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Identification of TMEM106B as proviral host factor for SARS-CoV-2

View ORCID ProfileJim Baggen, View ORCID ProfileLeentje Persoons, Sander Jansen, View ORCID ProfileEls Vanstreels, View ORCID ProfileMaarten Jacquemyn, View ORCID ProfileDirk Jochmans, View ORCID ProfileJohan Neyts, View ORCID ProfileKai Dallmeier, View ORCID ProfilePiet Maes, View ORCID ProfileDirk Daelemans
doi: https://doi.org/10.1101/2020.09.28.316281
Jim Baggen
1KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, 3000 Leuven, Belgium
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  • For correspondence: jim.baggen@kuleuven.be dirk.daelemans@kuleuven.be
Leentje Persoons
1KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, 3000 Leuven, Belgium
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Sander Jansen
1KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, 3000 Leuven, Belgium
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Els Vanstreels
1KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, 3000 Leuven, Belgium
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Maarten Jacquemyn
1KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, 3000 Leuven, Belgium
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Dirk Jochmans
1KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, 3000 Leuven, Belgium
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Johan Neyts
1KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, 3000 Leuven, Belgium
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Kai Dallmeier
1KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, 3000 Leuven, Belgium
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Piet Maes
2KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical and Epidemiological Virology, Rega Institute, 3000 Leuven, Belgium
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Dirk Daelemans
1KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, 3000 Leuven, Belgium
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  • For correspondence: jim.baggen@kuleuven.be dirk.daelemans@kuleuven.be
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SUMMARY

The ongoing COVID-19 pandemic is responsible for worldwide economic damage and nearly one million deaths. Potent drugs for the treatment of severe SARS-CoV-2 infections are not yet available. To identify host factors that support coronavirus infection, we performed genome-wide functional genetic screens with SARS-CoV-2 and the common cold virus HCoV-229E in non-transgenic human cells. These screens identified PI3K type 3 as a potential drug target against multiple coronaviruses. We discovered that the lysosomal protein TMEM106B is an important host factor for SARS-CoV-2 infection. Furthermore, we show that TMEM106B is required for replication in multiple human cell lines derived from liver and lung and is expressed in relevant cell types in the human airways. Our results identify new coronavirus host factors that may potentially serve as drug targets against SARS-CoV-2 or to quickly combat future zoonotic coronavirus outbreaks.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 28, 2020.
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Identification of TMEM106B as proviral host factor for SARS-CoV-2
Jim Baggen, Leentje Persoons, Sander Jansen, Els Vanstreels, Maarten Jacquemyn, Dirk Jochmans, Johan Neyts, Kai Dallmeier, Piet Maes, Dirk Daelemans
bioRxiv 2020.09.28.316281; doi: https://doi.org/10.1101/2020.09.28.316281
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Identification of TMEM106B as proviral host factor for SARS-CoV-2
Jim Baggen, Leentje Persoons, Sander Jansen, Els Vanstreels, Maarten Jacquemyn, Dirk Jochmans, Johan Neyts, Kai Dallmeier, Piet Maes, Dirk Daelemans
bioRxiv 2020.09.28.316281; doi: https://doi.org/10.1101/2020.09.28.316281

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