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dc.contributor.authorColin, Philippe
dc.contributor.authorZhou, Zhicheng
dc.contributor.authorStaropoli, Isabelle
dc.contributor.authorGarcía-Pérez, Javier 
dc.contributor.authorGasser, Romain
dc.contributor.authorArmani-Tourret, Marie
dc.contributor.authorBenureau, Yann
dc.contributor.authorGonzalez-Fernandez, Nuria 
dc.contributor.authorJin, Jun
dc.contributor.authorConnell, Bridgette J
dc.contributor.authorRaymond, Stéphanie
dc.contributor.authorDelobel, Pierre
dc.contributor.authorIzopet, Jacques
dc.contributor.authorLortat-Jacob, Hugues
dc.contributor.authorAlcamí, José 
dc.contributor.authorArenzana-Seisdedos, Fernando
dc.contributor.authorBrelot, Anne
dc.contributor.authorLagane, Bernard
dc.date.accessioned2019-11-25T12:48:03Z
dc.date.available2019-11-25T12:48:03Z
dc.date.issued2018
dc.identifier.citationPLoS Pathog. 2018 Dec 6;14(12):e1007432.es_ES
dc.identifier.issn1553-7374es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/8696
dc.description.abstractCCR5 plays immune functions and is the coreceptor for R5 HIV-1 strains. It exists in diverse conformations and oligomerization states. We interrogated the significance of the CCR5 structural diversity on HIV-1 infection. We show that envelope glycoproteins (gp120s) from different HIV-1 strains exhibit divergent binding levels to CCR5 on cell lines and primary cells, but not to CD4 or the CD4i monoclonal antibody E51. This owed to differential binding of the gp120s to different CCR5 populations, which exist in varying quantities at the cell surface and are differentially expressed between different cell types. Some, but not all, of these populations are antigenically distinct conformations of the coreceptor. The different binding levels of gp120s also correspond to differences in their capacity to bind CCR5 dimers/oligomers. Mutating the CCR5 dimerization interface changed conformation of the CCR5 homodimers and modulated differentially the binding of distinct gp120s. Env-pseudotyped viruses also use particular CCR5 conformations for entry, which may differ between different viruses and represent a subset of those binding gp120s. In particular, even if gp120s can bind both CCR5 monomers and oligomers, impairment of CCR5 oligomerization improved viral entry, suggesting that HIV-1 prefers monomers for entry. From a functional standpoint, we illustrate that the nature of the CCR5 molecules to which gp120/HIV-1 binds shapes sensitivity to inhibition by CCR5 ligands and cellular tropism. Differences exist in the CCR5 populations between T-cells and macrophages, and this is associated with differential capacity to bind gp120s and to support viral entry. In macrophages, CCR5 structural plasticity is critical for entry of blood-derived R5 isolates, which, in contrast to prototypical M-tropic strains from brain tissues, cannot benefit from enhanced affinity for CD4. Collectively, our results support a role for CCR5 heterogeneity in diversifying the phenotypic properties of HIV-1 isolates and provide new clues for development of CCR5-targeting drugs.es_ES
dc.description.sponsorshipThis work was supported by Agence Nationale de Recherche sur le SIDA et les hépatites virales (ANRS) (http://www.anrs.fr/fr), Institut National de la Santé et de la Recherche Médicale (INSERM) (https://www.inserm.fr), Institut Pasteur (https://www.pasteur.fr), Laboratoire d’Excellence “Integrative Biology of Emerging Infectious Diseases” (Grant ANR-10-LABEX-62-IBEID) (https://research.pasteur.fr/fr/program_project/integrative-biology-of-emerging-infectious-diseases). This work used the platforms of the Grenoble Instruct Centre (ISBG; UMS 3518 CNRS-CEA-UJF-EMBL) (http://www.isbg.fr) with support from FRISBI (ANR-10-INSB-05-02) and GRAL (ANR-10-LABX-49-01) within the Grenoble Partnership for Structural Biology (PSB). JGP was supported by Spanish Ministry of Economy and Competitiveness-ISCIII-FIS No PI16CIII/00034. BJC was supported by a grant from Sidaction (https://www.sidaction.org) and ''la Fondation Pierre Bergé''. ZZ and RG were supported by a grant from ANRS. YB was supported by grants from ANRS and SIDACTION. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.es_ES
dc.language.isoenges_ES
dc.publisherPublic Library of Science (PLOS) es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshHIV Envelope Protein gp120 es_ES
dc.subject.meshHIV Infections es_ES
dc.subject.meshHIV-1 es_ES
dc.subject.meshHumans es_ES
dc.subject.meshPhenotype es_ES
dc.subject.meshProtein Binding es_ES
dc.subject.meshReceptors, CCR5 es_ES
dc.subject.meshVirus Internalization es_ES
dc.titleCCR5 structural plasticity shapes HIV-1 phenotypic propertieses_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID30521629es_ES
dc.format.volume14es_ES
dc.format.number12es_ES
dc.format.pagee1007432es_ES
dc.identifier.doi10.1371/journal.ppat.1007432es_ES
dc.contributor.funderAgence Nationale de Recherches sur le sida et les hépatites virales (Francia) 
dc.contributor.funderInstitut National de la Santé et de la Recherche Médicale (Francia) 
dc.contributor.funderInstituto de Salud Carlos III 
dc.description.peerreviewedes_ES
dc.identifier.e-issn1553-7374es_ES
dc.relation.publisherversionhttps://doi.org/10.1371/journal.ppat.1007432es_ES
dc.identifier.journalPLoS pathogenses_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiología::Área de Patología Molecular::Unidad de Inmunopatología del Sidaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/ANR-10-LABEX-62-IBEIDes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/UMS 3518 CNRS-CEA-UJF-EMBLes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/ANR-10-INSB-05-02es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/ANR-10-LABX-49-01es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI16CIII/00034es_ES
dc.rights.accessRightsopen accesses_ES


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Atribución 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Atribución 4.0 Internacional