tetano
Editor, Senior Moderator
Cell
. 2020 Dec 9;S0092-8674(20)31676-7.
doi: 10.1016/j.cell.2020.12.006. Online ahead of print.
Genome-Scale Identification of SARS-CoV-2 and Pan-coronavirus Host Factor Networks
William M Schneider[SUP] 1 [/SUP], Joseph M Luna[SUP] 1 [/SUP], H-Heinrich Hoffmann[SUP] 1 [/SUP], Francisco J S?nchez-Rivera[SUP] 2 [/SUP], Andrew A Leal[SUP] 3 [/SUP], Alison W Ashbrook[SUP] 1 [/SUP], J?r?mie Le Pen[SUP] 1 [/SUP], Inna Ricardo-Lax[SUP] 1 [/SUP], Eleftherios Michailidis[SUP] 1 [/SUP], Avery Peace[SUP] 1 [/SUP], Ansgar F Stenzel[SUP] 4 [/SUP], Scott W Lowe[SUP] 2 [/SUP], Margaret R MacDonald[SUP] 1 [/SUP], Charles M Rice[SUP] 5 [/SUP], John T Poirier[SUP] 6 [/SUP]
Affiliations
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.
. 2020 Dec 9;S0092-8674(20)31676-7.
doi: 10.1016/j.cell.2020.12.006. Online ahead of print.
Genome-Scale Identification of SARS-CoV-2 and Pan-coronavirus Host Factor Networks
William M Schneider[SUP] 1 [/SUP], Joseph M Luna[SUP] 1 [/SUP], H-Heinrich Hoffmann[SUP] 1 [/SUP], Francisco J S?nchez-Rivera[SUP] 2 [/SUP], Andrew A Leal[SUP] 3 [/SUP], Alison W Ashbrook[SUP] 1 [/SUP], J?r?mie Le Pen[SUP] 1 [/SUP], Inna Ricardo-Lax[SUP] 1 [/SUP], Eleftherios Michailidis[SUP] 1 [/SUP], Avery Peace[SUP] 1 [/SUP], Ansgar F Stenzel[SUP] 4 [/SUP], Scott W Lowe[SUP] 2 [/SUP], Margaret R MacDonald[SUP] 1 [/SUP], Charles M Rice[SUP] 5 [/SUP], John T Poirier[SUP] 6 [/SUP]
Affiliations
- 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.