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SARS-CoV-2 infection of primary human lung epithelium for COVID-19 modeling and drug discovery.
Mulay, Apoorva; Konda, Bindu; Garcia, Gustavo; Yao, Changfu; Beil, Stephen; Villalba, Jaquelyn M; Koziol, Colin; Sen, Chandani; Purkayastha, Arunima; Kolls, Jay K; Pociask, Derek A; Pessina, Patrizia; de Aja, Julio Sainz; Garcia-de-Alba, Carolina; Kim, Carla F; Gomperts, Brigitte; Arumugaswami, Vaithilingaraja; Stripp, Barry R.
  • Mulay A; Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Konda B; Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Garcia G; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA.
  • Yao C; Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Beil S; Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Villalba JM; Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; California State University, Long Beach, CA, USA.
  • Koziol C; Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • 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.
  • 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.
  • Kolls JK; Tulane School of Medicine, New Orleans, LA 70112, USA.
  • Pociask DA; Tulane School of Medicine, New Orleans, LA 70112, USA.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 Medici
  • 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.
  • Stripp BR; Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Electronic address: barry.stripp@cshs.org.
Cell Rep ; 35(5): 109055, 2021 05 04.
Article in English | MEDLINE | ID: covidwho-1179291
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Alveolar Epithelial Cells / SARS-CoV-2 / COVID-19 / COVID-19 Drug Treatment / Lung Type of study: Prognostic study Limits: Adult / Aged / Child, preschool / Female / Humans / Male / Middle aged Language: English Journal: Cell Rep Year: 2021 Document Type: Article Affiliation country: J.celrep.2021.109055

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Alveolar Epithelial Cells / SARS-CoV-2 / COVID-19 / COVID-19 Drug Treatment / Lung Type of study: Prognostic study Limits: Adult / Aged / Child, preschool / Female / Humans / Male / Middle aged Language: English Journal: Cell Rep Year: 2021 Document Type: Article Affiliation country: J.celrep.2021.109055