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.

概括病毒的细胞和组织向性定义为病毒感染细胞和组织的能力特定细胞和组织，由病毒和细胞因素决定。一个感染启动的重要因素是细胞进入，这取决于细胞的能力病毒与其认知受体对接。对物种的了解不断加深 ACE2 结构的差异，或许更重要的是组织特异性模式的差异表达强调了使用小鼠模型的潜在局限性对 SARS-CoV-2 等冠状病毒疾病发病机制的研究 ACE2 用于细胞进入。我们建议实施一项快速生成的战略人类 ACE2 表达仅限于单个或多个的小鼠模型气道上皮细胞群。使用这些线，我们将检查的影响呼吸道中 ACE2 表达的细胞模式对事件顺序的影响接触 SARS-CoV2 冠状病毒后。