Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes.
Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes.
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DOI：
10.1371/journal.pbio.3001143
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发表时间：
2021-03
期刊：
影响因子：
9.8
通讯作者：
Wilen CB
中科院分区：
文献类型：
--
作者：
Ravindra NG;Alfajaro MM;Gasque V;Huston NC;Wan H;Szigeti-Buck K;Yasumoto Y;Greaney AM;Habet V;Chow RD;Chen JS;Wei J;Filler RB;Wang B;Wang G;Niklason LE;Montgomery RR;Eisenbarth SC;Chen S;Williams A;Iwasaki A;Horvath TL;Foxman EF;Pierce RW;Pyle AM;van Dijk D;Wilen CB
目前有有限的食品和药物管理局（FDA）批准的药物和疫苗用于治疗或预防2019冠状病毒病（COVID-19）。加强对严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）感染和发病机制的了解对于开发治疗药物至关重要。为了深入了解SARS-CoV-2的病毒复制、细胞嗜性和宿主-病毒相互作用，我们对实验感染的人支气管上皮细胞（HBEC）在气液界面（ALI）培养物中进行了一段时间的单细胞（sc）RNA测序（RNA-seq）。这揭示了新的多聚腺苷酸化病毒转录本，并强调纤毛细胞作为感染开始时的主要目标，我们通过电子和免疫荧光显微镜证实。在感染过程中，SARS-CoV-2的细胞嗜性扩展到其他上皮细胞类型，包括基底细胞和俱乐部细胞。感染诱导I型和III型干扰素（IFN）和白细胞介素（IL）-6但不诱导IL-1的细胞内在表达。这导致干扰素刺激基因（ISG）在感染细胞和旁观者细胞中表达。这提供了一个详细的表征基因，细胞类型和细胞状态的变化与SARS冠状病毒-2感染在人类气道。SARS-CoV-2感染的人气道上皮细胞的单细胞分析为病毒复制、细胞嗜性和宿主-病毒相互作用提供了新的见解。这项研究揭示了新的多聚腺苷酸化的病毒转录，纤毛细胞，后来延伸到其他上皮细胞类型，和细胞的内在表达的I型和III型干扰素和IL-6感染诱导，导致干扰素刺激的基因在感染和旁观者细胞的表达的偏好。
There are currently limited Food and Drug Administration (FDA)-approved drugs and vaccines for the treatment or prevention of Coronavirus Disease 2019 (COVID-19). Enhanced understanding of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and pathogenesis is critical for the development of therapeutics. To provide insight into viral replication, cell tropism, and host–viral interactions of SARS-CoV-2, we performed single-cell (sc) RNA sequencing (RNA-seq) of experimentally infected human bronchial epithelial cells (HBECs) in air–liquid interface (ALI) cultures over a time course. This revealed novel polyadenylated viral transcripts and highlighted ciliated cells as a major target at the onset of infection, which we confirmed by electron and immunofluorescence microscopy. Over the course of infection, the cell tropism of SARS-CoV-2 expands to other epithelial cell types including basal and club cells. Infection induces cell-intrinsic expression of type I and type III interferons (IFNs) and interleukin (IL)-6 but not IL-1. This results in expression of interferon-stimulated genes (ISGs) in both infected and bystander cells. This provides a detailed characterization of genes, cell types, and cell state changes associated with SARS-CoV-2 infection in the human airway. Single-cell analysis of human airway epithelial cells infected with SARS-CoV-2 provides novel insights into viral replication, cell tropism, and host-viral interactions. This study reveals novel polyadenylated viral transcripts, preferential tropism for ciliated cells that later extends to other epithelial cell types, and cell-intrinsic expression of type I and type III IFNs and IL6 induced by infection, resulting in expression of interferon-stimulated genes in both infected and bystander cells.
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DOI：
10.1038/nrmicro.2016.81
发表时间：
2016-08
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
de Wit E;van Doremalen N;Falzarano D;Munster VJ
通讯作者：
Munster VJ
影响因子：
64.5
作者：
Hou, Yixuan J.;Okuda, Kenichi;Baric, Ralph S.
通讯作者：
Baric, Ralph S.
DOI：
10.1056/nejmra0910061
发表时间：
2010-12-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Fahy JV;Dickey BF
通讯作者：
Dickey BF
影响因子：
5.4
作者：
Glowacka, Ilona;Bertram, Stephanie;Poehlmann, Stefan
通讯作者：
Poehlmann, Stefan
影响因子：
5.4
作者：
Goertz, G. P.;Fros, J. J.;Pijlman, G. P.
通讯作者：
Pijlman, G. P.