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Genome-wide CRISPR screening identifies TMEM106B as a proviral host factor for SARS-CoV-2. 2021
Jim Baggen, and
Leentje Persoons, and
Els Vanstreels, and
Sander Jansen, and
Dominique Van Looveren, and
Bram Boeckx, and
Vincent Geudens, and
Julie De Man, and
Dirk Jochmans, and
Joost Wauters, and
Els Wauters, and
Bart M Vanaudenaerde, and
Diether Lambrechts, and
Johan Neyts, and
Kai Dallmeier, and
Hendrik Jan Thibaut, and
Maarten Jacquemyn, and
Piet Maes, and
Dirk Daelemans
KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, Leuven, Belgium. jim.baggen@kuleuven.be.
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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