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 (miR‑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 miR‑155 in PBMCs, serum and liver tissues of GT4‑HCV‑infected patients. miR‑155 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 miR‑155 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 miR‑155 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 miR‑155 expression. In addition, serum miR‑155 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, miR‑155 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.