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dc.contributor.authorSalgado, María
dc.contributor.authorMartinez-Picado, Javier
dc.contributor.authorGálvez, Cristina
dc.contributor.authorRivaya, Belén
dc.contributor.authorUrrea, Víctor
dc.contributor.authorRodriguez Mora, Sara 
dc.contributor.authorMateos, Elena 
dc.contributor.authorAlcamí, José 
dc.contributor.authorCoiras, Mayte
dc.identifier.citationBiochem Pharmacol. 2020 Apr;174:113625.es_ES
dc.description.abstractHIV-1 infection remains incurable despite the efficient combined antiretroviral therapy (cART) due to the formation of long-lived viral reservoirs that are mostly settled in CD4+T cells and maintained by homeostatic proliferation. The use of cytostatic drugs such as tyrosine kinase inhibitors (TKIs) as adjuvants to cART could be helpful to avoid the reservoir establishment and replenishment. We determined previously that TKI dasatinib, which is successfully used for treating chronic myeloid leukemia (CML), shows antiviral effect against HIV-1 infection of CD4+ T cells in vitro. HIV-infected subjects that developed CML may safely combine long-term treatment with TKIs and cART but there is no information about the effect of dasatinib on HIV-1 reservoir in vivo. Therefore, we analyzed the ability of dasatinib to protect NSG mice engrafted with human CD34+ hematopoietic stem cells from HIV-1 infection. Mice were randomly assigned to two groups that received dasatinib or placebo daily by oral gavage. After five days, all mice were infected intraperitoneally with HIV-1 and followed up for 21 days in the absence of cART. Daily administration of dasatinib decreased viral and proviral load in all treated mice, showing in 40% of these mice undetectable viral RNA or DNA in blood. Proviral HIV-1 DNA in gut-associated lymphoid tissue (GALT) was also reduced in all dasatinib-treated mice and under the limit of detection in one of these mice. Finally, treatment with dasatinib modified the distribution of CD4+ and CD8+ T-cell subpopulations, delaying their differentiation into memory T-cell subsets that are a major component of the viral reservoir. In conclusion, dasatinib afforded protection of NSG mice from HIV-1 intraperitoneal infection in the absence of cART.es_ES
dc.description.sponsorshipFunding for this research was provided by: Ministerio de Economía y Competitividad (SAF2013-44677-R, SAF2016-78480-R) Ministerio de Ciencia, Innovación y Universidades (FIS PI16CIII/00034-ISCIII-FEDER) European Regional Development Fund Bristol-Myers Squibb (BMS AI471-041) Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS 2014-2) Spanish Ministry of Education, Culture and Sport (FPU15/03698).es_ES
dc.publisherElsevier es_ES
dc.titleDasatinib protects humanized mice from acute HIV-1 infectiones_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.contributor.funderMinisterio de Economía y Competitividad (España)
dc.contributor.funderMinisterio de Ciencia, Innovación y Universidades (España)
dc.contributor.funderEuropean Regional Development Fund 
dc.contributor.funderBristol-Myers Squibb
dc.contributor.funderAgence Nationale de Recherches sur le sida et les hépatites virales (Francia)
dc.contributor.funderMinisterio de Educación, Cultura y Deporte (España)
dc.identifier.journalBiochemical pharmacologyes_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/FIS PI16CIII/00034-ISCIII-FEDERes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/BMS AI471-041es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/ANRS 2014-2es_ES

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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
This item is licensed under a: Attribution-NonCommercial-NoDerivatives 4.0 Internacional