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细胞角蛋白8(KRT-8)水平在丙型肝炎病毒(HCV)感染引起的肝癌患者体内及在HCV感染细胞培养中均明显上升,与肝病进展密切相关,但KRT-8是否对HCV复制产生影响并不清楚。本文利用KRT-8高表达质粒和特异性sh RNA分析其在细胞培养中对HCV复制的影响,并分析低沉默KRT-8后与已知抗HCV药物联合抑制HCV的作用及其对常见HCV耐药突变株的影响。结果显示,胞内KRT-8水平随HCV复制的增加而增加,其高表达能促进HCV的复制,而特异性干扰KRT-8基因表达后,HCV的复制受到抑制。低沉默KRT-8可以增强已知抗HCV药物特拉匹韦抑制HCV复制的作用,且对蛋白酶抑制剂常见耐药突变(A156T和D168V)HCV也具有抑制作用。这提示KRT-8可能是HCV复制的辅助因子,下调KRT-8具有抗HCV的作用及优势。因此,KRT-8有望成为抗HCV药物研发的一个新的宿主靶点。
The level of cytokeratin 8 (KRT-8) in patients with hepatocellular carcinoma (HCC) caused by hepatitis C virus (HCV) infection significantly increased in the culture of HCV infected cells and closely related to the progress of liver disease. However, The impact is not clear. In this paper, KRT-8 high expression plasmid and specific sh RNA analysis of HCV replication in cell culture and analysis of low silencing KRT-8 with known anti-HCV drugs combined with the role of HCV and its resistance to common HCV Effect of drug-mutant strains. The results showed that the level of intracellular KRT-8 increased with the increase of HCV replication, and its high expression can promote the replication of HCV, while the specific interference with KRT-8 gene expression, HCV replication was inhibited. Low silencing of KRT-8 enhances the inhibition of HCV replication by a known anti-HCV drug, telaprevir, and also inhibits HCV, a common protease inhibitor resistant mutation (A156T and D168V). This suggests that KRT-8 may be a cofactor for HCV replication and down-regulate the anti-HCV effect and advantage of KRT-8. Therefore, KRT-8 is expected to become a new target for the development of anti-HCV drugs.