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

Abstract

Background 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 differ ential miRNA profile in CD8+ T-cells between HIV-infected individuals who differ in terms of viral replication control and immune response. Methods miRNA profile from resting and CD3/CD28-stimulated CD8+ T-cells from uninfected individ uals (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 com prised: resting samples between groups; stimulated samples between groups; and stimu lated versus resting samples within each group. Enrichment analyses of the putative target genes were perfomed using bioinformatic algorithms. PLOS ONE | DOI:10.1371/journal.pone.0155245 May 12, 2016 1 / 19 a11111 OPEN ACCESS Citation: Egaña-Gorroño L, Guardo AC, Bargalló ME, Planet E, Vilaplana E, Escribà T, et al. (2016) MicroRNA Profile in CD8+ T-Lymphocytes from HIV Infected Individuals: Relationship with Antiviral Immune Response and Disease Progression. PLoS ONE 11(5): e0155245. doi:10.1371/journal. pone.0155245 Editor: Mathias Lichterfeld, Massachusetts General Hospital, UNITED STATES Received: February 3, 2016 Accepted: April 26, 2016 Published: May 12, 2016 Copyright: © 2016 Egaña-Gorroño et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: Raw data and corrected, quantile and median polished normalized data from Affymetrix miRNA 3.1 strip arrays were deposited with the Gene Expression Omnibus (GEO: NCBI Gene Expression Omnibus (GEO) http://www. ncbi.nlm.nih.gov/geo/) and are accessible at Series record number GSE71650. Funding: 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 Results A downregulated miRNA pattern was observed when resting samples from all infected groups were compared to HIV-. A miRNA downregulation was also observed when stimu lated 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. Conclusions 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 pat tern is present in stimulated CD8+ T-cells from VP which could reflect a detrimental pattern in terms of CD8+ T-cell immune response