Deciphering mechanisms of COVID-19 induced anosmia

项目摘要/摘要 在这项竞争性修订提案中，我们试图研究Covid- 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中断，嗅觉受体(OR)下调 基因表达。由于新冠肺炎感染预计会引起抗病毒反应，因此我们假设 核结构和OR表达的中断是已报道的受感染患者嗅觉障碍的原因 病人。因此，我们建议分析人类嗅觉上皮的尸检，以破译Covid- 19种感染破坏了OR转录所需的基因组相互作用。我们将在以下方面补充我们的研究 用感染SARS-CoV-2的小鼠进行实验的人类身体解剖。RNA-seq、原位hIC和 人和小鼠的免疫组织化学实验将揭示冠状病毒感染的分子机制。 19导致嗅觉功能障碍。我们的实验将提供关键的洞察力，以了解 病毒劫持宿主细胞的分子和生理过程，为 预防、诊断和治疗新冠肺炎感染。

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.