Single cell resolution of SARS-CoV-2 tropism, antiviral responses, and susceptibility to therapies in primary human airway epithelium.
Single cell resolution of SARS-CoV-2 tropism, antiviral responses, and susceptibility to therapies in primary human airway epithelium.
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人类原代气道上皮中 SARS-CoV-2 趋向性、抗病毒反应和治疗敏感性的单细胞分辨率。
DOI：
10.1101/2020.10.19.343954
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Langlois,RyanA
中科院分区：
文献类型：
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作者：
Fiege,JessicaK;Thiede,JoshuaM;Nanda,Hezkiel;Matchett,WilliamE;Moore,PatrickJ;Montanari,NoeRico;Thielen,BethK;Daniel,Jerry;Stanley,Emma;Hunter,RyanC;Menachery,VineetD;Shen,StevenS;Bold,TylerD;Langlois,RyanA
人的呼吸道上皮细胞是SARS-CoV-2感染的起始部位。我们使用流式细胞术和单细胞RNA测序来了解这种不同细胞群体的异质性如何影响病毒的趋向性和致病机制、抗病毒免疫和对瑞希韦的治疗反应。我们发现，虽然多种上皮细胞类型对感染易感，但纤毛细胞是SARS-CoV-2的主要细胞靶点。感染这些细胞需要宿主蛋白酶TMPRSS2。重要的是，雷米昔韦治疗有效地抑制了病毒在不同细胞类型之间的复制，并钝化了炎症反应。在感染细胞内诱导干扰素反应的情况很少见，而且抗病毒基因特征存在显著的异质性，这与每个细胞中感染的负担不同。我们还发现，重度感染的分泌细胞表达丰富的IL-6，这可能是新冠肺炎发病的潜在介质。
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 epithelial cell types are susceptible to infection, ciliated cells are the predominant cell target of SARS-CoV-2. The host protease TMPRSS2 was required for infection of these cells. Importantly, remdesivir treatment effectively inhibited viral replication across cell types, and blunted hyperinflammatory responses. Induction of interferon responses within infected cells was rare and there was significant heterogeneity in the antiviral gene signatures, varying with the burden of infection in each cell. We also found that heavily infected secretory cells expressed abundant IL-6, a potential mediator of COVID-19 pathogenesis.