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dc.contributor.authorCurriu, Marta
dc.contributor.authorFausther-Bovendo, Hughes
dc.contributor.authorPernas, Maria 
dc.contributor.authorMassanella, Marta
dc.contributor.authorCarrillo, Jorge
dc.contributor.authorCabrera, Cecilia
dc.contributor.authorLopez-Galindez, Luis Cecilio 
dc.contributor.authorClotet, Bonaventura
dc.contributor.authorDebré, Patrice
dc.contributor.authorVieillard, Vincent
dc.contributor.authorBlanco, Julià
dc.identifier.citationPLoS One. 2012;7(2):e30330es_ES
dc.description.abstractBACKGROUND: CD4 T-cell decay is variable among HIV-infected individuals. In exceptional cases, CD4 T-cell counts remain stable despite high plasma viremia. HIV envelope glycoprotein (Env) properties, namely tropism, fusion or the ability to induce the NK ligand NKp44L, or host factors that modulate Env cytopathic mechanisms may be modified in such situation. METHODS: We identified untreated HIV-infected individuals showing non-cytopathic replication (VL>10,000 copies/mL and CD4 T-cell decay<50 cells/µL/year, Viremic Non Progressors, VNP) or rapid progression (CD4 T-cells<350 cells/µL within three years post-infection, RP). We isolated full-length Env clones and analyzed their functions (tropism, fusion activity and capacity to induce NKp44L expression on CD4 cells). Anti-Env humoral responses were also analyzed. RESULTS: Env clones isolated from VNP or RP individuals showed no major phenotypic differences. The percentage of functional clones was similar in both groups. All clones tested were CCR5-tropic and showed comparable expression and fusogenic activity. Moreover, no differences were observed in their capacity to induce NKp44L expression on CD4 T cells from healthy donors through the 3S epitope of gp41. In contrast, anti- Env antibodies showed clear functional differences: plasma from VNPs had significantly higher capacity than RPs to block NKp44L induction by autologous viruses. Consistently, CD4 T-cells isolated from VNPs showed undetectable NKp44L expression and specific antibodies against a variable region flanking the highly conserved 3S epitope were identified in plasma samples from these patients. Conversely, despite continuous antigen stimulation, VNPs were unable to mount a broad neutralizing response against HIV. CONCLUSIONS: Env functions (fusion and induction of NKp44L) were similar in viremic patients with slow or rapid progression to AIDS. However, differences in humoral responses against gp41 epitopes nearby 3S sequence may contribute to the lack of CD4 T cell decay in VNPs by blocking the induction of NKp44L by gp41.es_ES
dc.description.sponsorshipFunding: Spanish AIDS network ‘Red Temática Cooperativa de Investigación en SIDA’, RIS, RD06/0006 (to JB, CLG, MP and MC). “Fundacion para la Investigacion y Prevencion del SIDA en España” FIPSE grant 08/36725 (to CC). Health Department of the Catalan Government (Generalitat de Catalunya) and Instituto de Salud Carlos III (contracts CP04/00271 and CES98/3047 to CC and JB, respectively). Instituto de Salud Carlos III (contract CD09/00150 to JC). Work in CNM is supported by grant SAF 2007-61036 and SAF 2010-17226 and by FIPSE grants 36558/06, 36641/07, 36779/08, 360766/09. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.es_ES
dc.publisherPublic Library of Sciencees_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subject.meshAmino Acid Sequence es_ES
dc.subject.meshCD4 Lymphocyte Count es_ES
dc.subject.meshCD4-Positive T-Lymphocytes es_ES
dc.subject.meshEpitopes es_ES
dc.subject.meshHIV Antibodies es_ES
dc.subject.meshHIV Envelope Protein gp41 es_ES
dc.subject.meshHIV Infections es_ES
dc.subject.meshHIV-1 es_ES
dc.subject.meshHumans es_ES
dc.subject.meshImmunity, Humoral es_ES
dc.subject.meshMolecular Sequence Data es_ES
dc.subject.meshNatural Cytotoxicity Triggering Receptor 2 es_ES
dc.subject.meshTime Factors es_ES
dc.subject.meshViral Tropism es_ES
dc.subject.meshViremia es_ES
dc.subject.meshVirus Internalization es_ES
dc.subject.meshAntibody Specificity es_ES
dc.titleViremic HIV infected individuals with high CD4 T cells and functional envelope proteins show anti-gp41 antibodies with unique specificity and functiones_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderRed Temática Cooperativa de Investigación en SIDA (España)es_ES
dc.contributor.funderFundacion para la Investigacion y Prevencion del SIDA en Españaes_ES
dc.contributor.funderInstituto de Salud Carlos III - ISCIIIes_ES
dc.contributor.funderGeneralitat de Catalunyaes_ES
dc.identifier.journalPloS onees_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES

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