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

Baggen, Jim; Persoons, Leentje; Vanstreels, Els; Jansen, Sander; Van Looveren, Dominique; Boeckx, Bram; Geudens, Vincent; De Man, Julie; Jochmans, Dirk; Wauters, Joost; Wauters, Els; Vanaudenaerde, Bart M; Lambrechts, Diether; Neyts, Johan; Dallmeier, Kai; Thibaut, Hendrik Jan; Jacquemyn, Maarten; Maes, Piet; Daelemans, Dirk

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.