Abstract
MicroRNAs have been reported to be regulated in different ways in a variety of liver diseases. As a key modulator of cellular function in both innate and adaptive immunity, the role of miR-155 in chronic hepatitis B virus infection remains largely unknown. Here, we investigated the expression and function of miR-155 in chronic hepatitis B (CHB) patients. It was found that miR-155 expression in peripheral blood mononuclear cells (PBMCs) was lower in CHB patients than healthy controls (HC). Among CHB infection, immune-active (IA) patients with abnormal alanine aminotransferase (ALT) levels had relatively higher miR-155 expression in PBMCs and serum than immune-tolerant carriers, but were comparable to inactive carriers. Moreover, there was a positive correlation between miR-155 expression and ALT levels in CHB patients. Particularly, miR-155 expression in natural killer (NK) cells was significantly downregulated in IA patients compared with HC. Inversely, suppressor of cytokine signaling 1 (SOCS1), a target of miR-155, was upregulated in NK cells of IA patients. Overexpression of miR-155 in NK cells from IA patients led to a decrease in SOCS1 expression and an increase of IFN-γ production. Finally, accompanied by the normalization of ALT, miR-155 expression in PBMCs gradually decreased during telbivudine or peg-IFN-α-2a therapy. Interestingly, higher miR-155 expression at baseline was associated with better response to telbivudine therapy, but not peg-IFN-α-2a. In conclusion, our data suggested that miR-155 downregulation in NK cells of IA patients impaired IFN-γ production by targeting SOCS1, which may contribute to immune dysfunction during CHB infection. Additionally, baseline miR-155 expression could predict the treatment response to telbivudine therapy.
Highlights
Hepatitis B virus (HBV) infection causes acute and chronic hepatitis and is a threat to public health across the world
We examined the expression of miR-155 in peripheral blood mononuclear cell (PBMC) and serum samples from all chronic hepatitis B (CHB) patients by real-time RT-PCR
MiR-155 serum levels during various phases of chronic HBV infection were similar to those occurring in PBMCs (Figure 1B, healthy controls (HC) vs IT, p = 0.023; immune activation (IA) vs IT, p = 0.013)
Summary
Hepatitis B virus (HBV) infection causes acute and chronic hepatitis and is a threat to public health across the world. The outcome and pathogenesis of HBV infection is related to the complex interaction between viral activity and host immunity [2]. MicroRNAs (miRNAs) are non-coding RNAs that regulate the expression of multiple genes at the posttranscriptional level by either translational repression or messenger RNA degradation [3]. They play important roles in normal biological processes and have potential as disease biomarkers because they can indicate abnormal functions of particular organs. Many studies have reported that viral infections change host miRNAs profiles, which may affect virus–host interactions and participate in the viral life cycle and pathogenesis [4, 5]. The available evidence indicates that miRNAs are involved in both the HBV life cycle and the development of HBV-associated liver diseases [6]
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