Genome-scale identification of SARS-CoV-2 and pan-coronavirus host factor networks Journal Article


Authors: Schneider, W. M.; Luna, J. M.; Hoffmann, H. H.; Sánchez-Rivera, F. J.; Leal, A. A.; Ashbrook, A. W.; Le Pen, J.; Ricardo-Lax, I.; Michailidis, E.; Peace, A.; Stenzel, A. F.; Lowe, S. W.; MacDonald, M. R.; Rice, C. M.; Poirier, J. T.
Article Title: Genome-scale identification of SARS-CoV-2 and pan-coronavirus host factor networks
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: protein; biosynthesis; cell-lines; binding; attachment; respiratory syncytial virus; mediator complex; entry; heparan-sulfate glycosaminoglycans; linkage region; cog complex
Journal Title: Cell
Volume: 184
Issue: 1
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2021-01-07
Start Page: 120
End Page: 132.e14
Language: English
ACCESSION: WOS:000606505400011
DOI: 10.1016/j.cell.2020.12.006
PROVIDER: wos
PMCID: PMC7796900
PUBMED: 33382968
Notes: Article -- Source: Wos
Altmetric
Citation Impact
MSK Authors
  1. Scott W Lowe
    218 Lowe