Expression signature of microRNA-155 in hepatitis C virus genotype 4 infection

Abstract

Hepatits C virus (HCV) genotype 4 (GT4) shows low treatment response rates and discrepancies when compared to other genotypes. However, the reason underlying these discrepancies remains unclear due to the limited number of studies on GT4. microRNA-155 () is a noteworthy example of a discrepancy in GT4, as it was found to be upregulated in genotypes 1, 2 and 3 HCV infection, but downregulated in GT4-HCV-infected peripheral blood mononuclear cells (PBMCs). The present study aimed to investigate the expression of in PBMCs, serum and liver tissues of GT4-HCV-infected patients. expression was assessed using reverse transcription-quantitative polymerase chain reaction in GT4-HCV-infected PBMCs, serum and liver tissues, as well as GT2- and GT4-infected Huh7 cells, and compared to the healthy controls. There was no difference in expression observed between naïve GT4-HCV patients and healthy controls in the PBMCs and serum. In HCV-infected liver tissues, however, a significant downregulation was observed. The unique expression pattern during GT4 infection was confirmed in the infected Huh7 cell lines when compared to GT2 infection. Clinical data showed a positive correlation between liver transaminases and serum expression. In addition, serum expression was significantly lower in naïve non-responders (NRs) than naïve sustained virological responders (SVRs), and in post-treatment NRs compared to post-treatment SVRs. In conclusion, was not only proven to be a genotype-specific microRNA that is not induced during GT4-HCV infection, but also a good prognostic factor and predictor of response to treatment enabling a non-invasive differentiation between NRs and SVRs during GT4-HCV infection.

Hepatic miR‐126 is a potential plasma biomarker for detection of hepatitis B virus infected hepatocellular carcinoma

“…The tumor suppressor miRNA miR‐15a, which is usually down regulated or deleted in prostate cancer found to be overexpressed in liver tissue of HCC patients but again we failed to correlate the expression level of this miRNA in plasma. Such incongruities in miRNA expression patterns between serum and tissue have been reported previously, which again supported that circulating miRNAs might not always be shed from diseased organ. Recently, Tewari group has also documented that among 79 circulating miRNAs identified so far as biomarkers of different solid tumors, 47 circulating miRNAs are over expressed in hematological cells .…”

In vitro knock‐out of miR‐155 suppresses leukemic and HCV virus loads in pediatric HCV‐4–associated acute lymphoid leukemia: A promising target therapy

“…miR‐155 has a critical prognostic role in HCV infection, leukemia, and lymphomas . miR‐155 expression is one of the discrepancies in HCV genotype 4 infections, as it does not vary in polymorph nuclear cells (PMNCs) compared to healthy controls, unlike its expression in HCV genotypes 1, 2, and 3 infections . The different expression of miR‐155 may affect the prognosis and may explain the resistance to the treatment pattern of HCV genotype 4 .…”

“…miR‐155 expression is one of the discrepancies in HCV genotype 4 infections, as it does not vary in polymorph nuclear cells (PMNCs) compared to healthy controls, unlike its expression in HCV genotypes 1, 2, and 3 infections . The different expression of miR‐155 may affect the prognosis and may explain the resistance to the treatment pattern of HCV genotype 4 . On the other hand, studies that investigated the role of miR‐155 in CML and AML demonstrated that it is upregulated in cells and circulating exosomes .…”

An update on the role of miRNA-155 in pathogenic microbial infections

“…Over-expression of miR-155 was found to strengthen defenses against viruses by counteracting the immunosuppressive effect of IL-10 or TGF-b on TLR3-induced antiviral activity [27]. However, a down-regulation of miR-155 has been reported in PBMCs infected with genotype 4 (GT4) but not GT1, 2 or 3 HCV [28]. Therefore, miR-155 appears to respond in a genotype-specific way.…”

“…Therefore, miR-155 appears to respond in a genotype-specific way. It was also found to be a satisfactory prognostic factor and predictor of response to treatment with pegylated interferon/ribavirin, enabling differentiation between naïve non-responders and naïve sustained virological responders during GT4-HCV infection [28]. El-Ekiaby et al [29] reported evidence about GT4-HCV infection impairing the induction of miR-146 and -155 by IFN-a when TLR7 is agonized, which promotes the release of IFN-a.…”