SARS-CoV-2 infection of primary human lung epithelium for COVID-19 modeling and drug discovery.

Adenosine Monophosphate / analogs & derivatives Adult Aged Alanine / analogs & derivatives Alveolar Epithelial Cells / metabolism COVID-19 / metabolism Child, Preschool Drug Discovery / methods Epithelial Cells / virology Epithelium / metabolism Female Fibroblasts / cytology Humans Lung / pathology Male Middle Aged Models, Biological Primary Cell Culture Respiratory Mucosa / virology SARS-CoV-2 / drug effects Virus Replication / drug effects COVID-19 Drug Treatment
COVID-19 SARS-CoV-2 adult lung epithelium alveolar type 2 cells alveoli drug discovery interferon primary in vitro model remdesivir

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
04 05 2021
Historique:
received: 05 08 2020
revised: 09 11 2020
accepted: 08 04 2021
pubmed: 28 4 2021
medline: 15 5 2021
entrez: 27 4 2021
Statut: ppublish

Résumé

Coronavirus disease 2019 (COVID-19) is the latest respiratory pandemic caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). Although infection initiates in the proximal airways, severe and sometimes fatal symptoms of the disease are caused by infection of the alveolar type 2 (AT2) cells of the distal lung and associated inflammation. In this study, we develop primary human lung epithelial infection models to understand initial responses of proximal and distal lung epithelium to SARS-CoV-2 infection. Differentiated air-liquid interface (ALI) cultures of proximal airway epithelium and alveosphere cultures of distal lung AT2 cells are readily infected by SARS-CoV-2, leading to an epithelial cell-autonomous proinflammatory response with increased expression of interferon signaling genes. Studies to validate the efficacy of selected candidate COVID-19 drugs confirm that remdesivir strongly suppresses viral infection/replication. We provide a relevant platform for study of COVID-19 pathobiology and for rapid drug screening against SARS-CoV-2 and emergent respiratory pathogens.

Identifiants

DOI: 10.1016/j.celrep.2021.109055 PMID: 33905739 PMC: PMC8043574
pubmed: 33905739
pii: S2211-1247(21)00371-5
doi: 10.1016/j.celrep.2021.109055
pmc: PMC8043574
pii:
doi:

Substances chimiques

remdesivir 3QKI37EEHE
Adenosine Monophosphate 415SHH325A
Alanine OF5P57N2ZX

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

109055

Subventions

Organisme : NIAID NIH HHS
ID : U19 AI125357
Pays : United States

Commentaires et corrections

Type : UpdateOf

Informations de copyright

Copyright © 2021. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

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Auteurs

Apoorva Mulay (A)

Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Bindu Konda (B)

Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Gustavo Garcia (G)

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA.

Changfu Yao (C)

Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Stephen Beil (S)

Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Jaquelyn M Villalba (JM)

Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; California State University, Long Beach, CA, USA.

Colin Koziol (C)

Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Chandani Sen (C)

UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.

Arunima Purkayastha (A)

UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.

Jay K Kolls (JK)

Tulane School of Medicine, New Orleans, LA 70112, USA.

Derek A Pociask (DA)

Tulane School of Medicine, New Orleans, LA 70112, USA.

Patrizia Pessina (P)

Stem Cell Program and Divisions of Hematology/Oncology and Pulmonary & Respiratory Diseases, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

Julio Sainz de Aja (JS)

Stem Cell Program and Divisions of Hematology/Oncology and Pulmonary & Respiratory Diseases, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

Carolina Garcia-de-Alba (C)

Stem Cell Program and Divisions of Hematology/Oncology and Pulmonary & Respiratory Diseases, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

Carla F Kim (CF)

Stem Cell Program and Divisions of Hematology/Oncology and Pulmonary & Respiratory Diseases, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

Brigitte Gomperts (B)

UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA; Eli and Edythe Broad, Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA.

Vaithilingaraja Arumugaswami (V)

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA; Eli and Edythe Broad, Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA. Electronic address: varumugaswami@mednet.ucla.edu.

Barry R Stripp (BR)

Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Electronic address: barry.stripp@cshs.org.

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Classifications MeSH

questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléotides › Ribonucléotides › Nucléotides adényliques › AMP › SARS-CoV-2 infection of primary human lung...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › SARS-CoV-2 infection of primary human lung...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › SARS-CoV-2 infection of primary human lung...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Alanine › SARS-CoV-2 infection of primary human lung...
questionsmedicales.fr › Cellules › Cellules épithéliales › Pneumocytes › SARS-CoV-2 infection of primary human lung...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › SARS-CoV-2 infection of primary human lung...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Enfant d'âge préscolaire › SARS-CoV-2 infection of primary human lung...
questionsmedicales.fr › Techniques d'investigation › Développement de médicament › Découverte de médicament › SARS-CoV-2 infection of primary human lung...
questionsmedicales.fr › Cellules › Cellules épithéliales › SARS-CoV-2 infection of primary human lung...
questionsmedicales.fr › Tissus › Épithélium › SARS-CoV-2 infection of primary human lung...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Fibroblastes › SARS-CoV-2 infection of primary human lung...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › SARS-CoV-2 infection of primary human lung...
questionsmedicales.fr › Appareil respiratoire › Poumon › SARS-CoV-2 infection of primary human lung...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › SARS-CoV-2 infection of primary human lung...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › SARS-CoV-2 infection of primary human lung...
questionsmedicales.fr › Techniques d'investigation › Techniques in vitro › Techniques de culture › Techniques de culture cellulaire › Culture de cellules primaires › SARS-CoV-2 infection of primary human lung...
questionsmedicales.fr › Tissus › Membranes › Muqueuse › Muqueuse respiratoire › SARS-CoV-2 infection of primary human lung...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Virus du SRAS › SARS-CoV-2 › SARS-CoV-2 infection of primary human lung...
questionsmedicales.fr › Phénomènes microbiologiques › Phénomènes physiologiques viraux › Réplication virale › SARS-CoV-2 infection of primary human lung...
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Traitements médicamenteux de la COVID-19 › SARS-CoV-2 infection of primary human lung...