Journal
CELL
Volume 184, Issue 1, Pages 120-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2020.12.006
Keywords
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Categories
Funding
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R01AI091707]
- EMBO fellowship [ALTF 380-2018, F32AI133910]
- Robertson Foundation
- Agilent Technologies Thought Leader Award
- MSKCC Translational Research Oncology Training Fellowship [NIH T32-CA160001]
- G. Harold and Leila Y. Mathers Charitable Foundation
- BAWD Foundation
- [U19AI111825]
- [R01CA190261]
- [R01CA213448]
- [U01CA213359]
- [R01AI143295]
- [R01AI150275]
- [R01AI124690]
- [R01AI116943]
- [P01AI138938]
- [P30CA008748]
- [P30CA016087]
- [R03AI141855]
- [R21AI142010]
- [W81XWH1910409]
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The study revealed the host factors and pathways involved in SARS-CoV-2 and seasonal coronavirus infections, providing a rich resource for developing therapeutic strategies for future coronavirus pandemics.
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.
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