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.

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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Main Authors: 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
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-03-01
Series:PLoS Biology
Online Access:https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001143&type=printable
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Summary: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.
ISSN:1544-9173
1545-7885

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