Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes.
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 dev...
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Public Library of Science (PLoS)
2021-03-01
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| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001143&type=printable |
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| author | Neal G Ravindra Mia Madel Alfajaro Victor Gasque Nicholas C Huston Han Wan Klara Szigeti-Buck Yuki Yasumoto Allison M Greaney Victoria Habet Ryan D Chow Jennifer S Chen Jin Wei Renata B Filler Bao Wang Guilin Wang Laura E Niklason Ruth R Montgomery Stephanie C Eisenbarth Sidi Chen Adam Williams Akiko Iwasaki Tamas L Horvath Ellen F Foxman Richard W Pierce Anna Marie Pyle David van Dijk Craig B Wilen |
| author_facet | Neal G Ravindra Mia Madel Alfajaro Victor Gasque Nicholas C Huston Han Wan Klara Szigeti-Buck Yuki Yasumoto Allison M Greaney Victoria Habet Ryan D Chow Jennifer S Chen Jin Wei Renata B Filler Bao Wang Guilin Wang Laura E Niklason Ruth R Montgomery Stephanie C Eisenbarth Sidi Chen Adam Williams Akiko Iwasaki Tamas L Horvath Ellen F Foxman Richard W Pierce Anna Marie Pyle David van Dijk Craig B Wilen |
| author_sort | Neal G Ravindra |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-953d8b25aa2b462bb1a23148fd6012d7 |
| institution | OA Journals |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2021-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-953d8b25aa2b462bb1a23148fd6012d72025-08-20T02:18:15ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852021-03-01193e300114310.1371/journal.pbio.3001143Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes.Neal G RavindraMia Madel AlfajaroVictor GasqueNicholas C HustonHan WanKlara Szigeti-BuckYuki YasumotoAllison M GreaneyVictoria HabetRyan D ChowJennifer S ChenJin WeiRenata B FillerBao WangGuilin WangLaura E NiklasonRuth R MontgomeryStephanie C EisenbarthSidi ChenAdam WilliamsAkiko IwasakiTamas L HorvathEllen F FoxmanRichard W PierceAnna Marie PyleDavid van DijkCraig B WilenThere 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.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001143&type=printable |
| spellingShingle | Neal G Ravindra Mia Madel Alfajaro Victor Gasque Nicholas C Huston Han Wan Klara Szigeti-Buck Yuki Yasumoto Allison M Greaney Victoria Habet Ryan D Chow Jennifer S Chen Jin Wei Renata B Filler Bao Wang Guilin Wang Laura E Niklason Ruth R Montgomery Stephanie C Eisenbarth Sidi Chen Adam Williams Akiko Iwasaki Tamas L Horvath Ellen F Foxman Richard W Pierce Anna Marie Pyle David van Dijk Craig B Wilen Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. PLoS Biology |
| title | Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. |
| title_full | Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. |
| title_fullStr | Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. |
| title_full_unstemmed | Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. |
| title_short | Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. |
| title_sort | single cell longitudinal analysis of sars cov 2 infection in human airway epithelium identifies target cells alterations in gene expression and cell state changes |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001143&type=printable |
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