2026-06-14T02:28:50Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/103002024-11-28T17:56:53Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19609col_20.500.12105_16961
Repisalud author Salgado, María author Martinez-Picado, Javier author Gálvez, Cristina author Rivaya, Belén author Urrea, Víctor author Rodriguez Mora, Sara author Mateos, Elena author Alcamí, José author Coiras, Mayte funder Ministerio de Economía y Competitividad (España) funder Ministerio de Ciencia, Innovación y Universidades (España) funder Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) funder Bristol-Myers Squibb funder Agence Nationale de Recherches sur le sida et les hépatites virales (Francia) funder Ministerio de Educación, Cultura y Deporte (España) 2020-06-09T10:20:32Z 2020-06-09T10:20:32Z 2020-04 Biochem Pharmacol. 2020 Apr;174:113625. 10.1016/j.bcp.2019.113625 1873-2968 Biochemical pharmacology 31476293 http://hdl.handle.net/20.500.12105/10300 HIV-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. eng Dasatinib protects humanized mice from acute HIV-1 infection research article TElDRU5DSUEgREUgRElTVFJJQlVDScOTTiBOTyBFWENMVVNJVkEKCkFjZXB0YW5kbyBlc3RhIGxpY2VuY2lhLCBVc3RlZCAoZWwgYXV0b3IvZXMgbyBlbCBwcm9waWV0YXJpby9zIGRlIGxvcyBkZXJlY2hvcyBkZSAKYXV0b3IpIGNvbmNlZGUgYSBSRVBJU0FMVUQgZWwgZGVyZWNobyBubyBleGNsdXNpdm8gZGUgcmVwcm9kdWNpciwgY29udmVydGlyLCB5L28gCmRpc3RyaWJ1aXIgc3UgZG9jdW1lbnRvIChpbmNsdXllbmRvIHN1IHJlc3VtZW4pIGEgbml2ZWwgbXVuZGlhbCBlbiBmb3JtYXRvIGRpZ2l0YWwsIAppbmNsdXllbmRvLCBhdWRpbyB5IHbDrWRlbywgYSB0cmF2w6lzIGRlIHN1IHJlcG9zaXRvcmlvIGluc3RpdHVjaW9uYWwuCgpVc3RlZCBhY2VwdGEgcXVlIFJFUElTQUxVRCBwdWVkZSwgc2luIGFsdGVyYXIgc3UgY29udGVuaWRvLCBjb252ZXJ0aXIgc3UgZG9jdW1lbnRvIAphIGN1YWxxdWllciBvdHJvIGZvcm1hdG8gZGlnaXRhbCBkZSBkYXRvcywgYXVkaW8geSB2aWRlbywgY29uIGVsIHByb3DDs3NpdG8gZGUgcXVlIApwdWVkYSBzZXIgYWxvamFkbyBlbiBlbCByZXBvc2l0b3Jpby4gCgpVc3RlZCBlc3TDoSBkZSBhY3VlcmRvIGNvbiBxdWUgUkVQSVNBTFVEIHB1ZWRhIGNvbnNlcnZhciBtw6FzIGRlIHVuYSBjb3BpYSBkZSBlc3RlIApkb2N1bWVudG8gcGFyYSBhc2VndXJhciBzdSBzZWd1cmlkYWQsIHByZXNlcnZhY2nDs24geSBhY2Nlc28uCgpVc3RlZCBkZWNsYXJhIHF1ZSBlbCBkb2N1bWVudG8gZXMgdW4gdHJhYmFqbyBvcmlnaW5hbCwgeSBxdWUgdGllbmUgZWwgZGVyZWNobyBkZSAKb3RvcmdhciBsb3MgZGVyZWNob3MgY29udGVuaWRvcyBlbiBlc3RhIGxpY2VuY2lhLiBUYW1iacOpbiBkZWNsYXJhIHF1ZSBzdSBwZXRpY2nDs24gCm5vIGluZnJpbmdlIGxvcyBkZXJlY2hvcyBkZSBhdXRvciBkZSBuYWRpZS4gCgpTaSBlbCBkb2N1bWVudG8gY29udGllbmUgbWF0ZXJpYWxlcyBwYXJhIGxvcyBxdWUgbm8gc2UgdGllbmVuIGxvcyBkZXJlY2hvcyBkZSBhdXRvciwgClVzdGVkIGRlY2xhcmEgcXVlIGhhIG9idGVuaWRvIGVsIHBlcm1pc28gc2luIHJlc3RyaWNjacOzbiBkZWwgcHJvcGlldGFyaW8gZGUgbG9zIApkZXJlY2hvcyB5IHF1ZSBlbiBkaWNobyBtYXRlcmlhbCwgZXN0w6EgY2xhcmFtZW50ZSBpZGVudGlmaWNhZGEgeSByZWNvbm9jaWRhIHN1IAphdXRvcsOtYSBkZW50cm8gZWwgdGV4dG8gbyBkZWwgY29udGVuaWRvIGRlIGRpY2hvIGRvY3VtZW50by4gCgpTaSBlbCBlbnbDrW8gc2UgYmFzYSBlbiB1biB0cmFiYWpvIHF1ZSBoYSBzaWRvIHBhdHJvY2luYWRvIG8gYXBveWFkbyBwb3IgdW5hIGFnZW5jaWEgCnUgb3JnYW5pemFjacOzbiBkaXN0aW50YSBhIFJFUElTQUxVRCwgdXN0ZWQgYWNlcHRhIHF1ZSBoYSBjdW1wbGlkbyBjb24gZWwgZGVyZWNobyBkZSAKcmV2aXNpw7NuIHkgb3RyYXMgb2JsaWdhY2lvbmVzIHJlcXVlcmlkYXMgcG9yIGNvbnRyYXRvIG8gYWN1ZXJkby4gCgpSRVBJU0FMVUQgaWRlbnRpZmljYXLDoSBjbGFyYW1lbnRlIHN1KHMpIG5vbWJyZShzKSBjb21vIGF1dG9yKHMpIG8gcHJvcGlldGFyaW8ocykgCmRlbCBkb2N1bWVudG8sIHkgbm8gaGFyw6EgbmluZ3VuYSBhbHRlcmFjacOzbiwgZXhjZXB0byBzZWfDum4gbG8gcGVybWl0aWRvIHBvciBlc3RhIApsaWNlbmNpYS4gCg== URL https://repisalud.isciii.es/bitstreams/90045e14-0f3c-4fef-b661-386ad9fb0a0b/download File MD5 e525091a13e1bb4a1258c432c731b4d2 310616 application/pdf DasatinibProtectsHumanizedMice_2020.pdf URL https://repisalud.isciii.es/bitstreams/e185ab7c-5d20-4526-8169-458f2855ab5f/download File MD5 e67fd5f0451238f49fa368ecb13b2ab5 40169 text/plain DasatinibProtectsHumanizedMice_2020.pdf.txt