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 Biol
; 19(3): e3001143, 2021 03.
Article
in English
| MEDLINE | ID: covidwho-1138557
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Bronchi
/
Gene Expression
/
Single-Cell Analysis
/
SARS-CoV-2
/
COVID-19
Type of study:
Cohort study
/
Diagnostic study
/
Observational study
/
Prognostic study
Topics:
Vaccines
Limits:
Adult
/
Humans
Language:
English
Journal:
PLoS Biol
Journal subject:
Biology
Year:
2021
Document Type:
Article
Affiliation country:
Journal.pbio.3001143
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