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The authors are grateful to all the patients and donors who participated in the study and thank the Retrovirology and Viral Immunopathology Laboratory of the Institut d`Investigacions Biomediques August Pi I Sunyer (IDIBAPS). This work was partially supported by HIVACAT (HIV Vaccine Research and Development Programme in Catalonia), Fundacion para la Investigacion y la Prevencion del Sida en Espana (FIPSE 09), Fondo Europeo para el Desarrollo Regional (FEDER), Fondo de Investigacion Sanitaria (FIS; PI070291, PI12/00969), Red de Investigacion en Sida (RIS), and Instituto de Salud Carlos III (ISCIII-RETIC RD06/0006/0000). M. Plana and M. Arnedo are researchers from the Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS) and were supported by the Spanish Health Department of the Instituto de Salud Carlos III (ISCIII) and the Health Department of the Catalan Government (Generalitat de Catalunya). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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MicroRNA Profile in CD8+T-Lymphocytes from HIV-Infected Individuals: Relationship with Antiviral Immune Response and Disease Progression

Publicado en:Plos One. 11 (5): - 2016-01-01 11(5), DOI: 10.1371/journal.pone.0155245

Autores: Egana-Gorrono, Lander; Guardo, Alberto C.; Bargallo, Manel E.; Planet, Evarist; Vilaplana, Elisenda; Escriba, Tuixent; Perez, Inaki; Maria Gatell, Josep; Garcia, Felipe; Arnedo, Mireia; Plana M, Montserrat;HIV Controllers Consortium AIDS

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The relationship between host microRNAs (miRNA), viral control and immune response has not yet been elucidated in the field of HIV. The aim of this study was to assess the differential miRNA profile in CD8+ T-cells between HIV-infected individuals who differ in terms of viral replication control and immune response.miRNA profile from resting and CD3/CD28-stimulated CD8+ T-cells from uninfected individuals (HIV-, n = 11), Elite Controllers (EC, n = 15), Viremic Controllers (VC, n = 15), Viremic Progressors (VP, n = 13) and HIV-infected patients on therapy (ART, n = 14) was assessed using Affymetrix miRNA 3.1 arrays. After background correction, quantile normalization and median polish summarization, normalized data were fit to a linear model. The analysis comprised: resting samples between groups; stimulated samples between groups; and stimulated versus resting samples within each group. Enrichment analyses of the putative target genes were perfomed using bioinformatic algorithms.A downregulated miRNA pattern was observed when resting samples from all infected groups were compared to HIV-. A miRNA downregulation was also observed when stimulated samples from EC, ART and HIV- groups were compared to VP, being hsa-miR-4492 the most downregulated. Although a preferential miRNA downregulation was observed when stimulated samples were compared to the respective resting samples, VP presented a differential miRNA expression pattern. In fact, hsa-miR-155 and hsa-miR-181a were downregulated in VP whereas in the other groups, either an upregulation or no differences were observed after stimulation, respectively. Overall, functional enrichment analysis revealed that the predicted target genes were involved in signal transduction pathways, metabolic regulation, apoptosis, and immune response.Resting CD8+ T-cells do not exhibit a differential miRNA expression between HIV-infected individuals but they do differ from non-infected individuals. Moreover, a specific miRNA pattern is present in stimulated CD8+ T-cells from VP which could reflect a detrimental pattern in terms of CD8+ T-cell immune response.

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