Differential microRNA expression profile between stimulated PBMCs from HIV-1 infected elite controllers and viremic progressors

PLoS One. 2014 Sep 16;9(9):e106360. doi: 10.1371/journal.pone.0106360. eCollection 2014.

Abstract

Background: The emerging relationship between microRNAs (miRNA) and viral-control is a topic of interest in the field of HIV. Host-genome might play an important role in the control of viremia. The aim of this study was to assess the specific miRNA profile that could contribute to the control of HIV replication in Elite Controllers.

Results: After adequate normalization, expression profile of 286 human miRNAs (hsa-miR) was evaluated in phytohaemagglutinin-stimulated PBMCs from 29 individuals classified in 4 groups: 8 elite controllers (EC; viral load <50 cp/ml without treatment), 8 viremic progressors (VP; VL>5000 cp/ml without treatment), 8 patients under antiretroviral treatment (ART; VL<200 cp/ml) and 5 uninfected individuals (HIV-) through TaqMan Array Human microRNA Cards v3.0. A differential expression pattern consisting of 23 miRNAs became significantly different when comparing EC and VP. Profiling analysis segregated the population in two different blocks: while EC and HIV- clustered together in the same block (EC/HIV-_block 1), VP and ART individuals clustered together in a second block (VP/ART_block 2). Two inversely expressed miRNA patterns were determined within those two blocks: a set of 4 miRNAs (hsa-miR-221, -27a, -27b and -29b) was up-expressed in EC/HIV-_block and down-expressed in VP/ART_block while 19 miRNAs were down-expressed in block 1 and up-expressed in block 2. Differential miRNAs were successfully validated through individual RT-qPCR assays.

Conclusions: Profile in EC resembled HIV- and differentially clusters with VP and ART. Therefore, differential clustering does not rely on undetectable viremia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • Case-Control Studies
  • Cluster Analysis
  • Disease Progression
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • HIV Infections / drug therapy
  • HIV Infections / genetics*
  • HIV Infections / virology*
  • HIV-1*
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Reproducibility of Results
  • Viral Load
  • Viremia*
  • Young Adult

Substances

  • MicroRNAs

Grants and funding

This work was partially supported by HIVACAT (HIV Vaccine Research and Development Programme in Catalonia), Fundación para la Investigación y la Prevención del Sida en España (FIPSE 09), Fondo Europeo para el Desarrollo Regional (FEDER), Fondo de Investigación Sanitaria FIS, FIS PI070291, PI12/00969, Red de Investigación en Sida (RIS), Instituto de Salud Carlos III (ISCIII-RETIC RD06/0006/0000). M. Arnedo and M. Plana are researchers from the Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS) and are supported by the Spanish Health of the ISCIII (Instituto de SaludCarlos III) and the Health Department of the Catalan Government (Generalitat de Catalunya). L. Egaña-Gorroño is a recipient of a pre-doctoral grant from the ISCIII (FI10/00174). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.