Riad Sarah Ehab, El-Ekiaby Nada, Mekky Radwa Yehia, Ahmed Rasha, El Din Mohammad Ahmed Mohey, El-Sayed Mohammad, Abouelkhair Mahmoud Mohammad, Salah Ayman, Zekri Abdel Rahman, Esmat Gamal, Abdelaziz Ahmed Ihab
The Molecular Pathology Research Group, Department of Pharmacology and Toxicology, German University in Cairo, New Cairo 11835, Egypt.
Departments of Endemic Medicine and Hepatology and Egypt.
Biomed Rep. 2015 Jan;3(1):93-97. doi: 10.3892/br.2014.373. Epub 2014 Oct 22.
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.
丙型肝炎病毒(HCV)基因4型(GT4)与其他基因型相比,治疗反应率较低且存在差异。然而,由于对GT4的研究数量有限,这些差异背后的原因仍不清楚。微小RNA-155(miR-155)是GT4差异的一个值得注意的例子,因为它在1、2和3型HCV感染中被发现上调,但在GT4-HCV感染的外周血单核细胞(PBMC)中下调。本研究旨在调查GT4-HCV感染患者的PBMC、血清和肝组织中miR-155的表达。使用逆转录定量聚合酶链反应评估GT4-HCV感染的PBMC、血清和肝组织以及GT2和GT4感染的Huh7细胞中miR-155的表达,并与健康对照进行比较。在未经治疗的GT4-HCV患者与健康对照的PBMC和血清中,未观察到miR-155表达的差异。然而,在HCV感染的肝组织中,观察到显著下调。与GT2感染相比,在感染的Huh7细胞系中证实了GT4感染期间独特的miR-155表达模式。临床数据显示肝转氨酶与血清miR-155表达之间呈正相关。此外,未经治疗的无反应者(NRs)的血清miR-155表达明显低于未经治疗的持续病毒学应答者(SVRs),并且在治疗后NRs与治疗后SVRs相比也是如此。总之,miR-155不仅被证明是一种在GT4-HCV感染期间不被诱导的基因型特异性微小RNA,而且是一个良好的预后因素和治疗反应的预测指标,能够在GT4-HCV感染期间对NRs和SVRs进行非侵入性区分。