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Survival-based CRISPR genetic screens across a panel of permissive cell lines identify common and cell-specific SARS-CoV-2 host factors.
Chan, Katherine; Farias, Adrian Granda; Lee, Hunsang; Guvenc, Furkan; Mero, Patricia; Brown, Kevin R; Ward, Henry; Billmann, Maximilian; Aulakh, Kamaldeep; Astori, Audrey; Haider, Shahan; Marcon, Edyta; Braunschweig, Ulrich; Pu, Shuye; Habsid, Andrea; Yan Tong, Amy Hin; Christie-Holmes, Natasha; Budylowski, Patrick; Ghalami, Ayoob; Mubareka, Samira; Maguire, Finlay; Banerjee, Arinjay; Mossman, Karen L; Greenblatt, Jack; Gray-Owen, Scott D; Raught, Brian; Blencowe, Benjamin J; Taipale, Mikko; Myers, Chad; Moffat, Jason.
  • Chan K; Donnelly Center, 160 College Street, University of Toronto, Toronto, Ontario, Canada, M5S3E1.
  • Farias AG; Donnelly Center, 160 College Street, University of Toronto, Toronto, Ontario, Canada, M5S3E1.
  • Lee H; Department of Molecular Genetics, 1 King's College Circle, University of Toronto, Toronto, Ontario, Canada, M5S1A8.
  • Guvenc F; Donnelly Center, 160 College Street, University of Toronto, Toronto, Ontario, Canada, M5S3E1.
  • Mero P; Department of Molecular Genetics, 1 King's College Circle, University of Toronto, Toronto, Ontario, Canada, M5S1A8.
  • Brown KR; Donnelly Center, 160 College Street, University of Toronto, Toronto, Ontario, Canada, M5S3E1.
  • Ward H; Donnelly Center, 160 College Street, University of Toronto, Toronto, Ontario, Canada, M5S3E1.
  • Billmann M; Department of Computer Science and Engineering, University of Minnesota-Twin Cities, Minneapolis, MN, USA.
  • Aulakh K; Department of Computer Science and Engineering, University of Minnesota-Twin Cities, Minneapolis, MN, USA.
  • Astori A; Donnelly Center, 160 College Street, University of Toronto, Toronto, Ontario, Canada, M5S3E1.
  • Haider S; Princess Margaret Cancer Center, Toronto, Ontario, Canada.
  • Marcon E; Donnelly Center, 160 College Street, University of Toronto, Toronto, Ontario, Canada, M5S3E1.
  • Braunschweig U; Donnelly Center, 160 College Street, University of Toronto, Toronto, Ontario, Canada, M5S3E1.
  • Pu S; Donnelly Center, 160 College Street, University of Toronto, Toronto, Ontario, Canada, M5S3E1.
  • Habsid A; Donnelly Center, 160 College Street, University of Toronto, Toronto, Ontario, Canada, M5S3E1.
  • Yan Tong AH; Donnelly Center, 160 College Street, University of Toronto, Toronto, Ontario, Canada, M5S3E1.
  • Christie-Holmes N; Donnelly Center, 160 College Street, University of Toronto, Toronto, Ontario, Canada, M5S3E1.
  • Budylowski P; Combined Containment Level 3 Unit, Temerty Faculty of Medicine, University of Toronto Toronto, Ontario, Canada, M5S3E1.
  • Ghalami A; Department of Molecular Genetics, 1 King's College Circle, University of Toronto, Toronto, Ontario, Canada, M5S1A8.
  • Mubareka S; Office of Environmental Health & Safety, University of Toronto, Toronto, Ontario, Canada.
  • Maguire F; Sunnybrook Research Institute, Toronto, Ontario, Canada, M5S3E1.
  • Banerjee A; Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada.
  • Mossman KL; Department of Community Health and Epidemiology, Faculty of Medicine Dalhousie University, Halifax, Nova Scotia, Canada.
  • Greenblatt J; Faculty of Computer Science, Dalhousie University, Halifax, Nova Scotia, Canada.
  • Gray-Owen SD; Vaccine and Infectious Disease Organization, Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
  • Raught B; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
  • Blencowe BJ; Donnelly Center, 160 College Street, University of Toronto, Toronto, Ontario, Canada, M5S3E1.
  • Taipale M; Department of Molecular Genetics, 1 King's College Circle, University of Toronto, Toronto, Ontario, Canada, M5S1A8.
  • Myers C; Department of Molecular Genetics, 1 King's College Circle, University of Toronto, Toronto, Ontario, Canada, M5S1A8.
  • Moffat J; Princess Margaret Cancer Center, Toronto, Ontario, Canada.
Heliyon ; 9(1): e12744, 2023 Jan.
Article in English | MEDLINE | ID: covidwho-2165334
ABSTRACT
SARS-CoV-2 depends on host cell components for infection and replication. Identification of virus-host dependencies offers an effective way to elucidate mechanisms involved in viral infection and replication. If druggable, host factor dependencies may present an attractive strategy for anti-viral therapy. In this study, we performed genome wide CRISPR knockout screens in Vero E6 cells and four human cell lines including Calu-3, UM-UC-4, HEK-293 and HuH-7 to identify genetic regulators of SARS-CoV-2 infection. Our findings identified only ACE2, the cognate SARS-CoV-2 entry receptor, as a common host dependency factor across all cell lines, while other host genes identified were largely cell line specific, including known factors TMPRSS2 and CTSL. Several of the discovered host-dependency factors converged on pathways involved in cell signalling, immune-related pathways, and chromatin modification. Notably, the chromatin modifier gene KMT2C in Calu-3 cells had the strongest impact in preventing SARS-CoV-2 infection when perturbed.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Journal: Heliyon Year: 2023 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Journal: Heliyon Year: 2023 Document Type: Article