dc.contributor.author | Ugalde, Alejandro P | |
dc.contributor.author | Bretones, Gabriel | |
dc.contributor.author | Rodríguez, David | |
dc.contributor.author | Quesada, Víctor | |
dc.contributor.author | Llorente, Francisco | |
dc.contributor.author | Fernández-Delgado, Raúl | |
dc.contributor.author | Jiménez-Clavero, Miguel Ángel | |
dc.contributor.author | Vazquez, Jesus | |
dc.contributor.author | Calvo, Enrique | |
dc.contributor.author | Tamargo-Gómez, Isaac | |
dc.contributor.author | Mariño, Guillermo | |
dc.contributor.author | Roiz-Valle, David | |
dc.contributor.author | Maeso, Daniel | |
dc.contributor.author | Araujo-Voces, Miguel | |
dc.contributor.author | Español, Yaiza | |
dc.contributor.author | Barceló, Carles | |
dc.contributor.author | Freije, José Mp | |
dc.contributor.author | López-Soto, Alejandro | |
dc.contributor.author | López-Otín, Carlos | |
dc.date.accessioned | 2022-12-09T10:49:10Z | |
dc.date.available | 2022-12-09T10:49:10Z | |
dc.date.issued | 2022-11-02 | |
dc.identifier.citation | EMBO J. 2022 Nov 2;41(21):e110727 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/15263 | |
dc.description.abstract | Better understanding on 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. | es_ES |
dc.description.sponsorship | We thank Marisa Arias and Luis Enjuanes for their support and suggestions.
We thank Xose S. Puente, Xurde M. Caravia, Alicia R. Folgueras, Pedro M.
Quir
os, and Manuel Illescas for their helpful advice and comments on the
manuscript. We thank Mar ıa Dolores Chiara for technical support. We thank
Marta Alonso Guerv
os, Ana Salas Bustamante, Jos e Luis Mart ınez Fern andez,
Daniel Serna Fuente, and Marcos Garc ıa Ocana from the microscopy, cytome- ~
try, sequencing, and cell-culture core facilities of the University of Oviedo for
their technical support. We thank Ignacio Varela and Juana Mar ıa Garc ıa
Pedrero for sharing reagents. This work was supported by Instituto de Salud
Carlos III(COV20/00652, MS19/00100, PI20/01267, COV20/00571 and PT17/
0019/0003), Ministerio de Ciencia e Innovacion (Spain) (PDI 2020-118394RB100, SAF2017-87655-R, PID2021-127534OB-100, and PGC2018-097019-B-I00),
“laCaixa” Banking Foundation (HR17-00247) and Consejer ıa de Ciencia, Innovacion y Universidad del Gobierno del Principado de Asturias (AYUD/ 2021/
57167). D.R.V and D.M are supported by PhD fellowships from Ministerio de
Ciencia e Innovacion(Spain). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | EMBO Press | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.mesh | COVID-19 | es_ES |
dc.subject.mesh | Lung Neoplasms | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | SARS-CoV-2 | es_ES |
dc.subject.mesh | Angiotensin-Converting Enzyme 2 | es_ES |
dc.subject.mesh | Lysosome-Associated Membrane Glycoproteins | es_ES |
dc.subject.mesh | Autophagy | es_ES |
dc.subject.mesh | Proteins | es_ES |
dc.title | Autophagy-linked plasma and lysosomal membrane protein PLAC8 is a key host factor for SARS-CoV-2 entry into human cells. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 36124427 | es_ES |
dc.format.volume | 41 | es_ES |
dc.format.number | 21 | es_ES |
dc.format.page | e110727 | es_ES |
dc.identifier.doi | 10.15252/embj.2022110727 | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | es_ES |
dc.contributor.funder | Fundación La Caixa | es_ES |
dc.contributor.funder | Gobierno del Principado de Asturias (España) | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1460-2075 | es_ES |
dc.relation.publisherversion | 10.15252/embj.2022110727 | es_ES |
dc.identifier.journal | The EMBO journal | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Proteómica cardiovascular | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/COV20/00652 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/MS19/00100 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PI20/01267 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/COV20/00571 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PT17/0019/0003 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/DI/2020-118394RB100 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/SAF2017-87655-R | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2021-127534OB-100 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PGC2018-097019-B-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/HR17-00247 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/AYUD/2021/57167 | es_ES |