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Genome-wide bidirectional CRISPR screens identify mucins as host factors modulating SARS-CoV-2 infection.
Biering, Scott B; Sarnik, Sylvia A; Wang, Eleanor; Zengel, James R; Leist, Sarah R; Schäfer, Alexandra; Sathyan, Varun; Hawkins, Padraig; Okuda, Kenichi; Tau, Cyrus; Jangid, Aditya R; Duffy, Connor V; Wei, Jin; Gilmore, Rodney C; Alfajaro, Mia Madel; Strine, Madison S; Nguyenla, Xammy; Van Dis, Erik; Catamura, Carmelle; Yamashiro, Livia H; Belk, Julia A; Begeman, Adam; Stark, Jessica C; Shon, D Judy; Fox, Douglas M; Ezzatpour, Shahrzad; Huang, Emily; Olegario, Nico; Rustagi, Arjun; Volmer, Allison S; Livraghi-Butrico, Alessandra; Wehri, Eddie; Behringer, Richard R; Cheon, Dong-Joo; Schaletzky, Julia; Aguilar, Hector C; Puschnik, Andreas S; Button, Brian; Pinsky, Benjamin A; Blish, Catherine A; Baric, Ralph S; O'Neal, Wanda K; Bertozzi, Carolyn R; Wilen, Craig B; Boucher, Richard C; Carette, Jan E; Stanley, Sarah A; Harris, Eva; Konermann, Silvana; Hsu, Patrick D.
  • Biering SB; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
  • Sarnik SA; Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
  • Wang E; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
  • Zengel JR; Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
  • Leist SR; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
  • Schäfer A; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
  • Sathyan V; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Hawkins P; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Okuda K; Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
  • Tau C; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
  • Jangid AR; Marsico Lung Institute and Cystic Fibrosis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Duffy CV; Marsico Lung Institute and Cystic Fibrosis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Wei J; Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
  • Gilmore RC; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
  • Alfajaro MM; Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
  • Strine MS; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
  • Nguyenla X; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.
  • Van Dis E; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA.
  • Catamura C; Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
  • Yamashiro LH; Marsico Lung Institute and Cystic Fibrosis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Belk JA; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA.
  • Begeman A; Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
  • Stark JC; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA.
  • Shon DJ; Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
  • Fox DM; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
  • Ezzatpour S; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
  • Huang E; Center for Computational Biology, University of California, Berkeley, Berkeley, CA, USA.
  • Olegario N; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
  • Rustagi A; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
  • Volmer AS; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.
  • Livraghi-Butrico A; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
  • Wehri E; Department of Chemistry and Stanford ChEM-H, Stanford University, Stanford, CA, USA.
  • Behringer RR; Department of Chemistry and Stanford ChEM-H, Stanford University, Stanford, CA, USA.
  • Cheon DJ; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
  • Schaletzky J; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
  • Aguilar HC; Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
  • Puschnik AS; Marsico Lung Institute and Cystic Fibrosis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Button B; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Pinsky BA; Marsico Lung Institute and Cystic Fibrosis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Blish CA; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Baric RS; Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • O'Neal WK; Marsico Lung Institute and Cystic Fibrosis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Bertozzi CR; Marsico Lung Institute and Cystic Fibrosis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Wilen CB; The Henry Wheeler Center for Emerging and Neglected Diseases, Berkeley, CA, USA.
  • Boucher RC; Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Carette JE; Department of Regenerative and Cancer Cell Biology, Albany Medical College, Albany, NY, USA.
  • Stanley SA; The Henry Wheeler Center for Emerging and Neglected Diseases, Berkeley, CA, USA.
  • Harris E; Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
  • Konermann S; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Hsu PD; Marsico Lung Institute and Cystic Fibrosis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Nat Genet ; 54(8): 1078-1089, 2022 08.
Article in English | MEDLINE | ID: covidwho-1960394
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a range of symptoms in infected individuals, from mild respiratory illness to acute respiratory distress syndrome. A systematic understanding of host factors influencing viral infection is critical to elucidate SARS-CoV-2-host interactions and the progression of Coronavirus disease 2019 (COVID-19). Here, we conducted genome-wide CRISPR knockout and activation screens in human lung epithelial cells with endogenous expression of the SARS-CoV-2 entry factors ACE2 and TMPRSS2. We uncovered proviral and antiviral factors across highly interconnected host pathways, including clathrin transport, inflammatory signaling, cell-cycle regulation, and transcriptional and epigenetic regulation. We further identified mucins, a family of high molecular weight glycoproteins, as a prominent viral restriction network that inhibits SARS-CoV-2 infection in vitro and in murine models. These mucins also inhibit infection of diverse respiratory viruses. This functional landscape of SARS-CoV-2 host factors provides a physiologically relevant starting point for new host-directed therapeutics and highlights airway mucins as a host defense mechanism.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Systematic review/Meta Analysis Limits: Animals / Humans Language: English Journal: Nat Genet Journal subject: Genetics, Medical Year: 2022 Document Type: Article Affiliation country: S41588-022-01131-x

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Systematic review/Meta Analysis Limits: Animals / Humans Language: English Journal: Nat Genet Journal subject: Genetics, Medical Year: 2022 Document Type: Article Affiliation country: S41588-022-01131-x