EV-derived miRNA signature in HCV+ and HCV+/HIV+ patients with different stages of liver fibrosis

CAIROLI V; VALLE MILLARES D; RYAN P; DOMINGUEZ L; MARTÍN-CARBONERO L; AMEIGEIRAS B; BRIZ V; FERNANDEZ RODRIGUEZ A; PRECIADO MV; VALVA P

Congreso; ALEH 2022; 2022

ALEH

INTRODUCTION: Extracellular vesicles (EVs) are essential players in cell communication, and their cargo modulates the receptor cell response. MicroRNAs (miRNAs) proved to modulate the immune response both in physiological and pathological conditions. Hepatitis C (HCV) and Human Immunodeficiency (HIV) viruses’ infection could modify EVs miRNA content and therefore, the immune response. OBJECTIVE: To analyze the significant differentially expressed (SDE) EVs-derived miRNAs of HCV and HCV/HIV infected patients with different stages of liver fibrosis and to explore the associated molecular pathways.METHODS: Plasma from 21 chronic HCV and 29 HCV/HIV patients were analyzed. EVs were isolated and total EV-containing RNA enriched with small RNAs was high-throughput sequenced (1x50). Raw reads were analyzed with Fastqc and trimmed with Cutadapt. Human-miRNA identification was performed with miRDeep2. R package edgeR was used to detect SDE miRNAs between groups and in silico miRNA target prediction was performed with DIANA-mirPath.RESULTS: HCV patients [54 years (46.5; 62.5), 52.4% F≥2] showed 38 SDE miRNAs compared with the HCV/HIV group [50 years (45; 53), 22.58 % F≥2] that modulate pathways related to fatty acids biosynthesis, extracellular matrix (ECM) interaction and viral carcinogenesis. Regarding fibrosis, HCV patients with no significant fibrosis showed downregulation of hsa-miR-3615 (log2FC=-0.92, p=0.039) which modulates genes involved in cell cycle and the mRNA surveillance pathway. On the other hand, HCV/HIV patients with F