Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection

Jin Wei, Mia Madel Alfajaro, Peter C. DeWeirdt, Ruth E. Hanna, William J. Lu-Culligan, Wesley L. Cai, Madison S. Strine, Shang Min Zhang, Vincent R. Graziano, Cameron O. Schmitz, Jennifer S. Chen, Madeleine C. Mankowski, Renata B. Filler, Neal G. Ravindra, Victor Gasque, Fernando J. de Miguel, Ajinkya Patil, Huacui Chen, Kasopefoluwa Y. Oguntuyo, Laura AbriolaYulia V. Surovtseva, Robert C. Orchard, Benhur Lee, Brett D. Lindenbach, Katerina Politi, David van Dijk, Cigall Kadoch, Matthew D. Simon, Qin Yan, John G. Doench, Craig B. Wilen

Research output: Contribution to journalArticlepeer-review

309 Scopus citations

Abstract

To identify potential therapeutic targets for SARS-CoV-2 and related pathogenic coronaviruses, Wei et al. conduct genome-wide CRISPR screens in Vero-E6 cells using SARS-CoV-2, MERS-CoV, and pseudoviruses presenting SARS-CoV-1 or SARS-CoV-2 spike proteins. They identify pro-viral genes and pathways, including HMGB1 and the SWI/SNF chromatin remodeling complex, that are SARS lineage and pan-coronavirus specific, respectively, and demonstrate that HMGB1 is critical for SARS lineage viral entry because it has a critical role in ACE2 expression.

Original languageEnglish (US)
Pages (from-to)76-91.e13
JournalCell
Volume184
Issue number1
DOIs
StatePublished - Jan 7 2021

Keywords

  • COVID-19
  • CRISPR screen
  • Epigenetics
  • HMGB1
  • MERS-CoV
  • Middle East Respiratory Syndrome
  • SARS-CoV-2
  • SWI/SNF complex
  • Severe Acute Respiratory Syndrome

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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