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Bidirectional genome-wide CRISPR screens reveal host factors regulating SARS-CoV-2, MERS-CoV and seasonal HCoVs.
Rebendenne, Antoine; Roy, Priyanka; Bonaventure, Boris; Chaves Valadão, Ana Luiza; Desmarets, Lowiese; Arnaud-Arnould, Mary; Rouillé, Yves; Tauziet, Marine; Giovannini, Donatella; Touhami, Jawida; Lee, Yenarae; DeWeirdt, Peter; Hegde, Mudra; Urbach, Serge; Koulali, Khadija El; de Gracia, Francisco Garcia; McKellar, Joe; Dubuisson, Jean; Wencker, Mélanie; Belouzard, Sandrine; Moncorgé, Olivier; Doench, John G; Goujon, Caroline.
Afiliación
  • Rebendenne A; IRIM, CNRS, Montpellier University, Montpellier, France.
  • Roy P; Genetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Bonaventure B; IRIM, CNRS, Montpellier University, Montpellier, France.
  • Chaves Valadão AL; IRIM, CNRS, Montpellier University, Montpellier, France.
  • Desmarets L; Lille University, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, Lille, France.
  • Arnaud-Arnould M; IRIM, CNRS, Montpellier University, Montpellier, France.
  • Rouillé Y; Lille University, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, Lille, France.
  • Tauziet M; IRIM, CNRS, Montpellier University, Montpellier, France.
  • Giovannini D; IGMM, CNRS, Montpellier University, Montpellier, France.
  • Touhami J; Metafora Biosystems, Paris, France.
  • Lee Y; IGMM, CNRS, Montpellier University, Montpellier, France.
  • DeWeirdt P; Laboratory of Excellence GR-Ex, Paris, France.
  • Hegde M; Genetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Urbach S; Genetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Koulali KE; Genetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • de Gracia FG; IGF, Montpellier University, CNRS, INSERM, Montpellier, France.
  • McKellar J; BCM, Montpellier University, CNRS, INSERM, Montpellier, France.
  • Dubuisson J; IRIM, CNRS, Montpellier University, Montpellier, France.
  • Wencker M; IRIM, CNRS, Montpellier University, Montpellier, France.
  • Belouzard S; Lille University, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, Lille, France.
  • Moncorgé O; CIRI, INSERM, CNRS, ENS-Lyon, Lyon University, Lyon, France.
  • Doench JG; Lille University, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, Lille, France.
  • Goujon C; IRIM, CNRS, Montpellier University, Montpellier, France.
Nat Genet ; 54(8): 1090-1102, 2022 08.
Article en En | MEDLINE | ID: mdl-35879413
CRISPR knockout (KO) screens have identified host factors regulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication. Here, we conducted a meta-analysis of these screens, which showed a high level of cell-type specificity of the identified hits, highlighting the necessity of additional models to uncover the full landscape of host factors. Thus, we performed genome-wide KO and activation screens in Calu-3 lung cells and KO screens in Caco-2 colorectal cells, followed by secondary screens in four human cell lines. This revealed host-dependency factors, including AP1G1 adaptin and ATP8B1 flippase, as well as inhibitors, including mucins. Interestingly, some of the identified genes also modulate Middle East respiratory syndrome coronavirus (MERS-CoV) and seasonal human coronavirus (HCoV) (HCoV-NL63 and HCoV-229E) replication. Moreover, most genes had an impact on viral entry, with AP1G1 likely regulating TMPRSS2 activity at the plasma membrane. These results demonstrate the value of multiple cell models and perturbational modalities for understanding SARS-CoV-2 replication and provide a list of potential targets for therapeutic interventions.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Coronavirus del Síndrome Respiratorio de Oriente Medio / COVID-19 Tipo de estudio: Prognostic_studies / Systematic_reviews Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2022 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Coronavirus del Síndrome Respiratorio de Oriente Medio / COVID-19 Tipo de estudio: Prognostic_studies / Systematic_reviews Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2022 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos