Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection
| Autor: | Mia Madel Alfajaro, Victor Gasque, Huacui Chen, Madeleine C. Mankowski, David van Dijk, Kasopefoluwa Y. Oguntuyo, William J. Lu-Culligan, Jennifer S. Chen, John G. Doench, Fernando J. de Miguel, Madison S. Strine, Qin Yan, Cigall Kadoch, Cameron O. Schmitz, Robert C. Orchard, Brett D. Lindenbach, Benhur Lee, Vincent R. Graziano, Yulia V. Surovtseva, Ajinkya Patil, Renata B. Filler, Matthew D. Simon, Shang Min Zhang, Jin Wei, Craig B. Wilen, Ruth E Hanna, Wesley L. Cai, Peter C DeWeirdt, Laura Abriola, Katerina Politi, Neal G. Ravindra |
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| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Innate immune system biology viruses fungi virus diseases medicine.disease_cause medicine.disease biology.organism_classification Virology General Biochemistry Genetics and Molecular Biology Chromatin remodeling respiratory tract diseases 03 medical and health sciences 0302 clinical medicine Vesicular stomatitis virus medicine CRISPR Middle East respiratory syndrome Epigenetics skin and connective tissue diseases Gene 030217 neurology & neurosurgery 030304 developmental biology Coronavirus |
| Zdroj: | Cell |
| ISSN: | 0092-8674 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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