Differential expression of interferon-induced microRNAs in patients with chronic hepatitis C virus infection treated with pegylated interferon alpha

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.

Figure 1

Interferon (IFN) induced expression of microRNAs (miR-1, miR-30, miR-128, miR-196, miR-296) in peripheral blood mononuclear cells collected from three healthy individuals after in-vitro treatment with IFN alpha (100 international unit (IU)/ml). Expression of MxA-mRNA was also evaluated. Significant increases, relative to baseline, after in vitro IFN treatment were observed for miR-1, miR-30, miR-128, miR-196, miR-296 and MxA (p < 0.05 using student's T-test).

Figure 2

Fold induction of microRNAs (miR)-1 (Panel A), miR-30 (Panel B), miR-128 (Panel C), miR-196 (Panel D), miR-296 (Panel E) and MxA-mRNA (Panel F) in peripheral blood mononuclear cells collected from all single patients with chronic hepatitis C after interferon treatment.

Figure 3

Fold induction of microRNAs (miR)-1, miR-30, miR-128, miR-196, miR-296 and MxA-mRNA in peripheral blood mononuclear cells collected from patients with chronic hepatitis C after the first injection of interferon. Significant increases, relative to baseline, after IFN treatment were observed for miR-1, miR-30, miR-296 and MxA-mRNA (p < 0.05 using Wilcoxon test).