Genome-wide CRISPR screening identifies TMEM106B as a proviral host factor for SARS-CoV-2

  • Nat Genet. 2021 Apr;53(4):435-444. doi: 10.1038/s41588-021-00805-2.
Jim Baggen  1 ,  Leentje Persoons   #  2 ,  Els Vanstreels   #  2 ,  Sander Jansen   #  2 ,  Dominique Van Looveren  2  3 ,  Bram Boeckx  4  5 ,  Vincent Geudens  6 ,  Julie De Man  2 ,  Dirk Jochmans  2 ,  Joost Wauters  7 ,  Els Wauters  6 ,  Bart M Vanaudenaerde  6 ,  Diether Lambrechts  4  5 ,  Johan Neyts  2 ,  Kai Dallmeier  2 ,  Hendrik Jan Thibaut  2  3 ,  Maarten Jacquemyn  2 ,  Piet Maes  8 ,  Dirk Daelemans  9
Affiliations
  • 1. KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, Leuven, Belgium. [email protected].
  • 2. KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, Leuven, Belgium.
  • 3. KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Translational Platform Virology and Chemotherapy, Rega Institute, Leuven, Belgium.
  • 4. KU Leuven Department of Human Genetics, Laboratory for Translational Genetics, Leuven, Belgium.
  • 5. VIB Center for Cancer Biology, VIB, Leuven, Belgium.
  • 6. KU Leuven Department of Chronic Diseases and Metabolism, Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Leuven, Belgium.
  • 7. KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical Infectious and Inflammatory Disorders, Leuven, Belgium.
  • 8. KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical and Epidemiological Virology, Rega Institute, Leuven, Belgium.
  • 9. KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, Leuven, Belgium. [email protected].
  • # Contributed equally.
PMID: 33686287 DOI: 10.1038/s41588-021-00805-2
Abstract

The ongoing COVID-19 pandemic has caused a global economic and health crisis. To identify host factors essential for coronavirus Infection, we performed genome-wide functional genetic screens with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human coronavirus 229E. These screens uncovered virus-specific as well as shared host factors, including TMEM41B and PI3K type 3. We discovered that SARS-CoV-2 requires the lysosomal protein TMEM106B to infect human cell lines and primary lung cells. TMEM106B overexpression enhanced SARS-CoV-2 Infection as well as pseudovirus Infection, suggesting a role in viral entry. Furthermore, single-cell RNA-sequencing of airway cells from patients with COVID-19 demonstrated that TMEM106B expression correlates with SARS-CoV-2 Infection. The present study uncovered a collection of coronavirus host factors that may be exploited to develop drugs against SARS-CoV-2 Infection or future zoonotic coronavirus outbreaks.

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