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Inhibition of hepatitis C virus genotype 4 replication using siRNA targeted to the viral core region and the CD81 cellular receptor.
Cell Stress and Chaperones ( IF 3.8 ) Pub Date : 2020-02-14 , DOI: 10.1007/s12192-020-01077-1
Reem M Aljowaie 1 , Fahad N Almajhdi 1 , Hebatallh H Ali 2 , Mohammad S El-Wetidy 2 , Medhat K Shier 2, 3
Affiliation  

Hepatitis C virus (HCV) is one of the most important causative agents of hepatitis worldwide. The current study aimed to evaluate the silencing effect of the small interference RNA (siRNA) molecules designed against the core region of HCV genotype 4 (HCV-4) and the CD81 gene, which is the cellular receptor for HCV in the human hepatocytes. RT-PCR was used to measure the changes in both the viral HCV core and the cellular CD81 genes induced by the specific siRNA molecules. Additionally, the fluctuations in either the viral or the cellular proteins of the target regions were tested by flow cytometry and immunofluorescence. The results showed the effectiveness of the used siRNA molecules against the target genes in either RNA or protein levels. The effect of 100 nM of siCD81 and 40 nM of siCore was more evident at 24 and 48 h post-transfection. The combination of the two siRNA molecules resulted in an extra inhibitory effect of the HCV core at both the RNA (85.6%) and protein (98.5%) levels. The current study suggested that targeting of the CD81 cellular receptor and/or the viral HCV core region by the small interference molecules might be a suitable choice in the suppression of HCV-4 replication. This might assist the development of new antiviral medications and provides a new alternative strategy for the targeting and treatment of HCV genotype 4.

中文翻译:

使用靶向病毒核心区域和CD81细胞受体的siRNA抑制丙型肝炎病毒基因型4复制。

丙型肝炎病毒(HCV)是全世界肝炎最重要的病原体之一。当前的研究旨在评估针对HCV基因型4(HCV-4)和CD81基因的核心区域设计的小干扰RNA(siRNA)分子的沉默效果,该基因是人类肝细胞中HCV的细胞受体。RT-PCR用于测量病毒HCV核心和特定siRNA分子诱导的细胞CD81基因的变化。另外,通过流式细胞术和免疫荧光测试靶区域的病毒或细胞蛋白中的波动。结果显示了所用的siRNA分子针对RNA或蛋白质水平的靶基因的有效性。转染后24和48 h,100 nM siCD81和40 nM siCore的作用更为明显。两种siRNA分子的组合对HCV核心在RNA(85.6%)和蛋白质(98.5%)上都有额外的抑制作用。当前的研究表明,小的干扰分子靶向CD81细胞受体和/或病毒HCV核心区域可能是抑制HCV-4复制的合适选择。这可能有助于新抗病毒药物的开发,并为靶向和治疗HCV基因型4提供了新的替代策略。当前的研究表明,小的干扰分子靶向CD81细胞受体和/或病毒HCV核心区域可能是抑制HCV-4复制的合适选择。这可能有助于新抗病毒药物的开发,并为靶向和治疗HCV基因型4提供了新的替代策略。当前的研究表明,小的干扰分子靶向CD81细胞受体和/或病毒HCV核心区域可能是抑制HCV-4复制的合适选择。这可能有助于新抗病毒药物的开发,并为靶向和治疗HCV基因型4提供了新的替代策略。
更新日期:2020-02-14
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