Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2.

Autor:	Hekman RM; Center for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA., Hume AJ; Department of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA., Goel RK; Center for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA., Abo KM; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA, USA; The Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA, USA., Huang J; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA, USA; The Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA, USA., Blum BC; Center for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA., Werder RB; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA, USA; The Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA, USA., Suder EL; Department of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA., Paul I; Center for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA., Phanse S; Center for Network Systems Biology, Boston University, Boston, MA, USA., Youssef A; Center for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA; Bioinformatics Program, Boston University, Boston, MA, USA., Alysandratos KD; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA, USA; The Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA, USA., Padhorny D; Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, USA; Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, NY, USA., Ojha S; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA., Mora-Martin A; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA., Kretov D; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA., Ash PEA; Department of Pharmacology, Boston University School of Medicine, Boston, MA, USA., Verma M; Department of Pharmacology, Boston University School of Medicine, Boston, MA, USA., Zhao J; Department of Electrical and Computer Engineering, Boston University, Boston, MA, USA., Patten JJ; Department of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA., Villacorta-Martin C; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA, USA., Bolzan D; Department of Computer Science, University of Miami, Miami, FL, USA., Perea-Resa C; Department of Molecular Biology, Harvard Medical School, Boston, MA, USA., Bullitt E; Department of Physiology and Biophysics, Boston University, Boston, MA, USA., Hinds A; The Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA, USA., Tilston-Lunel A; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA., Varelas X; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA., Farhangmehr S; Donnelly Centre, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada., Braunschweig U; Donnelly Centre, University of Toronto, Toronto, ON, Canada., Kwan JH; Center for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA., McComb M; Center for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA; Center for Biomedical Mass Spectrometry, Boston University School of Medicine, Boston, MA, USA., Basu A; Center for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA., Saeed M; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA., Perissi V; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA., Burks EJ; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, USA., Layne MD; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA., Connor JH; Department of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA., Davey R; Department of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA., Cheng JX; Department of Biomedical Engineering, Boston University, Boston, MA, USA., Wolozin BL; Department of Pharmacology, Boston University School of Medicine, Boston, MA, USA., Blencowe BJ; Donnelly Centre, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada., Wuchty S; Department of Computer Science, University of Miami, Miami, FL, USA; Department of Biology, University of Miami, Miami, FL, USA; Miami Institute of Data Science and Computing, Miami, FL, USA., Lyons SM; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA., Kozakov D; Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, USA; Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, NY, USA., Cifuentes D; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA., Blower M; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA; Department of Molecular Biology, Harvard Medical School, Boston, MA, USA., Kotton DN; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA, USA; The Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA, USA. Electronic address: dkotton@bu.edu., Wilson AA; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA, USA; The Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA, USA. Electronic address: awilson@bu.edu., Mühlberger E; Department of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA. Electronic address: muehlber@bu.edu., Emili A; Center for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA; Department of Biology, Boston University, Boston, MA, USA. Electronic address: aemili@bu.edu.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2020 Dec 17; Vol. 80 (6), pp. 1104-1122.e9. Date of Electronic Publication: 2020 Nov 19.
DOI:	10.1016/j.molcel.2020.11.028
Abstrakt:	Human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative pathogen of the COVID-19 pandemic, exerts a massive health and socioeconomic crisis. The virus infects alveolar epithelial type 2 cells (AT2s), leading to lung injury and impaired gas exchange, but the mechanisms driving infection and pathology are unclear. We performed a quantitative phosphoproteomic survey of induced pluripotent stem cell-derived AT2s (iAT2s) infected with SARS-CoV-2 at air-liquid interface (ALI). Time course analysis revealed rapid remodeling of diverse host systems, including signaling, RNA processing, translation, metabolism, nuclear integrity, protein trafficking, and cytoskeletal-microtubule organization, leading to cell cycle arrest, genotoxic stress, and innate immunity. Comparison to analogous data from transformed cell lines revealed respiratory-specific processes hijacked by SARS-CoV-2, highlighting potential novel therapeutic avenues that were validated by a high hit rate in a targeted small molecule screen in our iAT2 ALI system. Competing Interests: Declaration of Interests B.L.W. declares a position as CSO of Aquinnah Pharmaceuticals. A.E. and D.N.K. declare industry funding from Johnson & Johnson, Merck, and Novartis. (Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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