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Single cell resolution of SARS-CoV-2 tropism, antiviral responses, and susceptibility to therapies in primary human airway epithelium
bioRxiv - Microbiology Pub Date : 2020-10-19 , DOI: 10.1101/2020.10.19.343954
Jessica K. Fiege , Joshua M. Thiede , Hezkiel Nanda , William E. Matchett , Patrick J. Moore , Noe Rico Montanari , Beth K. Thielen , Jerry Daniel , Emma Stanley , Ryan C. Hunter , Vineet D. Menachery , Steven S. Shen , Tyler D. Bold , Ryan A. Langlois

The human airway epithelium is the initial site of SARS-CoV-2 infection. We used flow cytometry and single cell RNA-Sequencing to understand how the heterogeneity of this diverse cell population contributes to elements of viral tropism and pathogenesis, antiviral immunity, and treatment response to remdesivir. We found that, while a variety of cell types are susceptible to infection, ciliated cells are a predominant cell target for SARS-CoV-2. Remdesivir treatment effectively inhibited viral replication across cell types, and blunted hyperinflammatory responses. We also found that heavily infected epithelial cells demonstrate impaired IFN signaling and express abundant IL-6, a potential mediator of COVID-19 pathogenesis.

中文翻译:

人原发性气道上皮细胞的SARS-CoV-2向性,抗病毒反应和对治疗敏感性的单细胞分辨率

人呼吸道上皮是SARS-CoV-2感染的最初部位。我们使用流式细胞仪和单细胞RNA测序来了解这种多样化细胞群体的异质性如何促进病毒向性和发病机理,抗病毒免疫以及对瑞姆昔韦的治疗反应。我们发现,尽管多种细胞类型都易于感染,但纤毛细胞是SARS-CoV-2的主要细胞靶标。Remdesivir治疗有效抑制了跨细胞类型的病毒复制,并减弱了炎症反应。我们还发现,重度感染的上皮细胞表现出受损的IFN信号传导并表达丰富的IL-6,这可能是COVID-19发病机理的潜在介质。
更新日期:2020-10-20
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