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dc.contributor.authorRamirez de Arellano, Eva 
dc.contributor.authorDíez-Fuertes, Francisco 
dc.contributor.authorAguilar, Francisco 
dc.contributor.authorde la Torre-Tarazona, Humberto Erick 
dc.contributor.authorSanchez-Lara, Susana 
dc.contributor.authorLao, Yolanda 
dc.contributor.authorVicario, José Luis
dc.contributor.authorGarcía, Felipe
dc.contributor.authorGonzález-Garcia, Juan
dc.contributor.authorPulido, Federico
dc.contributor.authorGutierrez-Rodero, Félix
dc.contributor.authorMoreno, Santiago
dc.contributor.authorIribarren, Jose Antonio
dc.contributor.authorViciana, Pompeyo
dc.contributor.authorVilches, Carlos
dc.contributor.authorRamos, Manuel 
dc.contributor.authorCapa, Laura 
dc.contributor.authorAlcamí, José 
dc.contributor.authorVal, Margarita del 
dc.date.accessioned2019-11-25T12:59:07Z
dc.date.available2019-11-25T12:59:07Z
dc.date.issued2019
dc.identifier.citationPLoS One. 2019 Aug 8;14(8):e0220459.es_ES
dc.identifier.issn1932-6203es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/8707
dc.description.abstractCertain host genetic variants, especially in the human leucocyte antigen (HLA) region, are associated with different progression of HIV-1-induced diseases and AIDS. Long term non progressors (LTNP) represent only the 2% of infected patients but are especially relevant because of their efficient HIV control. In this work we present a global analysis of genetic data in the large national multicenter cohort of Spanish LTNP, which is compared with seronegative individuals and HIV-positive patients. We have analyzed whether several single-nucleotide polymorphisms (SNPs) including in key genes and certain HLA-A and B alleles could be associated with a specific HIV phenotype. A total of 846 individuals, 398 HIV-1-positive patients (213 typical progressors, 55 AIDS patients, and 130 LTNPs) and 448 HIV-negative controls, were genotyped for 15 polymorphisms and HLA-A and B alleles. Significant differences in the allele frequencies among the studied populations identified 16 LTNP-associated genetic factors, 5 of which were defined for the first time as related to LTNP phenotype: the protective effect of HLA-B39, and the detrimental impact of HLA-B18, -A24, -B08 and -A29. The remaining eleven polymorphisms confirmed previous publications, including the protective alleles HLA-B57, rs2395029 (HCP5), HLA bw4 homozygosity, HLA-B52, HLA-B27, CCR2 V64I, rs9264942 (HLA-C) and HLA-A03; and the risk allele HLA bw6 homozygosity. Notably, individual Spanish HIV-negative individuals had an average of 0.12 protective HLA alleles and SNPs, compared with an average of 1.43 protective alleles per LTNP patient, strongly suggesting positive selection of LTNP. Finally, stratification of LTNP according to viral load showed a proportional relationship between the frequency of protective alleles with control of viral load. Interestingly, no differences in the frequency of protection/risk polymorphisms were found between elite controllers and LTNPs maintaining viral loads <2.000 copies/mL throughout the follow-up.es_ES
dc.description.sponsorshipThis work was supported by Instituto de Salud Carlos III from the Spanish Ministry of Health, through Red Temática de Investigación Cooperativa en SIDA (RIS) [G03/173(2), PI050528 and RD06/0006/0033 to MDV, RD06/0006/0035 and RD12/0017/0037 to the HIV BioBank, and C03/173 and RD12/0017/0018 to CoRIS], cofinanced by ISCIII-Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER), and also financed by Plan Nacional I+D+I from the Spanish Ministry of Science and Technology [SAF2007-60934, SAF2010-18917 and SAF2013- 48754-C2-1-R to MDV], by Instituto de Salud Carlos III [Intrasalud PI12/0056 to JA] and by Fundación para la Investigación y Prevención del SIDA en España (FIPSE) [to HIV Biobank]. Institutional grants from the Fundación Ramón Areces and Banco de Santander to the CBMSO are also acknowledged. FDF is supported by the Spanish Government’s “Sara Borrell” postdoctoral program CD12/00515. The funders had no role in study design, decision to publish, analysis and 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.titleNovel association of five HLA alleles with HIV-1 progression in Spanish long-term non progressor patientses_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID31393887es_ES
dc.format.volume14es_ES
dc.format.number8es_ES
dc.format.pagee0220459es_ES
dc.identifier.doi10.1371/journal.pone.0220459es_ES
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderRed de Investigación Cooperativa en Investigación en Sida (España) 
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 
dc.contributor.funderMinisterio de Ciencia y Tecnología (España) 
dc.contributor.funderFundación para la Investigación y la Prevención del Sida en España 
dc.contributor.funderFundación Ramón Areces 
dc.contributor.funderBanco Santander 
dc.description.peerreviewedes_ES
dc.identifier.e-issn1932-6203es_ES
dc.relation.publisherversionhttps://doi.org/10.1371/journal.pone.0220459es_ES
dc.identifier.journalPloS onees_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI050528es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD06/0006/0033es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD06/0006/0035es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD12/0017/0037es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD12/0017/0018es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2007-60934es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2010-18917es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2013- 48754-C2-1-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI12/0056es_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