Genome-Scale Identification of SARS-CoV-2 and Pan-coronavirus Host Factor Networks

  • Cell. 2021 Jan 7;184(1):120-132.e14. doi: 10.1016/j.cell.2020.12.006.
William M Schneider  1 ,  Joseph M Luna  1 ,  H-Heinrich Hoffmann  1 ,  Francisco J Sánchez-Rivera  2 ,  Andrew A Leal  3 ,  Alison W Ashbrook  1 ,  Jérémie Le Pen  1 ,  Inna Ricardo-Lax  1 ,  Eleftherios Michailidis  1 ,  Avery Peace  1 ,  Ansgar F Stenzel  4 ,  Scott W Lowe  2 ,  Margaret R MacDonald  1 ,  Charles M Rice  5 ,  John T Poirier  6
Affiliations
  • 1. Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
  • 2. Cancer Biology and Genetics, MSKCC, New York, NY 10065, USA.
  • 3. Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, NYU Langone Health, New York, NY 10016, USA.
  • 4. Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA; Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
  • 5. Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA. Electronic address: [email protected].
  • 6. Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, NYU Langone Health, New York, NY 10016, USA. Electronic address: [email protected].
PMID: 33382968 DOI: 10.1016/j.cell.2020.12.006
Abstract

The coronavirus disease 2019 (COVID-19) pandemic has claimed the lives of over one million people worldwide. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a member of the Coronaviridae family of viruses that can cause respiratory infections of varying severity. The cellular host factors and pathways co-opted during SARS-CoV-2 and related coronavirus life cycles remain ill defined. To address this gap, we performed genome-scale CRISPR knockout screens during Infection by SARS-CoV-2 and three seasonal coronaviruses (HCoV-OC43, HCoV-NL63, and HCoV-229E). These screens uncovered host factors and pathways with pan-coronavirus and virus-specific functional roles, including major dependency on glycosaminoglycan biosynthesis, sterol regulatory element-binding protein (SREBP) signaling, bone morphogenetic protein (BMP) signaling, and glycosylphosphatidylinositol biosynthesis, as well as a requirement for several poorly characterized proteins. We identified an absolute requirement for the VMP1, TMEM41, and TMEM64 (VTT) domain-containing protein transmembrane protein 41B (TMEM41B) for Infection by SARS-CoV-2 and three seasonal coronaviruses. This human coronavirus host factor compendium represents a rich resource to develop new therapeutic strategies for acute COVID-19 and potential future coronavirus pandemics.

Keywords
COVID-19; CRISPR; HCoV-229E; HCoV-NL63; HCoV-OC43; SARS-CoV-2; TMEM41B; coronavirus; genetic screens; host factors.