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

Mechanisms of actin cytoskeleton modulation by Pneumoviruses

肺病毒调节肌动蛋白细胞骨架的机制

基本信息

批准号：
10320116
负责人：
Rebecca E. Dutch
金额：
$ 10.4万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-06-11 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10320116
关键词：
Actins Address Affect Affinity Chromatography Bacteria Binding Biochemical Biochemistry Biological Biological Assay Biological Models Biophysics Bronchiolitis Calorimetry Cell physiology Cells Cellular Morphology Cellular biology Childhood Co-Immunoprecipitations Complex Coupled Cytoskeletal Proteins Cytoskeleton Data Deuterium Disease Dyes Elderly Elements Family Fluorescent in Situ Hybridization Human Human Metapneumovirus Hybrids Hydrogen Immunocompromised Host In Vitro Individual Infection Life Cycle Stages Ligation Lower Respiratory Tract Infection Mass Spectrum Analysis Mediating Microscopy Modification Molecular Molecular Sieve Chromatography Mutation Analysis NMR Spectroscopy Nature Nucleocapsid Pathogenesis Phosphoproteins Physiological Play Pneumovirus Pneumovirus Infections Population Process Proteins RNA RNA Viruses Respiratory Syncytial Virus Infections Respiratory Tract Infections Respiratory syncytial virus Role Structure System Testing Time Titrations Viral Viral Proteins Virus Virus Diseases Virus Replication X-Ray Crystallography airway epithelium cell motility cellular targeting effective therapy human pathogen insight intercellular communication light scattering member mutant new therapeutic target novel pathogenic virus polymerization respiratory pathogen structural biology therapeutic development therapeutic target viral RNA virology

项目摘要

The actin cytoskeleton controls key cellular processes, including cell morphology, motility, and intercellular communication. Many viral pathogens exploit the actin cytoskeletal machinery by a variety of unique mechanisms to facilitate viral infection, replication, and egress. Currently, the molecular underpinnings of these viral mechanisms remain poorly defined for a majority of viruses, including members of the Pneumoviridae family. Human respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are non-segmented negative strand RNA viruses that are members of the recently created Pneumoviridae family. RSV and HMPV cause significant disease, including bronchiolitis and lower respiratory tract infection in the pediatric population, elderly, and immunocompromised individuals. Recent studies from our groups and others have implicated interactions between actin or actin-interacting proteins and specific pneumovirus proteins in replication and viral spread; however, the mechanisms and cellular targets required for facilitating actin rearrangements remain unknown. Our overall hypothesis is that a cascade of specific interactions between pneumovirus proteins and the actin cytoskeleton regulates key steps in viral infection, including formation of novel structures critical for virus cell-to-cell spread. Our collaborative team, with expertise in virology, cell biology, biochemistry, and structural biology, will test our hypothesis through three specific aims. First, we will dissect the interactions between RSV and HMPV matrix (M) proteins and phosphoproteins (P) that regulate the actin cytoskeleton within an infected cell. Second, we will determine the biochemical and structural basis for HMPV phosphoprotein/matrix/actin complex and RSV P/M/actin complex. Finally, we will determine the mechanisms of intercellular extension formation, stabilization, and utilization in viral spread. At the completion of these studies, we expect to define molecular mechanisms by which RSV and HMPV interact with and modulate the host actin cytoskeleton during virus replication, define key elements needed for this modulation, and understand the molecular details of cell-to-cell spread through intercellular extensions, thus providing critical new insights that may be applicable in multiple viral systems.

肌动蛋白细胞骨架控制关键的细胞过程，包括细胞形态、运动和细胞间