Innate immune responses to SARS-CoV-2 infection in the olfactory epithelium

研究综述 突发性嗅觉丧失已被公认为新冠肺炎的常见症状。它的作用机制 新冠肺炎相关的嗅觉功能障碍尚不清楚。嗅觉缺陷的程度是否预示着 新冠肺炎中的长期神经系统疾病尚未进行评估。最近的单细胞rna-seq分析 发现SARS-CoV-2的受体ACE2不是由嗅觉神经元表达的，而是由嗅觉神经元表达 由OE中的支持支持细胞(SUS)表达。因此，SUS单元格可能是入口单元格 在OE中输入SARS-CoV-2。OE中SARS-CoV-2感染的特征需要进一步确定。当前 观察表明，病毒感染是稀疏和局部性的。广泛分布的嗅觉感受器 据报道，在病毒感染下下调了基因表达，这表明可能存在分布广泛的病毒影响 来自OE的局部病毒感染。我们假设广泛存在的SUS细胞介导的炎症 由SARS-CoV-2引发的反应是新冠肺炎相关嗅觉丧失的原因。在这项研究中，我们 将表征嗅上皮对SARS-CoV-2的炎症反应并鉴定SUS细胞 特异性细胞因子的表达；我们将建立一个原代SUS细胞培养系统来检测病毒 SARS-CoV-2诱导的天然免疫反应中的识别途径和转录因子 将进一步确定SARS-CoV-2感染所致的嗅觉神经元功能缺陷。通过这件事 通过研究，我们将从机制上深入了解新冠肺炎相关的嗅觉损失。

RESEARCH SUMMARY Sudden-onset of olfactory loss has been recognized as a common COVID-19 symptom. The mechanism of COVID-19 related olfactory dysfunction is unknown. Whether the degree of olfactory deficit is indicative of any long-term neurological diseases in COVID-19 has not been evaluated. Recent single-cell RNA-seq analyses revealed that the receptor for SARS-CoV-2, ACE2, is not expressed by olfactory sensory neurons (OSNs) but are expressed by supporting sustentacular (Sus) cells in the OE. Therefore, Sus cells may be the entry cell type for SARS-CoV-2 in the OE. SARS-CoV-2 infection in the OE needs to be further characterized. Current observations indicate that the viral infection is sparse and localized. Widespread olfactory receptor downregulation has been reported under viral infection suggesting that there might be a distributed viral impact from localized viral infection in the OE. We hypothesize that widespread Sus cell mediated inflammatory response, triggered by SARS-CoV-2, is responsible for COVID-19 associated olfactory loss. In this study, we will characterize inflammatory responses to SARS-CoV-2 in the olfactory epithelium and identify Sus cell specific cytokine expressions; we will established a primary Sus cell culture system to examine viral recognition pathways and transcription factors involved in SARS-CoV-2 induced innate immune responses; we will further determine SARS-CoV-2 infection induced olfactory sensory neuron functional deficits. Through this study, we will gain mechanistic insight into COVID-19 associated olfactory loss.