Identification of Keratin 23 as a Hepatitis C Virus-Induced Host Factor in the Human Liver
Identification of Keratin 23 as a Hepatitis C Virus-Induced Host Factor in the Human Liver
复制标题
DOI：
10.3390/cells8060610
复制
发表时间：
2019-06-01
期刊：
影响因子：
6
通讯作者：
Steinmann, Eike
中科院分区：
文献类型：
--
作者：
Kinast, Volker;Leber, Stefan L.;Steinmann, Eike
角蛋白形成中间丝，为许多组织提供结构支持。据报道，多个角蛋白家族成员与多种病因的肝病进展相关。例如，角蛋白23（KRT 23）被报道为应激诱导蛋白，其表达水平与肝脏疾病的严重程度相关。丙型肝炎病毒（HCV）是一种人类病原体，可引起慢性肝病，包括纤维化、肝硬化和肝细胞癌。然而，KRT 23与丙型肝炎病毒（HCV）感染之间的联系以前尚未报道。在这项研究中，我们研究了慢性丙型肝炎（CHC）患者肝活检数据集和实验感染HCV的原代人肝细胞以及肝癌细胞中的KRT 23 mRNA水平。有趣的是，在这些样本中，我们观察到HCV依赖性mRNA水平的增加。重要的是，患者血浆中的KRT 23蛋白水平在病毒清除后降低。KRT 23的异位表达增强了HCV感染;然而，CRIPSPR/Cas9介导的敲除并没有显示出改变的复制效率。综上所述，我们的研究将KRT 23确定为丙型肝炎病毒的新型病毒诱导宿主因子。
Keratin proteins form intermediate filaments, which provide structural support for many tissues. Multiple keratin family members are reported to be associated with the progression of liver disease of multiple etiologies. For example, keratin 23 (KRT23) was reported as a stress-inducible protein, whose expression levels correlate with the severity of liver disease. Hepatitis C virus (HCV) is a human pathogen that causes chronic liver diseases including fibrosis, cirrhosis, and hepatocellular carcinoma. However, a link between KRT23 and hepatitis C virus (HCV) infection has not been reported previously. In this study, we investigated KRT23 mRNA levels in datasets from liver biopsies of chronic hepatitis C (CHC) patients and in primary human hepatocytes experimentally infected with HCV, in addition to hepatoma cells. Interestingly, in each of these specimens, we observed an HCV-dependent increase of mRNA levels. Importantly, the KRT23 protein levels in patient plasma decreased upon viral clearance. Ectopic expression of KRT23 enhanced HCV infection; however, CRIPSPR/Cas9-mediated knockout did not show altered replication efficiency. Taken together, our study identifies KRT23 as a novel, virus-induced host-factor for hepatitis C virus.