In:
PLOS Biology, Public Library of Science (PLoS), Vol. 19, No. 3 ( 2021-3-17), p. e3001143-
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3001143
DOI:
10.1371/journal.pbio.3001143.g001
DOI:
10.1371/journal.pbio.3001143.g002
DOI:
10.1371/journal.pbio.3001143.g003
DOI:
10.1371/journal.pbio.3001143.g004
DOI:
10.1371/journal.pbio.3001143.g005
DOI:
10.1371/journal.pbio.3001143.g006
DOI:
10.1371/journal.pbio.3001143.s001
DOI:
10.1371/journal.pbio.3001143.s002
DOI:
10.1371/journal.pbio.3001143.s003
DOI:
10.1371/journal.pbio.3001143.s004
DOI:
10.1371/journal.pbio.3001143.s005
DOI:
10.1371/journal.pbio.3001143.s006
DOI:
10.1371/journal.pbio.3001143.s007
DOI:
10.1371/journal.pbio.3001143.s008
DOI:
10.1371/journal.pbio.3001143.s009
DOI:
10.1371/journal.pbio.3001143.s010
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2021
ZDB Id:
2126773-X
