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.

项目摘要/摘要 在这项竞争性修订建议中，我们试图调查COVID的非单元自主效应 19嗅觉感染。我们的初步数据表明促炎/抗病毒途径的诱导 导致染色体间基因组相互作用的破坏，以及嗅觉受体的下调（OR） 基因表达。由于预计在19 covid-19感染后会引起抗病毒反应，因此我们假设 核结构和 / /或表达中的破坏说明了被感染的嗅觉缺陷 患者。因此，我们建议分析嗅觉上皮的人类尸检，以破译是否covid- 19感染破坏了或转录所需的基因组相互作用。我们将补充我们的研究 使用SARS-COV-2感染的小鼠进行实验尸检。 RNA-seq，原位HIC和 在人和小鼠中进行的免疫组织化学实验将揭示分子机制 19诱导嗅觉功能障碍。我们的实验将为您提供有关机制的关键见解 病毒劫持宿主细胞的分子和生理过程，为 预防，诊断和治疗19009感染。