MicroRNA Profile of HCV Spontaneous Clarified Individuals, Denotes Previous HCV Infection

Abstract

Factors involved in the spontaneous cleareance of a hepatitis C (HCV) infection are related to both HCV and the interaction with the host immune system, but little is known about the consequences after a spontaneous resolution. The main HCV extrahepatic reservoir is the peripheral blood mononuclear cells (PBMCs), and their transcriptional profile provides us information of innate and adaptive immune responses against an HCV infection. MicroRNAs regulate the innate and adaptive immune responses, and they are actively involved in the HCV cycle. High Throughput sequencing was used to analyze the miRNA profiles from PBMCs of HCV chronic naïve patients (CHC), individuals that spontaneously clarified HCV (SC), and healthy controls (HC). We did not find any differentially expressed miRNAs between SC and CHC. However, both groups showed similar expression differences (21 miRNAs) with respect to HC. This miRNA signature correctly classifies HCV-exposed (CHC and SC) vs. HC, with the has-miR-21-3p showing the best performance. The potentially targeted molecular pathways by these 21 miRNAs mainly belong to fatty acids pathways, although hippo signaling, extracellular matrix (ECM) interaction, proteoglycans-related, and steroid biosynthesis pathways were also altered. These miRNAs target host genes involved in an HCV infection. Thus, an HCV infection promotes molecular alterations in PBMCs that can be detected after an HCV spontaneous resolution, and the 21-miRNA signature is able to identify HCV-exposed patients (either CHC or SC).

Expression Profiles of Exosomal MicroRNAs from HEV- and HCV-Infected Blood Donors and Patients: A Pilot Study

“…Both (and together with miR-122) were associated with a poor virologic response [43]. In individuals after they spontaneously cleared HCV, miR-21 was reported to be upregulated [44]. However, in another two studies, miR-21 appeared to be HCV induced [45,46].…”

Comparison of methods and characterization of small RNAs from plasma extracellular vesicles of HIV/HCV coinfected patients

“…This deregulation may directly affect the innate antiviral response, liver disease progression, and the response to antiviral therapies. Additionally, HCV can hijacks and manipulates fatty acid flux to create specific lipid-enrichment microenvironments to promote its life cycle 28 , which will be reflected in the EVs content produced by the infected cells. We also identified the well-known miR-122 in plasma exosomes of HIV/HCV patients, which is a highly liver-specific miRNA implicated in fatty acids and cholesterol biosynthesis, among others.…”

“…Qiagen and Norgen kits of exosomes isolated by all the different protocols as previously described 28 . Sequences of the miRNA nucleotides were extracted from the miRBase Release 21 (www.mirba se.org) 37 (Supplementary Table S4).…”

“…Bioinformatic analysis. The miRNA data analysis was performed as previously described 28 . SmRNA data (snRNA, snoRNA, rRNA, and piRNAs) was extracted with Oasis 2 software 36 from trimmed sequences.…”

Insight in miRNome of Long-Term Non-Progressors and Elite Controllers Exposes Potential RNAi Role in Restraining HIV-1 Infection

“…The study of miRNA expression profiles has provided novel strategies to diagnose, to make prognosis, and even to select a concrete treatment for multiple infectious diseases [20][21][22][23]. The present study aims to identify a miRNA expression pattern associated with ECs/LTNPs phenotypes and through the study of their target genes, to get a better insight into the molecular mechanisms implied in limiting viral replication and disease progression.…”