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）是婴儿和幼儿住院的最常见原因，但是仍然没有疫苗或抗病毒药物。 RSV感染了鼻子，气管和较小的细胞航空公司。实验室的总体目标是了解RSV如何感染其目标电池，纤毛气道细胞，并使用该信息来开发更好的疫苗和抗病毒药物。该实验室使用主要分化的人类气道上皮培养物（HAEC）研究RSV感染。这些Haecs有最近，用于鉴定纤毛气道细胞上重要的RSV受体。提出的初步数据在这里证明，这些HAEC产生的RSV对Haecs比永生的细胞及其附着G糖蛋白是造成这种差异的原因。 G蛋白被修饰在HAEC中通过细胞时，其在途中将其纳入RSV病毒粒子的途中质膜和这种修饰可能是其增强活性的原因。这个项目将确定修改和制造的机制。 RSV还产生G蛋白的分泌形式这会触发免疫电池向RSV感染的细胞迁移。这个项目还将确定这是否分泌 G蛋白像全长版一样修饰，如果其信号活性被其更改或增强修饰，类似于全长G蛋白。一旦修饰G蛋白和分泌的G蛋白确定，确定修改的机制，此信息可以使生产RSV的更有效，更经济的活衰减疫苗，并为新颖抗病毒药。该项目将推进NIH的使命，即发展“基本知识以扩展健康的生活并减少疾病的伯恩斯。”