Ace2 in the healthy and inflamed taste system

Ace2 在健康和炎症味觉系统中的作用

基本信息

批准号：
10463442
负责人：
Lin Gan
金额：
$ 23.1万
依托单位：
AUGUSTA UNIVERSITY
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：
2022-03-01 至 2024-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10463442
关键词：
2019-nCoV ACE2 Address Affect Ageusia Aldosterone Angiotensin II Animal Model Anosmia Anterior Anti-Inflammatory Agents Antibodies Applications Grants Automobile Driving Behavior Binding Biological Blood Pressure Blood Vessels COVID-19 COVID-19 pandemic COVID-19 patient Cathepsins Cell Count Cells Chimeric Proteins Coughing Development Disease Down-Regulation Epidemic Epithelial Esthesia Exploratory/Developmental Grant Fatigue Fever Fluid Balance Functional disorder Future Genetic Hormones Human Immune response Infection Inflammation Inflammatory Knock-in Knock-in Mouse Knock-out Knockout Mice Knowledge Lipopolysaccharides LoxP-flanked allele Maps Measures Mediating Modeling Mouse Strains Mus Nerve Neural Pathways Neuroglia Neurons Organ Pathogenesis Pathway interactions Patients Peptide Hydrolases Peripheral Persons Population Proteins Quality of life Receptor Cell Renin-Angiotensin System Reporter Research Respiratory distress Role SARS coronavirus SARS-CoV-2 infection SARS-CoV-2 spike protein Severe Acute Respiratory Syndrome Smell Perception Stimulus Structure TMPRSS2 gene Tactile Taste Buds Taste Perception Testing Tropism Viral Virus Virus Diseases afferent nerve base behavioral response cell type chorda tympani common symptom insight lung injury member mouse model negative affect nerve injury neurophysiology novel nutrition patient subsets receptor receptor binding relating to nervous system response taste system

项目摘要

PROJECT SUMMARY / ABSTRACT Taste deficits are prevalent in people infected with SARS-CoV-2, the virus responsible for the global COVID-19 pandemic. The loss of taste sensation negatively affects nutrition and quality of life and in some patients this deficit is long-lasting. The biological basis for taste loss due to SARS-CoV-2 is largely unknown. Our preliminary results demonstrate that the ACE2 receptor and TMPRSS2 which together mediate SARS-CoV-2 host cell entry are expressed in taste buds indicating their potential for viral infection. The function of taste cell ACE2, also a member of the renin-angiotensin system that regulates fluid balance, is unknown. We have developed three novel genetic mouse strains to overcome the limitations of currently available mouse models. In aim 1 we map ACE2 reporter expression to determine which taste receptor cell populations and pathways are potential targets of SARS-CoV-2. In aim 2 we test how lingual epithelium-specific ACE2 contributes to taste receptor cell dynamics and neurophysiological taste responses under baseline and inflammatory conditions. We will also test how taste function is affected by human SARS-CoV-2 spike protein in a humanized ACE2 knock-in mouse. Our hypothesis predicts that taste buds are SARS-CoV-2 targets, that taste ACE2 contributes to taste function and is protective during inflammation, and that SARS-CoV-2 spike protein will exacerbate damage in taste buds and depress neural taste responses under inflammatory conditions. This R21 Exploratory / Developmental grant application addresses the urgent need for fundamental insights to mechanisms underlying taste dysregulation in people with COVID-19.

项目摘要 /摘要在感染SARS-COV-2的人中，味道不足是普遍的，该病毒负责全球共同19-19大流行。味觉失去对营养和质量产生负面影响生活和某些患者的这种赤字是长期的。由于 SARS-COV-2在很大程度上未知。我们的初步结果表明ACE2受体和TMPRSS2一起介导SARS-COV-2宿主细胞进入的味蕾中表达表明其病毒感染的潜力。味觉细胞ACE2的功能，也是调节流体平衡的肾素 - 血管紧张素系统尚不清楚。我们已经发展了三种新型的遗传小鼠菌株来克服当前可用小鼠的局限性型号。在AIM 1中，我们绘制ACE2报告基因表达式以确定哪种味觉受体细胞种群和途径是SARS-COV-2的潜在目标。在AIM 2中，我们测试舌上皮特异性ACE2有助于味觉受体细胞动力学和神经生理学在基线和炎症条件下的口味反应。我们还将测试口味功能受到人源化ACE2敲入中人类SARS-COV-2峰值蛋白的影响老鼠。我们的假设预测味蕾是SARS-COV-2目标，味觉ACE2 有助于味觉功能，并且在炎症期间具有保护性，而SARS-COV-2 Spike 蛋白质会加剧味蕾的损害，并在下面降低神经味反应炎症条件。此R21探索性 /发展赠款申请涉及迫切需要对人们味道失调的机制的基本见解与Covid-19。