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The Phospholipid Scramblases 1 and 4 Are Cellular Receptors for the Secretory Leukocyte Protease Inhibitor and Interact with CD4 at the Plasma Membrane

dc.contributor.authorPy, Bénédicte
dc.contributor.authorBasmaciogullari, Stéphane
dc.contributor.authorBouchet, Jérôme
dc.contributor.authorZarka, Marion
dc.contributor.authorMoura, Ivan
dc.contributor.authorBenhamou, Marc
dc.contributor.authorMonteiro, Renato
dc.contributor.authorHocini, Hakim
dc.contributor.authorMadrid González, Ricardo
dc.contributor.authorBenichou, Serge
dc.date.accessioned2024-02-02T13:16:08Z
dc.date.available2024-02-02T13:16:08Z
dc.date.issued2009
dc.description.abstractSecretory leukocyte protease inhibitor (SLPI) is secreted by epithelial cells in all the mucosal fluids such as saliva, cervical mucus, as well in the seminal liquid. At the physiological concentrations found in saliva, SLPI has a specific antiviral activity against HIV-1 that is related to the perturbation of the virus entry process at a stage posterior to the interaction of the viral surface glycoprotein with the CD4 receptor. Here, we confirm that recombinant SLPI is able to inhibit HIV-1 infection of primary T lymphocytes, and show that SLPI can also inhibit the transfer of HIV-1 virions from primary monocyte-derived dendritic cells to autologous T lymphocytes. At the molecular level, we show that SLPI is a ligand for the phospholipid scramblase 1 (PLSCR1) and PLSCR4, membrane proteins that are involved in the regulation of the movements of phospholipids between the inner and outer leaflets of the plasma membrane. Interestingly, we reveal that PLSCR1 and PLSCR4 also interact directly with the CD4 receptor at the cell surface of T lymphocytes. We find that the same region of the cytoplasmic domain of PLSCR1 is involved in the binding to CD4 and SLPI. Since SLPI was able to disrupt the association between PLSCR1 and CD4, our data suggest that SLPI inhibits HIV-1 infection by modulating the interaction of the CD4 receptor with PLSCRs. These interactions may constitute new targets for antiviral intervention
dc.description.departmentDepto. de Genética, Fisiología y Microbiología
dc.description.facultyFac. de Ciencias Biológicas
dc.description.refereedTRUE
dc.description.statuspub
dc.identifier.citationPy B, Basmaciogullari S, Bouchet J, Zarka M, Moura IC, Benhamou M, et al. (2009) The Phospholipid Scramblases 1 and 4 Are Cellular Receptors for the Secretory Leukocyte Protease Inhibitor and Interact with CD4 at the Plasma Membrane. PLoS ONE 4(3): e5006. https://doi.org/10.1371/journal.pone.0005006
dc.identifier.doi10.1371/journal.pone.0005006
dc.identifier.issn1932-6203
dc.identifier.officialurlhttps://doi.org/10.1371/journal.pone.0005006
dc.identifier.urihttps://hdl.handle.net/20.500.14352/98313
dc.journal.titlePLos One
dc.language.isoeng
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.cdu577.112
dc.subject.ucmBioquímica (Biología)
dc.subject.unesco2403 Bioquímica
dc.titleThe Phospholipid Scramblases 1 and 4 Are Cellular Receptors for the Secretory Leukocyte Protease Inhibitor and Interact with CD4 at the Plasma Membrane
dc.typejournal article
dc.type.hasVersionVoR
dspace.entity.typePublication
relation.isAuthorOfPublication38610649-8d87-431b-8b40-b51ae401b990
relation.isAuthorOfPublication.latestForDiscovery38610649-8d87-431b-8b40-b51ae401b990

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