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Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection.
Wei, Jin; Alfajaro, Mia Madel; DeWeirdt, Peter C; Hanna, Ruth E; Lu-Culligan, William J; Cai, Wesley L; Strine, Madison S; Zhang, Shang-Min; Graziano, Vincent R; Schmitz, Cameron O; Chen, Jennifer S; Mankowski, Madeleine C; Filler, Renata B; Ravindra, Neal G; Gasque, Victor; de Miguel, Fernando J; Patil, Ajinkya; Chen, Huacui; Oguntuyo, Kasopefoluwa Y; Abriola, Laura; Surovtseva, Yulia V; Orchard, Robert C; Lee, Benhur; Lindenbach, Brett D; Politi, Katerina; van Dijk, David; Kadoch, Cigall; Simon, Matthew D; Yan, Qin; Doench, John G; Wilen, Craig B.
  • Wei J; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
  • Alfajaro MM; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
  • DeWeirdt PC; Genetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Hanna RE; Genetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Lu-Culligan WJ; Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT 06520, USA; Department of Cell Biology, Yale University, New Haven, CT 06520, USA; Chemical Biology Institute, Yale University, West Haven, CT 06516, USA.
  • Cai WL; Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
  • Strine MS; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
  • Zhang SM; Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
  • Graziano VR; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
  • Schmitz CO; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
  • Chen JS; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
  • Mankowski MC; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
  • Filler RB; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
  • Ravindra NG; Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Computer Science, Yale University, New Haven, CT 06520, USA.
  • Gasque V; Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Computer Science, Yale University, New Haven, CT 06520, USA.
  • de Miguel FJ; Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA; Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA.
  • Patil A; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Chen H; Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
  • Oguntuyo KY; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Abriola L; Yale Center for Molecular Discovery, Yale University, West Haven, CT 06516, USA.
  • Surovtseva YV; Yale Center for Molecular Discovery, Yale University, West Haven, CT 06516, USA.
  • Orchard RC; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Lee B; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Lindenbach BD; Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06520, USA.
  • Politi K; Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA; Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA; Department of Medicine, Yale School of Medicine, New Haven, CT 06520, USA.
  • van Dijk D; Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Computer Science, Yale University, New Haven, CT 06520, USA.
  • Kadoch C; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Simon MD; Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT 06520, USA; Chemical Biology Institute, Yale University, West Haven, CT 06516, USA.
  • Yan Q; Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA; Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA.
  • Doench JG; Genetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: jdoench@broadinstitute.org.
  • Wilen CB; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA; Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: craig.wilen@yale.edu.
Cell ; 184(1): 76-91.e13, 2021 01 07.
Article in English | MEDLINE | ID: covidwho-1064906
ABSTRACT
Identification of host genes essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may reveal novel therapeutic targets and inform our understanding of coronavirus disease 2019 (COVID-19) pathogenesis. Here we performed genome-wide CRISPR screens in Vero-E6 cells with SARS-CoV-2, Middle East respiratory syndrome CoV (MERS-CoV), bat CoV HKU5 expressing the SARS-CoV-1 spike, and vesicular stomatitis virus (VSV) expressing the SARS-CoV-2 spike. We identified known SARS-CoV-2 host factors, including the receptor ACE2 and protease Cathepsin L. We additionally discovered pro-viral genes and pathways, including HMGB1 and the SWI/SNF chromatin remodeling complex, that are SARS lineage and pan-coronavirus specific, respectively. We show that HMGB1 regulates ACE2 expression and is critical for entry of SARS-CoV-2, SARS-CoV-1, and NL63. We also show that small-molecule antagonists of identified gene products inhibited SARS-CoV-2 infection in monkey and human cells, demonstrating the conserved role of these genetic hits across species. This identifies potential therapeutic targets for SARS-CoV-2 and reveals SARS lineage-specific and pan-CoV host factors that regulate susceptibility to highly pathogenic CoVs.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Coronavirus Infections / Host-Pathogen Interactions / Genome-Wide Association Study / SARS-CoV-2 Limits: Animals / Humans Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2020.10.028

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Coronavirus Infections / Host-Pathogen Interactions / Genome-Wide Association Study / SARS-CoV-2 Limits: Animals / Humans Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2020.10.028