Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
J Med Virol. 2014 Apr;86(4):687-94. doi: 10.1002/jmv.23873. Epub 2013 Dec 30.
Hepatitis B virus (HBV) infection can result in fatal liver diseases, including cirrhosis or liver failure, and its replication and pathogenesis depend on the critical interplay between viral and host factors. This study investigated HBV replication-related host proteins and the effect of candidate proteins on HBV replication. Isobaric tags for relative and absolute quantitation (iTRAQ) were used to measure HBV replication-related proteins in HepG2 cells and HepG2.2.15 cells. KRT8 was up-regulated in HepG2.2.15 cells but not in HepG2 cells, and KRT8 was overexpressed in an HBV-infected patient's liver tissue. This result suggested that KRT8 is involved in HBV replication. To further clarify the relationship between KRT8 and HBV replication, KRT8 gene expression was inhibited by siRNA. The silencing of KRT8 mildly suppressed HBV replication. Moreover, overexpressed KRT8 significantly increased HBV replication, and the inhibition of HBV DNA did not suppress KRT8 expression. Thus, the host protein KRT8 is involved in the replication of HBV DNA, and it dramatically enhances HBV replication.
乙型肝炎病毒 (HBV) 感染可导致致命的肝脏疾病，包括肝硬化或肝功能衰竭，其复制和发病机制取决于病毒和宿主因素的关键相互作用。本研究调查了与 HBV 复制相关的宿主蛋白，以及候选蛋白对 HBV 复制的影响。采用相对和绝对定量同位素标记 (iTRAQ) 技术测量 HepG2 细胞和 HepG2.2.15 细胞中与 HBV 复制相关的蛋白。在 HepG2.2.15 细胞中 KRT8 上调，但在 HepG2 细胞中没有上调，并且在 HBV 感染患者的肝组织中 KRT8 过表达。这表明 KRT8 参与了 HBV 复制。为了进一步阐明 KRT8 与 HBV 复制之间的关系，通过 siRNA 抑制 KRT8 基因表达。KRT8 的沉默轻度抑制了 HBV 复制。此外，过表达的 KRT8 显著增加了 HBV 复制，并且抑制 HBV DNA 不能抑制 KRT8 表达。因此，宿主蛋白 KRT8 参与 HBV DNA 的复制，并显著增强 HBV 复制。
