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dc.contributor.authorLopez-Huertas, Maria Rosa 
dc.contributor.authorMateos, Elena 
dc.contributor.authorDíaz-Gil, Gema
dc.contributor.authorGómez-Esquer, Francisco
dc.contributor.authorSanchez-Del Cojo, Maria 
dc.contributor.authorAlcamí, José 
dc.contributor.authorCoiras, Mayte 
dc.date.accessioned2019-06-03T12:55:59Z
dc.date.available2019-06-03T12:55:59Z
dc.date.issued2011-08
dc.identifier.citationJ Biol Chem. 2011;286(31):27363-77.es_ES
dc.identifier.issn0021-9258es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/7711
dc.description.abstractIntegration of HIV-1 genome in CD4(+) T cells produces latent reservoirs with long half-life that impedes the eradication of the infection. Control of viral replication is essential to reduce the size of latent reservoirs, mainly during primary infection when HIV-1 infects CD4(+) T cells massively. The addition of immunosuppressive agents to highly active antiretroviral therapy during primary infection would suppress HIV-1 replication by limiting T cell activation, but these agents show potential risk for causing lymphoproliferative disorders. Selective inhibition of PKC, crucial for T cell function, would limit T cell activation and HIV-1 replication without causing general immunosuppression due to PKC being mostly expressed in T cells. Accordingly, the effect of rottlerin, a dose-dependent PKC inhibitor, on HIV-1 replication was analyzed in T cells. Rottlerin was able to reduce HIV-1 replication more than 20-fold in MT-2 (IC(50) = 5.2 μM) and Jurkat (IC(50) = 2.2 μM) cells and more than 4-fold in peripheral blood lymphocytes (IC(50) = 4.4 μM). Selective inhibition of PKC, but not PKCδ or -ζ, was observed at <6.0 μM, decreasing the phosphorylation at residue Thr(538) on the kinase catalytic domain activation loop and avoiding PKC translocation to the lipid rafts. Consequently, the main effector at the end of PKC pathway, NF-κB, was repressed. Rottlerin also caused a significant inhibition of HIV-1 integration. Recently, several specific PKC inhibitors have been designed for the treatment of autoimmune diseases. Using these inhibitors in combination with highly active antiretroviral therapy during primary infection could be helpful to avoid massive viral infection and replication from infected CD4(+) T cells, reducing the reservoir size at early stages of the infection.es_ES
dc.description.sponsorshipThis work was supported by Instituto de Salud Carlos III, Spanish Ministry of Health (FIS PI080752); AIDS Network ISCIII-RETIC (RD06/0006); VIRHORST Network from Comunidad de Madrid (Spain), Network of Excellence EUROPRISE; FIPSE (36584/06, 36633/07, and 360924/10).es_ES
dc.language.isoenges_ES
dc.publisherAmerican Society for Biochemistry and Molecular Biologyes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleProtein Kinase Cθ Is a Specific Target for Inhibition of the HIV Type 1 Replication in CD4+T Lymphocyteses_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID21669868es_ES
dc.format.volume286es_ES
dc.format.number31es_ES
dc.format.page27377es_ES
dc.identifier.doi10.1074/jbc.M110.210443es_ES
dc.contributor.funderComunidad de Madrid
dc.contributor.funderInstituto de Salud Carlos III - ISCIII
dc.contributor.funderMinisterio de Sanidad y Consumo (España)
dc.contributor.funderFundación para la Innovación y la Prospectiva en Salud en España (FIPSE)
dc.contributor.funderEuropean Network of Excellence EUROPRISE
dc.description.peerreviewedes_ES
dc.identifier.e-issn1083-351Xes_ES
dc.relation.publisherversionhttps://www.doi.org/10.1074/jbc.M110.210443.es_ES
dc.identifier.journalJournal of Biological Chemistryes_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionCNIOes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/FIS PI080752es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD06/0006es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/36584/06es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/36633/07es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/360924/10es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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