Deciphering mechanisms of COVID-19 induced anosmia

解读 COVID-19 引起的嗅觉丧失的机制

• 批准号: 10176800
• 负责人: Stavros Lomvardas
• 金额: $ 20.25万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10176800
• 关键词: 2019-nCoV; Anosmia; Antiviral Agents; Antiviral Response; Architecture; Autopsy; COVID-19; COVID-19 pandemic; Cells; Complement; Data; Diagnosis; Down-Regulation; Functional disorder; Gene Expression; Genetic Transcription; Genomics; Human; Immunohistochemistry; In Situ; Infection; Inflammatory; Molecular; Molecular Mechanisms of Action; Mus; Nuclear; Olfactory Epithelium; Pathway interactions; Patients; Physiological Processes; Prevention; Reporting; Smell Perception; Virus; experimental study; insight; novel diagnostics; novel therapeutics; olfactory receptor; receptor expression; transcriptome sequencing

Project Summary/Abstract In this Competitive Revision proposal, we seek to investigate the non-cell autonomous effects of Covid- 19 infections in olfaction. Our preliminary data suggest that induction of pro-inflammatory/antiviral pathways result in disruption of inter-chromosomal genomic interactions, and downregulation of Olfactory Receptor (OR) gene expression. Since antiviral responses are expected be elicited upon Covid-19 infection, we hypothesize that disruptions in nuclear architecture and OR expression account for the reported olfactory deficits in infected patients. Thus, we propose to analyze human autopsies of the olfactory epithelium, to decipher whether Covid- 19 infections disrupt genomic interactions required for OR transcription. We will complement our studies in human autopsies with experiments using mice infected with SARS-CoV-2. RNA-seq, in situ HiC and immunohistochemistry experiments in human and mice will reveal the molecular mechanisms by which Covid- 19 induces olfactory dysfunction. Our experiments will provide critical insight to the mechanisms by which the virus hijacks molecular and physiological processes of the host cell, opening new potential avenues for the prevention, diagnosis and treatment of Covid-19 infection.

项目总结/摘要 在这份竞争性修订提案中，我们试图研究新冠肺炎的非细胞自主效应， 嗅觉感染19例。我们的初步数据表明，诱导促炎/抗病毒途径 导致染色体间基因组相互作用的破坏和嗅觉受体（OR）的下调 基因表达。由于预期在COVID-19感染后会引发抗病毒反应，我们假设 核结构和OR表达的破坏解释了受感染的人的嗅觉缺陷， 患者因此，我们建议分析人类嗅觉上皮的尸检，以破译新冠肺炎是否是由人类的嗅觉上皮引起的。 19种感染破坏OR转录所需的基因组相互作用。我们将补充我们的研究， 用感染SARS-CoV-2的小鼠进行实验。RNA-seq、原位HiC和 人类和小鼠的免疫组织化学实验将揭示新冠病毒的分子机制， 19诱导嗅觉功能障碍。我们的实验将提供关键的洞察机制， 病毒劫持宿主细胞的分子和生理过程，为病毒的传播开辟了新的潜在途径。 预防、诊断和治疗新冠肺炎感染。