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Modeling the contribution of coronavirus cellular tropism to viral pathogenesis

模拟冠状病毒细胞向性对病毒发病机制的贡献

基本信息

批准号：
10583101
负责人：
Beverly H Koller
金额：
$ 23.33万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-12-01 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10583101
关键词：
2019-nCoV ACE2 Acute Lung Injury Address Affect Alveolar Basal Cell Biological Models Breeding COVID-19 COVID-19 monitoring Cells Cellular Tropism Cessation of life Cognitive Coronavirus Cre driver DNA cassette Development Disease Disease Progression Distal Docking Enterobacteria phage P1 Cre recombinase Epithelial Cells Epithelium Event Gases Generations Genes Genomics Goals Goblet Cells Health Host Defense Human Immune response Individual Infection Initiator Codon Knock-in Knowledge Lung Lung diseases Mammalian Cell Modeling Mus Nasal Epithelium Nature Pathogenesis Pattern Peptide Initiation Factors Population Predisposition Prevalence Production Proliferating Receptor Cell Research Personnel Respiratory System Respiratory Tract Infections Role SARS coronavirus SARS-CoV-2 exposure SARS-CoV-2 infection Severity of illness Structure Study models System Therapeutic Therapeutic Intervention Tissues Transgenic Mice Transgenic Organisms Tropism Type II Epithelial Receptor Cell Validation Viral Viral Pathogenesis Virus Virus Diseases Virus Replication airway epithelium alveolar type II cell apical membrane cell type clinically relevant in vivo Model male model design mouse development mouse model novel coronavirus pathogen promoter protective pathway pulmonary function receptor restoration species difference tissue tropism tool vaccine development virus tropism

项目摘要

Summary The cell and tissue tropism of viruses is defined as the capacity of a virus to infect specific cells and tissues and is determined by both viral and cellular factors. An important factor for initiation of infection is cell entry, which is dependent on the ability of the virus to dock with its cognitive receptor. A growing understanding of species differences in ACE2 structure and, perhaps more importantly, in tissue specific patterns of expression has underscored the potential limitations in the use of mouse models for the study of disease pathogenesis of coronaviruses such as SARS-CoV-2 that rely on ACE2 for cellular entry. We propose to implement a strategy for the rapid generation of mouse models in which human ACE2 expression is limited to individual or multiple airway epithelial populations. Using these lines, we will examine the impact of the cellular pattern of ACE2 expression in the respiratory tract on the sequence of events following exposure to SARS-CoV2 coronavirus.

总结病毒的细胞和组织嗜性被定义为病毒感染的能力特定的细胞和组织，并由病毒和细胞因素决定。一个启动感染的重要因素是细胞进入，这取决于感染的能力。让病毒与其认知受体对接对物种的了解越来越多 ACE 2结构的差异，也许更重要的是组织特异性模式的差异，的表达强调了使用小鼠模型进行冠状病毒如SARS-CoV-2致病机理研究 ACE 2用于细胞进入。我们建议实施一项战略，小鼠模型，其中人ACE 2表达限于单个或多个气道上皮细胞群。使用这些行，我们将检查呼吸道中ACE 2表达的细胞模式对事件顺序的影响在接触SARS-CoV 2冠状病毒之后。