised Host Infant Infection Integral Membrane Protein Knowledge Laboratories Length Leukocytes Life Ligands Link Methionine Mission Modification Monomeric GTP-Binding Proteins Mucins N-terminal Neutralizing antibody assay Nose Open Reading Frames Paramyxovirus Phenotype Pneumonia Pneumovirus Polysaccharides Positioning Attribute Post-Translational Protein Processing Production Proteins Recombinant Delta Chemokine Reducing Agents Respiratory Syncytial Virus Infections Respiratory Syncytial Virus Vaccines Respiratory syncytial virus Role Serine Serum Signal Transduction Site Structure Threonine Tissue Donors Trachea Translations United States National Institutes of Health Vaccines Variant Viral Proteins Virion Virus Virus Receptors airway epithelium antiviral drug development burden of illness cell immortalization cell motility disulfide bond drug candidate improved insight migration monocyte monomer neutralizing antibody novel pathogen protein function protein structure receptor sugar vaccine candidate

项目摘要

Abstract: Respiratory syncytial virus (RSV) is the most frequent cause of hospitalization for infants and young children, but no vaccines or antiviral drugs are yet available. RSV infects the cells that line the nose, trachea and smaller airways. The overall goal of the laboratory is to understand how RSV infects its target cell, the ciliated airway cell, and to use that information to develop better vaccine and antiviral drug candidates. This laboratory uses primary well differentiated human airway epithelial cultures (HAECs) to study RSV infection. These HAECs have recently been used to identify an important RSV receptor on the ciliated airway cells. Preliminary data presented here demonstrate that the RSV produced by these HAECs is much more infectious for HAECs than for immortalized cells and its attachment, G, glycoprotein is responsible for this difference. The G protein is modified differently in HAECs as it passes through the cell, on its way to being incorporated into the RSV virion at the plasma membrane and this modification may be responsible for its enhanced activity. This project will identify the modification and the mechanism by which it is made. RSV also produces a secreted form of the G protein that triggers immune cells to migrate toward RSV-infected cells. This project will also determine if this secreted G protein is modified like the full-length version, and if its signaling activity is changed or enhanced by its modification, similar to the full-length G protein. Once the modification of the G protein and the secreted G protein are identified, and the mechanism by which they are modified are identified, this information could enable the production of more effective and economical live attenuated vaccines for RSV and provide targets for novel antiviral agents. This project will advance the NIH Mission of developing “fundamental knowledge to extend healthy life and reduce the burdens of illness.”

抽象的：呼吸道合胞病毒（RSV）是婴幼儿住院的最常见原因，但目前还没有疫苗或抗病毒药物。 RSV 感染鼻子、气管和较小部位的细胞航空公司。该实验室的总体目标是了解 RSV 如何感染其靶细胞（纤毛气道）细胞，并利用该信息来开发更好的疫苗和抗病毒候选药物。本实验室使用原代分化良好的人气道上皮培养物 (HAEC) 用于研究 RSV 感染。这些HAEC有最近被用来鉴定纤毛气道细胞上的重要 RSV 受体。提供的初步数据这里证明这些 HAEC 产生的 RSV 对 HAEC 的传染性比对永生化细胞及其附着物 G 糖蛋白造成了这种差异。 G蛋白被修饰在 HAEC 中，当它穿过细胞时，在被整合到 RSV 病毒体中的过程中，其变化方式有所不同。质膜和这种修饰可能是其活性增强的原因。该项目将确定修改及其进行的机制。 RSV 还产生分泌形式的 G 蛋白触发免疫细胞向 RSV 感染细胞迁移。该项目还将确定该分泌物是否 G 蛋白像全长版本一样被修饰，如果它的信号活性被改变或增强，修饰，类似于全长G蛋白。一旦修饰G蛋白和分泌G蛋白确定了它们，并确定了修改它们的机制，这些信息可以使生产更有效、更经济的 RSV 减毒活疫苗，并为新型疫苗提供靶点抗病毒剂。该项目将推进 NIH 的使命，即开发“扩展基础知识” 健康生活并减少疾病负担。”