tetano
Editor, Senior Moderator
Nat Genet
. 2021 Mar 8.
doi: 10.1038/s41588-021-00805-2. Online ahead of print.
Genome-wide CRISPR screening identifies TMEM106B as a proviral host factor for SARS-CoV-2
Jim Baggen[SUP] 1 [/SUP], Leentje Persoons[SUP] #[/SUP][SUP] 2 [/SUP], Els Vanstreels[SUP] #[/SUP][SUP] 2 [/SUP], Sander Jansen[SUP] #[/SUP][SUP] 2 [/SUP], Dominique Van Looveren[SUP] 2 3 [/SUP], Bram Boeckx[SUP] 4 5 [/SUP], Vincent Geudens[SUP] 6 [/SUP], Julie De Man[SUP] 2 [/SUP], Dirk Jochmans[SUP] 2 [/SUP], Joost Wauters[SUP] 7 [/SUP], Els Wauters[SUP] 6 [/SUP], Bart M Vanaudenaerde[SUP] 6 [/SUP], Diether Lambrechts[SUP] 4 5 [/SUP], Johan Neyts[SUP] 2 [/SUP], Kai Dallmeier[SUP] 2 [/SUP], Hendrik Jan Thibaut[SUP] 2 3 [/SUP], Maarten Jacquemyn[SUP] 2 [/SUP], Piet Maes[SUP] 8 [/SUP], Dirk Daelemans[SUP] 9 [/SUP]
Affiliations
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.
. 2021 Mar 8.
doi: 10.1038/s41588-021-00805-2. Online ahead of print.
Genome-wide CRISPR screening identifies TMEM106B as a proviral host factor for SARS-CoV-2
Jim Baggen[SUP] 1 [/SUP], Leentje Persoons[SUP] #[/SUP][SUP] 2 [/SUP], Els Vanstreels[SUP] #[/SUP][SUP] 2 [/SUP], Sander Jansen[SUP] #[/SUP][SUP] 2 [/SUP], Dominique Van Looveren[SUP] 2 3 [/SUP], Bram Boeckx[SUP] 4 5 [/SUP], Vincent Geudens[SUP] 6 [/SUP], Julie De Man[SUP] 2 [/SUP], Dirk Jochmans[SUP] 2 [/SUP], Joost Wauters[SUP] 7 [/SUP], Els Wauters[SUP] 6 [/SUP], Bart M Vanaudenaerde[SUP] 6 [/SUP], Diether Lambrechts[SUP] 4 5 [/SUP], Johan Neyts[SUP] 2 [/SUP], Kai Dallmeier[SUP] 2 [/SUP], Hendrik Jan Thibaut[SUP] 2 3 [/SUP], Maarten Jacquemyn[SUP] 2 [/SUP], Piet Maes[SUP] 8 [/SUP], Dirk Daelemans[SUP] 9 [/SUP]
Affiliations
- 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.