SARS-CoV-2 Infection of Pluripotent Stem Cell-Derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response.
Cell Stem Cell
; 27(6): 962-973.e7, 2020 12 03.
Article
in English
| MEDLINE | ID: covidwho-779662
ABSTRACT
A hallmark of severe COVID-19 pneumonia is SARS-CoV-2 infection of the facultative progenitors of lung alveoli, the alveolar epithelial type 2 cells (AT2s). However, inability to access these cells from patients, particularly at early stages of disease, limits an understanding of disease inception. Here, we present an in vitro human model that simulates the initial apical infection of alveolar epithelium with SARS-CoV-2 by using induced pluripotent stem cell-derived AT2s that have been adapted to air-liquid interface culture. We find a rapid transcriptomic change in infected cells, characterized by a shift to an inflammatory phenotype with upregulation of NF-κB signaling and loss of the mature alveolar program. Drug testing confirms the efficacy of remdesivir as well as TMPRSS2 protease inhibition, validating a putative mechanism used for viral entry in alveolar cells. Our model system reveals cell-intrinsic responses of a key lung target cell to SARS-CoV-2 infection and should facilitate drug development.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Alveolar Epithelial Cells
/
SARS-CoV-2
/
Inflammation
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Cell Stem Cell
Year:
2020
Document Type:
Article
Affiliation country:
J.stem.2020.09.013
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