Title |
Autophagy‐linked plasma and lysosomal membrane protein PLAC8 is a key host factor for SARS‐CoV‐2 entry into human cells
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Published in |
EMBO Journal, October 2022
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DOI | 10.15252/embj.2022110727 |
Pubmed ID | |
Authors |
Alejandro P Ugalde, Gabriel Bretones, David Rodríguez, Víctor Quesada, Francisco Llorente, Raúl Fernández‐Delgado, Miguel Ángel Jiménez‐Clavero, Jesús Vázquez, Enrique Calvo, Isaac Tamargo‐Gómez, Guillermo Mariño, David Roiz‐Valle, Daniel Maeso, Miguel Araujo‐Voces, Yaiza Español, Carles Barceló, José MP Freije, Alejandro López‐Soto, Carlos López‐Otín |
Abstract |
Better understanding interactions between SARS-CoV-2 and host cells should help to identify host factors that may be targetable to combat infection and COVID-19 pathology. To this end, we have conducted a genome-wide CRISPR/Cas9-based loss-of-function screen in human lung cancer cells infected with SARS-CoV-2-pseudotyped lentiviruses. Our results recapitulate many findings from previous screens that used full SARS-CoV-2 viruses, but also unveil two novel critical host factors: the lysosomal efflux transporter SPNS1 and the plasma and lysosomal membrane protein PLAC8. Functional experiments with full SARS-CoV-2 viruses confirm that loss-of-function of these genes impairs viral entry. We find that PLAC8 is a key limiting host factor, whose overexpression boosts viral infection in eight different human lung cancer cell lines. Using single-cell RNA-Seq data analyses, we demonstrate that PLAC8 is highly expressed in ciliated and secretory cells of the respiratory tract as well as in gut enterocytes, cell types that are highly susceptible to SARS-CoV-2 infection. Proteomics and cell biology studies suggest that PLAC8 and SPNS1 regulate the autophagolysosomal compartment and affect the intracellular fate of endocytosed virions. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Spain | 16 | 33% |
Germany | 2 | 4% |
India | 1 | 2% |
Hungary | 1 | 2% |
United States | 1 | 2% |
Morocco | 1 | 2% |
Portugal | 1 | 2% |
United Kingdom | 1 | 2% |
Mexico | 1 | 2% |
Other | 0 | 0% |
Unknown | 23 | 48% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 42 | 88% |
Scientists | 4 | 8% |
Practitioners (doctors, other healthcare professionals) | 2 | 4% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 27 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 5 | 19% |
Researcher | 3 | 11% |
Other | 2 | 7% |
Student > Doctoral Student | 2 | 7% |
Student > Master | 2 | 7% |
Other | 3 | 11% |
Unknown | 10 | 37% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 6 | 22% |
Medicine and Dentistry | 4 | 15% |
Agricultural and Biological Sciences | 2 | 7% |
Unspecified | 1 | 4% |
Mathematics | 1 | 4% |
Other | 3 | 11% |
Unknown | 10 | 37% |