Abstract
There have been reports of in-vitro interferon (IFN)-mediated antiviral activity against the hepatitis C virus (HCV) through microRNAs (miRNAs). The main aim of this study was to evaluate the expression of several miRNAs (miR-1, miR-30, miR-128, miR-196, miR-296) in peripheral blood mononuclear cells (PBMCs) from healthy individuals after in vitro IFN-treatment and in PBMCs from patients with chronic hepatitis C (CHC) before and 12 hours after the first injection of pegylated IFN alpha. We demonstrated that expression of these miRNAs could be recorded in PBMCs collected from healthy individuals before and after in-vitro IFN alpha treatment. Our analysis revealed that the levels of expression of all miRNAs investigated in patients with CHC were different to those in healthy individuals. When levels of the miRNAs were measured 12 hours after the first IFN injection, increases in expression levels of IFN-induced miRNAs were observed in 25-50% of patients, depending on the type of miRNA examined. No correlations were observed between HCV viral load, alanine aminotransferase status and expression of miRNA. Together these findings suggest that: (i) IFN alpha in-vitro treatment of PBMCs leads to a transcriptional induction of all miRNAs investigated; (ii) miRNAs can be induced differentially by IFN treatment in patients with HCV. Given the importance of miRNAs in defending the host against virus infections, it is possible that IFN-induced miRNAs may represent an important determinant of the clinical outcome of IFN therapy in HCV infection.
Highlights
MicroRNAs are an important class of small non-coding RNA molecules that have recently come to prominence as critical regulators in a wide array of mechanisms of cell physiology
Baseline and in vitro IFN alpha induced expression of microRNAs in peripheral blood mononuclear cells (PBMCs) collected from healthy individuals As there are no published reports about expression profiles of miR-1, miR-30, miR-128, miR-196, and miR-296 in PBMCs from normal individuals, our first investigation was of their expression in PBMCs from healthy volunteers using real-time quantitative reverse transcription polymerase chain reaction (RT-PCR)
We examined whether leukocyte IFN alpha could stimulate in-vitro expression of the miRNAs listed above as previously reported for IFN beta
Summary
MicroRNAs (miRNAs) are an important class of small non-coding RNA molecules that have recently come to prominence as critical regulators in a wide array of mechanisms of cell physiology. There is increasing evidence that miRNAs may have an important function in viral replication and may be used by host cells to control viral infection [1,2]. Interferon (IFN) beta has been reported as modulating the expression of several cellular miRNAs that are capable of inhibiting hepatitis C virus (HCV) replication and infection, because they have sequence-predicted targets within the HCV genomic RNA. Pederson and co-authors reported that IFN beta downregulated the expression of miR-122, which has been implicated in the control of HCV RNA replication. This finding could lead to a better understanding of the factors involved in the failure of IFN therapy in patients with chronic hepatitis C (CHC). Environmental and host factors, a sustained virological response is achieved in about 50% of patients infected with HCV genotype 1 and in about 80% of patients infected with HCV genotypes 2 or 3; more importantly, despite extensive examination of the biological and clinical effects of IFN in patients with CHC, the prediction of treatment responses in individual patients still remains difficult [5,6]
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