Bidirectional genome-wide CRISPR screens reveal host factors regulating SARS-CoV-2, MERS-CoV and seasonal HCoVs.

COVID-19 / genetics Caco-2 Cells Clustered Regularly Interspaced Short Palindromic Repeats / genetics Humans Middle East Respiratory Syndrome Coronavirus / genetics SARS-CoV-2 / genetics Seasons

Journal

Nature genetics

ISSN: 1546-1718

Titre abrégé: Nat Genet

Pays: United States

ID NLM: 9216904

Informations de publication

Date de publication:
08 2022

Historique:

received: 23 05 2021

accepted: 26 05 2022

pubmed: 26 7 2022

medline: 10 8 2022

entrez: 25 7 2022

Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1038/s41588-022-01110-2 PMID: 35879413

pubmed: 35879413

doi: 10.1038/s41588-022-01110-2

pii: 10.1038/s41588-022-01110-2

doi:

Types de publication

Journal Article Meta-Analysis Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

Pagination

1090-1102

Subventions

Organisme : NIAID NIH HHS

ID : R21 AI157835

Pays : United States

Commentaires et corrections

Type : UpdateOf

Informations de copyright

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