Differential MicroRNA Expression Profile between Stimulated PBMCs from HIV-1 Infected Elite Controllers and Viremic Progressors

Abstract

BackgroundThe 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 ControllersResultsAfter 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.ConclusionsProfile in EC resembled HIV- and differentially clusters with VP and ART. Therefore, differential clustering does not rely on undetectable viremia.

MicroRNA and HIV

“…Editorial microRNAs (miRNAs) are non-coding RNAs (19-25 nucleotides) that regulate gene expression at transcriptional level [1][2][3][4][5][6]. They bind to messenger RNAs (mRNA), generally by imperfect base alignment in 3'-UTR region, and cause translational repression, mRNA destabilization and/or mRNA direct destruction [3][4][5].…”

“…They bind to messenger RNAs (mRNA), generally by imperfect base alignment in 3'-UTR region, and cause translational repression, mRNA destabilization and/or mRNA direct destruction [3][4][5]. It has been described that miRNAs can induce heterochromatin formation as well as it can induce protein translations sometimes [4].…”

“…It has been described that miRNAs can induce heterochromatin formation as well as it can induce protein translations sometimes [4]. There are over 2500 annotated and more than 60% of human genes are regulated by them [1,3,4]. A particular miRNA can regulate multiple mRNAs.…”

“…miRNAs have been used as biomarkers because they are stable, present in plasma, and their detection is easy [8]. It has been demonstrated that their analysis allows to know the immune status of patients with cancer or viral infections [2,3,9,10]. miRNAs are involved in different cellular processes (differentiation, development, death) and their deregulation is related to infectious diseases, cancer or altered immune response [4,[10][11][12].…”

“…[3][4][5][6]8,10,[13][14][15][16][17][18] For instance, miR-155 regulates T cell differentiation as well as contributes to Treg development [15]. miR-223 has a role during infection, inflammation as well as hematopoietic cell differentiation [16].…”