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P-8 EXTRACELLULAR VESICLE-DERIVED MICRORNA SIGNATURE IN HCV AND HCV/HIV PATIENTS WITH DIFFERENT STAGES OF LIVER FIBROSIS
Victoria Cairoli1, Daniel Valle Millares2, Pablo Ryan3, Lourdes Dominguez4, Luz Martín-Carbonero5, Beatriz Ameigeiras6, Verónica Briz2, Amanda Fernandez Rodriguez2,7, Ma Victoria Preciado1, Pamela Valva1
1 Multidisciplinary Institute for Pediatric Pathology Research (Imipp-Conicet-Gcba), Buenos Aires, Argentina
2 National Microbiology Center, Instituto de Salud Carlos III, Madrid, España
3 Infectious Diseases Department, Hospital Universitario Infanta Leonor, Madrid, España
4 HIV Unit. Internal Medicine Service. Instituto de Investigación Hospital 12 de Octubre (I+12), Madrid, España
5 La Paz Hospital Research Institute (Idipaz), Madrid, España
6 Hepatic Unit, Hospital Ramos Mejía, Buenos Aires, Argentina
7 Alfonso X El Sabio University, Villanueva de la Cañada, Madrid, España
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        "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0001">Introduction and Objectives</span><p id="spara001" class="elsevierStyleSimplePara elsevierViewall">Extracellular vesicles &#40;EVs&#41; are essential players in cell communication&#44; and their cargo modulates the receptor cell response&#46; MicroRNAs &#40;miRNAs&#41; proved to modulate the immune response both in physiological and pathological conditions&#46; Hepatitis C &#40;HCV&#41; and Human Immunodeficiency &#40;HIV&#41; virus infection could modify EVs miRNA content and&#44; therefore&#44; the immune response&#46; This study aimed to analyze the significant differentially expressed &#40;SDE&#41; EVs-derived miRNAs between HCV and HCV&#47;HIV-infected patients&#44; analyze differences according to liver fibrosis stages and explore the associated molecular pathways&#46;</p></span> <span id="abss0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0002">Materials and Methods</span><p id="spara002" class="elsevierStyleSimplePara elsevierViewall">Plasma from 21 chronic HCV and 29 HCV&#47;HIV patients were analyzed&#46; EVs were isolated and total EV-containing RNA enriched with small RNAs was high-throughput sequenced &#40;1&#8239;&#215;&#8239;50&#41;&#46; Raw reads were analyzed with Fastqc and trimmed with Cutadapt&#46; Human-miRNA identification was performed with miRDeep2&#46; R package edgeR was used to detect SDE miRNAs between groups and <span class="elsevierStyleItalic">in silico</span> miRNA target prediction was performed with DIANA-mirPath&#46;</p></span> <span id="abss0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Results</span><p id="spara003" class="elsevierStyleSimplePara elsevierViewall">HCV patients &#91;54 years &#40;46&#46;5&#59; 62&#46;5&#41;&#44; 52&#46;4&#37; F&#8805;2&#93; showed 38 SDE miRNAs compared with the HCV&#47;HIV group &#91;50 years &#40;45&#59; 53&#41;&#44; 22&#46;58 &#37; F&#8805;2&#93; that modulate pathways related to fatty acids biosynthesis&#44; extracellular matrix interaction and viral carcinogenesis&#46; Regarding fibrosis&#44; HCV patients with F&#60;2 showed downregulation of hsa-miR-3615 &#40;log<span class="elsevierStyleInf">2</span>FC&#61;-0&#46;92&#44; p&#61;0&#46;039&#41;&#44; which modulates genes involved in the cell cycle and the mRNA surveillance pathway&#46; On the other hand&#44; HCV&#47;HIV patients with F&#60;2 had 13 SDE miRNAs compared with F&#8805;2&#46; Among them&#44; hsa-miR-122-5p &#40;downregulated&#41; and hsa-miR-328-3p &#40;upregulated&#41; showed the most significant differences &#40;log<span class="elsevierStyleInf">2</span>FC&#61;-1&#46;22&#44; p&#61;0&#46;034&#44; log2FC&#61;1&#46;33&#44; p&#61;0&#46;042&#44; respectively&#41;&#46; Together&#44; they regulate genes involved in cancer-related pathways and fatty acid metabolism&#46;</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Conclusions</span><p id="spara004" class="elsevierStyleSimplePara elsevierViewall">Differentially expressed EVs-derived miRNAs in HCV and HCV&#47;HIV chronic infection and in different stages of liver fibrosis were observed&#46; The specific miRNA signature of each liver fibrosis stage may elucidate potential mechanisms involved in the clinical evolution of these patients and the identification of biomarkers of unfavorable progression&#46;</p></span>"
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ISSN: 16652681
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