tetano
Editor, Senior Moderator
PLoS Biol
. 2021 Mar 17;19(3):e3001143.
doi: 10.1371/journal.pbio.3001143. Online ahead of print.
Single-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 Ravindra[SUP] 1 2 [/SUP], Mia Madel Alfajaro[SUP] 3 4 [/SUP], Victor Gasque[SUP] 1 2 5 6 [/SUP], Nicholas C Huston[SUP] 7 [/SUP], Han Wan[SUP] 8 [/SUP], Klara Szigeti-Buck[SUP] 9 10 11 [/SUP], Yuki Yasumoto[SUP] 9 10 11 [/SUP], Allison M Greaney[SUP] 12 [/SUP], Victoria Habet[SUP] 13 [/SUP], Ryan D Chow[SUP] 14 [/SUP], Jennifer S Chen[SUP] 3 4 [/SUP], Jin Wei[SUP] 3 4 [/SUP], Renata B Filler[SUP] 3 4 [/SUP], Bao Wang[SUP] 3 4 [/SUP], Guilin Wang[SUP] 15 [/SUP], Laura E Niklason[SUP] 12 16 [/SUP], Ruth R Montgomery[SUP] 17 [/SUP], Stephanie C Eisenbarth[SUP] 3 4 [/SUP], Sidi Chen[SUP] 3 4 14 [/SUP], Adam Williams[SUP] 18 [/SUP], Akiko Iwasaki[SUP] 4 19 [/SUP], Tamas L Horvath[SUP] 9 10 11 [/SUP], Ellen F Foxman[SUP] 3 4 [/SUP], Richard W Pierce[SUP] 13 [/SUP], Anna Marie Pyle[SUP] 14 19 [/SUP], David van Dijk[SUP] 1 2 [/SUP], Craig B Wilen[SUP] 3 4 [/SUP]
Affiliations
Abstract
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.
. 2021 Mar 17;19(3):e3001143.
doi: 10.1371/journal.pbio.3001143. Online ahead of print.
Single-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 Ravindra[SUP] 1 2 [/SUP], Mia Madel Alfajaro[SUP] 3 4 [/SUP], Victor Gasque[SUP] 1 2 5 6 [/SUP], Nicholas C Huston[SUP] 7 [/SUP], Han Wan[SUP] 8 [/SUP], Klara Szigeti-Buck[SUP] 9 10 11 [/SUP], Yuki Yasumoto[SUP] 9 10 11 [/SUP], Allison M Greaney[SUP] 12 [/SUP], Victoria Habet[SUP] 13 [/SUP], Ryan D Chow[SUP] 14 [/SUP], Jennifer S Chen[SUP] 3 4 [/SUP], Jin Wei[SUP] 3 4 [/SUP], Renata B Filler[SUP] 3 4 [/SUP], Bao Wang[SUP] 3 4 [/SUP], Guilin Wang[SUP] 15 [/SUP], Laura E Niklason[SUP] 12 16 [/SUP], Ruth R Montgomery[SUP] 17 [/SUP], Stephanie C Eisenbarth[SUP] 3 4 [/SUP], Sidi Chen[SUP] 3 4 14 [/SUP], Adam Williams[SUP] 18 [/SUP], Akiko Iwasaki[SUP] 4 19 [/SUP], Tamas L Horvath[SUP] 9 10 11 [/SUP], Ellen F Foxman[SUP] 3 4 [/SUP], Richard W Pierce[SUP] 13 [/SUP], Anna Marie Pyle[SUP] 14 19 [/SUP], David van Dijk[SUP] 1 2 [/SUP], Craig B Wilen[SUP] 3 4 [/SUP]
Affiliations
- PMID: 33730024
- DOI: 10.1371/journal.pbio.3001143
Abstract
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.