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dc.contributor.author | Colomer-Lluch, Marta | |
dc.contributor.author | Kilpelainen, Athina | |
dc.contributor.author | Pernas, Maria | |
dc.contributor.author | Peña, Ruth | |
dc.contributor.author | Ouchi, Dan | |
dc.contributor.author | Jiménez-Moyano, Esther | |
dc.contributor.author | Dalmau, Judith | |
dc.contributor.author | Casado, Concepcion | |
dc.contributor.author | Lopez-Galindez, Luis Cecilio | |
dc.contributor.author | Clotet, Bonaventura | |
dc.contributor.author | Martinez-Picado, Javier | |
dc.contributor.author | Prado, Julia G | |
dc.date.accessioned | 2022-05-17T10:15:03Z | |
dc.date.available | 2022-05-17T10:15:03Z | |
dc.date.issued | 2022-01-12 | |
dc.identifier.citation | J Virol. 2022 Jan 12;96(1):e0149921. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/14401 | |
dc.description.abstract | Human immunodeficiency virus type 1 (HIV-1) viremic nonprogressors (VNPs) represent a very rare HIV-1 extreme phenotype. VNPs are characterized by persistent high plasma viremia and maintenance of CD41 T-cell counts in the absence of treatment. However, the causes of nonpathogenic HIV-1 infection in VNPs remain elusive. Here, we identified for the first time two VNPs who experienced the loss of CD41 homeostasis (LoH) after more than 13 years. We characterized in deep detail viral and host factors associated with the LoH and compared with standard VNPs and healthy controls. The viral factors determined included HIV-1 coreceptor usage and replicative capacity. Changes in CD41 and CD81 T-cell activation, maturational phenotype, and expression of CCR5 and CXCR6 in CD41 T-cells were also evaluated as host-related factors. Consistently, we determined a switch in HIV-1 coreceptor use to CXCR4 concomitant with an increase in replicative capacity at the LoH for the two VNPs. Moreover, we delineated an increase in the frequency of HLA-DR1CD381 CD41 and CD81 T cells and traced the augment of naive T-cells upon polyclonal activation with LoH. Remarkably, very low and stable levels of CCR5 and CXCR6 expression in CD41 T-cells were measured over time. Overall, our results demonstrated HIV-1 evolution toward highly pathogenic CXCR4 strains in the context of very limited and stable expression of CCR5 and CXCR6 in CD41 T cells as potential drivers of LoH in VNPs. These data bring novel insights into the correlates of nonpathogenic HIV1 infection. Importance: The mechanism behind nonpathogenic human immunodeficiency virus type 1 (HIV-1) infection remains poorly understood, mainly because of the very low frequency of viremic nonprogressors (VNPs). Here, we report two cases of VNPs who experienced the loss of CD41 T-cell homeostasis (LoH) after more than 13 years of HIV-1 infection. The deep characterization of viral and host factors supports the contribution of viral and host factors to the LoH in VNPs. Thus, HIV-1 evolution toward highly replicative CXCR4 strains together with changes in T-cell activation and maturational phenotypes were found. Moreover, we measured very low and stable levels of CCR5 and CXCR6 in CD41 T-cells over time. These findings support viral evolution toward X4 strains limited by coreceptor expression to control HIV-1 pathogenesis and demonstrate the potential of host-dependent factors, yet to be fully elucidated in VNPs, to control HIV-1 pathogenesis. | es_ES |
dc.description.sponsorship | This research was supported by a Gilead Fellowship (grant GLD15/0298) and La Caixa Foundation (grant LCF/PR/PR16/11110026). M.C.-L. is a Beatriu de Pinós postdoctoral fellow (grant BP 00075) supported by the Government of Catalonia’s Secretariat for Universities and Research of the Ministry of Economy and Knowledge. J.G.P. was supported by the ISCIII (grant CP15/00014). E.J.-M. was funded by Redes Temáticas de Investigación en SIDA (ISCIII RETIC RD16/0025/0041); Acción Estratégica en Salud; Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica 2008–2011; and Instituto de Salud Carlos III. E.J.-M. was cofunded by European Regional Development Fund/European Social Fund (FEDER) “Investing in your future.” J.M.-P. is supported by the Spanish Ministry of Science and Innovation (grant PID2019-109870RB-I00). J.G.P. and M.C.-L. designed the study, supervised experiments and data. J.G.P., M.C.-L., and A.K. contributed to data interpretation. M.C.-L., R.P., E.J.-M., M.P., and C.C. performed experiments, analyzed, and interpreted the data. J.D. carried out the clinical follow-up and patient identification. M.C.-L., D.O., M.P., and C.C. performed data analysis. M.C.-L., A.K., M.P., C.L.-G., B.C., J.M.-P., and J.G.P. performed manuscript writing, critical revision, and discussion. We declare no conflict of interest. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | American Society for Microbiology (ASM) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | HIV-1 | es_ES |
dc.subject | Viremic nonprogressors | es_ES |
dc.subject | Loss of CD4 homeostasis | es_ES |
dc.subject | Replication | es_ES |
dc.subject | Coreceptor usage | es_ES |
dc.subject | T-cell activation | es_ES |
dc.subject | T-cell maturational phenotypes | es_ES |
dc.subject | CCR5 | es_ES |
dc.subject | CXCR6 | es_ES |
dc.subject | Human immunodeficiency virus | es_ES |
dc.title | Viral and Cellular factors leading to the Loss of CD4 Homeostasis in HIV-1 Viremic Nonprogressors | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 34668779 | es_ES |
dc.format.volume | 96 | es_ES |
dc.format.number | 1 | es_ES |
dc.format.page | e0149921 | es_ES |
dc.identifier.doi | 10.1128/JVI.01499-21 | es_ES |
dc.contributor.funder | Gilead Sciences (Spain) | es_ES |
dc.contributor.funder | Fundación La Caixa | es_ES |
dc.contributor.funder | Government of Catalonia (España) | es_ES |
dc.contributor.funder | Ministerio de Economía e Innovación (España) | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.contributor.funder | Red de Investigación Cooperativa en Investigación en Sida (España) | es_ES |
dc.contributor.funder | Plan Nacional de I+D+i (España) | es_ES |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1098-5514 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1128/JVI.01499-21 | es_ES |
dc.identifier.journal | Journal of Virology | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Microbiología | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2019-109870RB-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/MINECO//RD16%2F0025%2F0041/ES/RED ESPAÑOLA DE INVESTIGACIÓN EN SIDA (RIS)/ | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/CP15/00014 | es_ES |