期刊
PLOS BIOLOGY
卷 19, 期 3, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pbio.3001143
关键词
-
资金
- NIH [K08 AI128043, R21AI133440, R01AI141609, K08AI119139]
- Burroughs Wellcome Fund Career Award for Medical Scientists, Robert Leet and Clara Guthrie Patterson Trust
- Ludwig Family Foundation
- Mathers Charitable Foundation
- Fast Grant (Emergent Ventures)
The study provides insights into the replication, cell tropism, and host-viral interactions of SARS-CoV-2 in human bronchial epithelial cells. It highlights ciliated cells as a major initial target of infection, with the virus later expanding its cell tropism to include other epithelial cell types. Infection induces expression of interferons and interferon-stimulated genes, providing a detailed characterization of gene expression and cell state changes associated with SARS-CoV-2 infection in the human airway.
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.
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