About: SARS-CoV-2 Infection of Pluripotent Stem Cell-derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response

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About: SARS-CoV-2 Infection of Pluripotent Stem Cell-derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	SARS-CoV-2 Infection of Pluripotent Stem Cell-derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response
Creator	Mühlberger, Elke Bullitt, Esther Olejnik, Judith Wilson, Andrew Saeed, Mohsan Hume, Adam Kotton, Darrell Wang, Ruobing Abo, Kristine Alysandratos, Konstantinos-Dionysios Beermann, Mary Bosmann, Markus Burks, Eric Hawkins, Finn Hinds, Anne Huang, Jessie Lindstrom-Vautrin, Jonathan Sharma, Arjun Simone-Roach, Chantelle Suder, Ellen Villacorta-Martin, Carlos Werder, Rhiannon
source	BioRxiv; Medline; PMC
abstract	The most severe and fatal infections with SARS-CoV-2 result in the acute respiratory distress syndrome, a clinical phenotype of coronavirus disease 2019 (COVID-19) that is associated with virions targeting the epithelium of the distal lung, particularly the facultative progenitors of this tissue, alveolar epithelial type 2 cells (AT2s). Little is known about the initial responses of human lung alveoli to SARS-CoV-2 infection due in part to inability to access these cells from patients, particularly at early stages of disease. Here we present an in vitro human model that simulates the initial apical infection of the distal lung epithelium with SARS-CoV-2, using AT2s that have been adapted to air-liquid interface culture after their derivation from induced pluripotent stem cells (iAT2s). We find that SARS-CoV-2 induces a rapid global transcriptomic change in infected iAT2s characterized by a shift to an inflammatory phenotype predominated by the secretion of cytokines encoded by NF-kB target genes, delayed epithelial interferon responses, and rapid loss of the mature lung alveolar epithelial program. Over time, infected iAT2s exhibit cellular toxicity that can result in the death of these key alveolar facultative progenitors, as is observed in vivo in COVID-19 lung autopsies. Importantly, drug testing using iAT2s confirmed the efficacy of TMPRSS2 protease inhibition, validating putative mechanisms used for viral entry in human alveolar cells. Our model system reveals the cell-intrinsic responses of a key lung target cell to infection, providing a platform for further drug development and facilitating a deeper understanding of COVID-19 pathogenesis.
has issue date	2020-06-30(xsd:dateTime)
bibo:doi	10.1101/2020.06.30.175695
bibo:pmid	32637964
has license	cc-by-nc-nd
sha1sum (hex)	d707448a4cbee9e5a79c5b4805f58fa887a3d8eb
schema:url	https://doi.org/10.1101/2020.06.30.175695
resource representing a document's title	SARS-CoV-2 Infection of Pluripotent Stem Cell-derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response
has PubMed Central identifier	PMC7337394
has PubMed identifier	32637964
schema:publication	bioRxiv
resource representing a document's body	covid:d707448a4cbee9e5a79c5b4805f58fa887a3d8eb#body_text
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