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Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2.
Hekman, Ryan M; Hume, Adam J; Goel, Raghuveera Kumar; Abo, Kristine M; Huang, Jessie; Blum, Benjamin C; Werder, Rhiannon B; Suder, Ellen L; Paul, Indranil; Phanse, Sadhna; Youssef, Ahmed; Alysandratos, Konstantinos D; Padhorny, Dzmitry; Ojha, Sandeep; Mora-Martin, Alexandra; Kretov, Dmitry; Ash, Peter E A; Verma, Mamta; Zhao, Jian; Patten, J J; Villacorta-Martin, Carlos; Bolzan, Dante; Perea-Resa, Carlos; Bullitt, Esther; Hinds, Anne; Tilston-Lunel, Andrew; Varelas, Xaralabos; Farhangmehr, Shaghayegh; Braunschweig, Ulrich; Kwan, Julian H; McComb, Mark; Basu, Avik; Saeed, Mohsan; Perissi, Valentina; Burks, Eric J; Layne, Matthew D; Connor, John H; Davey, Robert; Cheng, Ji-Xin; Wolozin, Benjamin L; Blencowe, Benjamin J; Wuchty, Stefan; Lyons, Shawn M; Kozakov, Dima; Cifuentes, Daniel; Blower, Michael; Kotton, Darrell N; Wilson, Andrew A; Mühlberger, Elke; Emili, Andrew.
  • 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.
Mol Cell ; 80(6): 1104-1122.e9, 2020 12 17.
Article in English | MEDLINE | ID: covidwho-933377
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Phosphoproteins / Proteome / Alveolar Epithelial Cells / SARS-CoV-2 / COVID-19 Type of study: Observational study / Prognostic study Topics: Traditional medicine Limits: Animals / Humans Language: English Journal: Mol Cell Journal subject: Molecular Biology Year: 2020 Document Type: Article Affiliation country: J.molcel.2020.11.028

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Phosphoproteins / Proteome / Alveolar Epithelial Cells / SARS-CoV-2 / COVID-19 Type of study: Observational study / Prognostic study Topics: Traditional medicine Limits: Animals / Humans Language: English Journal: Mol Cell Journal subject: Molecular Biology Year: 2020 Document Type: Article Affiliation country: J.molcel.2020.11.028