The impact of chronic hepatitis C infection on cholesterol metabolism in PBMCs is associated with microRNA-146a expression

Abstract

Chronic hepatitis C (CHC) infection is known to induce important changes in host cholesterol metabolism. MicroRNAs (miRNAs) regulate the expression of many genes and, in consequence, control various processes, including human metabolism and response to viral infection. Recently, the alteration of the immune-associated miR-146a, which is abundantly present in peripheral blood mononuclear cells (PBMCs), was found in some viral infections. The study aimed to analyse the influence of hepatitis C virus (HCV) infection on miR-146a expression in PBMCs in vivo and in vitro, as well as to assess the possible impact of miR-146a alteration on the intracellular cholesterol level in PBMCs. Blood samples collected from 42 healthy donors and 72 CHC patients were the source of materials. HCV RNA, intracellular cholesterol level and miR-146a expression were determined in PBMCs, as well as HCV genotype and interferon (IFN)α concentration in sera. The influence of miR-146a inhibition on cholesterol expression in PBMCs was analysed in vitro after transient cell transfections with mirVana™ anti-miR-146a Inhibitor. Our data demonstrated an alteration of miR-146a and intracellular cholesterol expression in PBMCs and of IFNα concentration in sera of genotype 1, HCV-infected patients compared to the healthy donors. Also, in cultured PBMCs, miR-146a expression and intracellular cholesterol level were significantly decreased in CHC patients compared to the healthy donors. In vitro blockage of miR-146a expression in PBMCs of CHC patients greatly impaired intracellular cholesterol expression. In these conditions, miR-146a expression was positively correlated with the intracellular cholesterol level. These results suggest that genotype 1 HCV infection may alter miR-146a expression in PBMCs and, consequently, contribute to the observed dysregulation of cholesterol synthesis.

miRNAs regulate immune response and signaling during hepatitis C virus infection

“…Similar to miR-155, miR-146a is abundant in peripheral blood mononuclear cells and regulates the inflammatory and immune responses [ 28 ]. It has recently been reported that miR-146 was upregulated in HCV-infected cells, human primary hepatocytes and liver tissue of chronic hepatitis C infection patients [ 28 ].…”

“…Similar to miR-155, miR-146a is abundant in peripheral blood mononuclear cells and regulates the inflammatory and immune responses [ 28 ]. It has recently been reported that miR-146 was upregulated in HCV-infected cells, human primary hepatocytes and liver tissue of chronic hepatitis C infection patients [ 28 ]. On the other hand, decreased miR-146a expression has also been observed in peripheral blood mononuclear cells from patients with chronic hepatitis C. This can partially be explained as the studies analysed patients infected with different genotype HCV.…”

Depletion of MicroRNA-373 Represses the Replication of Hepatitis C Virus via Activation of Type 1 Interferon Response by Targeting IRF5

“… 35 HCV infection was also shown to boost the expression of miR-146, leading to an alteration of IFN concentrations in sera following HCV infection. 36 Similarly, other miRNAs, such as miR-130 and miR-21, have been described as participating in inflammatory and immune responses to HCV infection. 37 , 38 Based on the present findings in this study, we further accessed if miR-373 and IRF5 contribute to activation of type 1 IFN.…”

The Correlation between miR-122 and Lipoprotein Lipase Expression in Chronic Hepatitis C Patients

“…We followed the methods of Sidorkiewicz et al 2017 [ 12 ]. Serum total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglycerides (TG) were measured enzymatically in Olympus AU 640 and the kits of Olympus.…”