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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Published in:PLoS biology 2021-03, Vol.19 (3), p.e3001143
Main Authors: Ravindra, Neal G, Alfajaro, Mia Madel, Gasque, Victor, Huston, Nicholas C, Wan, Han, Szigeti-Buck, Klara, Yasumoto, Yuki, Greaney, Allison M, Habet, Victoria, Chow, Ryan D, Chen, Jennifer S, Wei, Jin, Filler, Renata B, Wang, Bao, Wang, Guilin, Niklason, Laura E, Montgomery, Ruth R, Eisenbarth, Stephanie C, Chen, Sidi, Williams, Adam, Iwasaki, Akiko, Horvath, Tamas L, Foxman, Ellen F, Pierce, Richard W, Pyle, Anna Marie, van Dijk, David, Wilen, Craig B
Format: Article
Language:English
Subjects:
Adult
Biology and life sciences
Bronchi - pathology
Bronchi - virology
Cells, Cultured
Coronaviruses
COVID-19
COVID-19 - diagnosis
COVID-19 - immunology
COVID-19 - pathology
COVID-19 - virology
Epithelial cells
Epithelium
Epithelium - pathology
Epithelium - virology
Gene Expression
Gene sequencing
Humans
Immunity, Innate
Infections
Longitudinal Studies
Medicine and health sciences
Middle East respiratory syndrome
Mortality
Nucleocapsids
Polymerase chain reaction
Public health
Respiratory diseases
SARS-CoV-2 - genetics
SARS-CoV-2 - isolation & purification
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Single-Cell Analysis - methods
Target recognition
Transcriptome
Transcriptomes
Tropism
Viral diseases
Viral Tropism
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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:1545-7885
1544-9173
1545-7885
DOI:10.1371/journal.pbio.3001143