title: MicroRNA Profile in CD8+ T-Lymphocytes from HIV-Infected Individuals: Relationship with Antiviral Immune Response and Disease Progression.
abstract: 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.
authors.affiliation: Group of Genomics and Pharmacogenomics of HIV, AIDS Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Lander
authors.initials: L
authors.lastname: Egaña-Gorroño
authors.affiliation: Immunopathology and Cellular Immunology, AIDS Research Group, Catalan project for the development of an HIV vaccine (HIVACAT), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Alberto C
authors.initials: AC
authors.lastname: Guardo
authors.affiliation: Immunopathology and Cellular Immunology, AIDS Research Group, Catalan project for the development of an HIV vaccine (HIVACAT), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Manel E
authors.initials: ME
authors.lastname: Bargalló
authors.affiliation: School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Evarist
authors.initials: E
authors.lastname: Planet
authors.affiliation: Group of Genomics and Pharmacogenomics of HIV, AIDS Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain.|Department of Systems Biology, University of Vic-Central University of Catalonia, Vic, Spain.
authors.forename: Elisenda
authors.initials: E
authors.lastname: Vilaplana
authors.affiliation: Group of Genomics and Pharmacogenomics of HIV, AIDS Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Tuixent
authors.initials: T
authors.lastname: Escribà
authors.affiliation: Department of Infectious Diseases, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.
authors.forename: Iñaki
authors.initials: I
authors.lastname: Pérez
authors.affiliation: Department of Infectious Diseases, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Gatell
authors.affiliation: Department of Infectious Diseases, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: García
authors.affiliation: Group of Genomics and Pharmacogenomics of HIV, AIDS Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Arnedo
authors.affiliation: Immunopathology and Cellular Immunology, AIDS Research Group, Catalan project for the development of an HIV vaccine (HIVACAT), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Plana M
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007109:Immunity / Q000187:drug effects; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results
chemical_list: D019380:Anti-HIV Agents; D035683:MicroRNAs