tetano
Editor, Senior Moderator
Cell
. 2020 Oct 20;S0092-8674(20)31392-1.
doi: 10.1016/j.cell.2020.10.028. Online ahead of print.
Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection
Jin Wei[SUP] 1 [/SUP], Mia Madel Alfajaro[SUP] 1 [/SUP], Peter C DeWeirdt[SUP] 2 [/SUP], Ruth E Hanna[SUP] 2 [/SUP], William J Lu-Culligan[SUP] 3 [/SUP], Wesley L Cai[SUP] 4 [/SUP], Madison S Strine[SUP] 1 [/SUP], Shang-Min Zhang[SUP] 4 [/SUP], Vincent R Graziano[SUP] 1 [/SUP], Cameron O Schmitz[SUP] 1 [/SUP], Jennifer S Chen[SUP] 1 [/SUP], Madeleine C Mankowski[SUP] 1 [/SUP], Renata B Filler[SUP] 1 [/SUP], Neal G Ravindra[SUP] 5 [/SUP], Victor Gasque[SUP] 5 [/SUP], Fernando J de Miguel[SUP] 6 [/SUP], Ajinkya Patil[SUP] 7 [/SUP], Huacui Chen[SUP] 4 [/SUP], Kasopefoluwa Y Oguntuyo[SUP] 8 [/SUP], Laura Abriola[SUP] 9 [/SUP], Yulia V Surovtseva[SUP] 9 [/SUP], Robert C Orchard[SUP] 10 [/SUP], Benhur Lee[SUP] 8 [/SUP], Brett D Lindenbach[SUP] 11 [/SUP], Katerina Politi[SUP] 12 [/SUP], David van Dijk[SUP] 5 [/SUP], Cigall Kadoch[SUP] 7 [/SUP], Matthew D Simon[SUP] 13 [/SUP], Qin Yan[SUP] 6 [/SUP], John G Doench[SUP] 14 [/SUP], Craig B Wilen[SUP] 15 [/SUP]
Affiliations
Abstract
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.
Keywords: COVID-19; CRISPR screen; Epigenetics; HMGB1; MERS-CoV; Middle East Respiratory Syndrome; SARS-CoV-2; SWI/SNF complex; Severe Acute Respiratory Syndrome.
. 2020 Oct 20;S0092-8674(20)31392-1.
doi: 10.1016/j.cell.2020.10.028. Online ahead of print.
Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection
Jin Wei[SUP] 1 [/SUP], Mia Madel Alfajaro[SUP] 1 [/SUP], Peter C DeWeirdt[SUP] 2 [/SUP], Ruth E Hanna[SUP] 2 [/SUP], William J Lu-Culligan[SUP] 3 [/SUP], Wesley L Cai[SUP] 4 [/SUP], Madison S Strine[SUP] 1 [/SUP], Shang-Min Zhang[SUP] 4 [/SUP], Vincent R Graziano[SUP] 1 [/SUP], Cameron O Schmitz[SUP] 1 [/SUP], Jennifer S Chen[SUP] 1 [/SUP], Madeleine C Mankowski[SUP] 1 [/SUP], Renata B Filler[SUP] 1 [/SUP], Neal G Ravindra[SUP] 5 [/SUP], Victor Gasque[SUP] 5 [/SUP], Fernando J de Miguel[SUP] 6 [/SUP], Ajinkya Patil[SUP] 7 [/SUP], Huacui Chen[SUP] 4 [/SUP], Kasopefoluwa Y Oguntuyo[SUP] 8 [/SUP], Laura Abriola[SUP] 9 [/SUP], Yulia V Surovtseva[SUP] 9 [/SUP], Robert C Orchard[SUP] 10 [/SUP], Benhur Lee[SUP] 8 [/SUP], Brett D Lindenbach[SUP] 11 [/SUP], Katerina Politi[SUP] 12 [/SUP], David van Dijk[SUP] 5 [/SUP], Cigall Kadoch[SUP] 7 [/SUP], Matthew D Simon[SUP] 13 [/SUP], Qin Yan[SUP] 6 [/SUP], John G Doench[SUP] 14 [/SUP], Craig B Wilen[SUP] 15 [/SUP]
Affiliations
- PMID: 33147444
- PMCID: PMC7574718
- DOI: 10.1016/j.cell.2020.10.028
Abstract
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.
Keywords: COVID-19; CRISPR screen; Epigenetics; HMGB1; MERS-CoV; Middle East Respiratory Syndrome; SARS-CoV-2; SWI/SNF complex; Severe Acute Respiratory Syndrome.