Ace2 in the healthy and inflamed taste system

项目总结/摘要 味觉缺陷在感染SARS-CoV-2的人中很普遍，该病毒负责 全球COVID-19大流行。味觉的丧失会对营养和品质产生负面影响 在某些患者中，这种缺陷是长期存在的。味觉丧失的生物学基础， SARS-CoV-2在很大程度上未知。我们的初步结果表明，ACE 2受体 和TMPRSS 2共同介导SARS-CoV-2宿主细胞进入，在味蕾中表达 表明它们有可能感染病毒。味觉细胞ACE 2的功能，也是 调节体液平衡的肾素-血管紧张素系统是未知的。我们已经开发 三种新的遗传小鼠品系，以克服目前可用的小鼠的局限性， 模型在目标1中，我们绘制ACE 2报告基因表达图，以确定哪个味觉受体细胞 人群和途径是SARS-CoV-2的潜在靶点。在aim 2中，我们测试了 上皮特异性ACE 2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味觉反应。我们还将测试如何品尝 在人源化ACE 2基因敲入中，人SARS-CoV-2刺突蛋白影响功能 老鼠.我们的假设预测味蕾是SARS-CoV-2的靶点， 有助于味觉功能，并在炎症期间起到保护作用， 蛋白质会加剧味蕾的损伤，并抑制神经味觉反应。 炎性条件。此R21探索/发展补助金申请解决了 迫切需要对人类味觉失调机制的基本见解 新冠肺炎

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.