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首页> 外文期刊>Microbiology and Immunology >Interaction of the hepatitis B virus X protein with the lysine methyltransferase SET and MYND domain-containing 3 induces activator protein 1 activation
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Interaction of the hepatitis B virus X protein with the lysine methyltransferase SET and MYND domain-containing 3 induces activator protein 1 activation

机译：乙型肝炎病毒X蛋白与赖氨酸甲基转移酶SET和含MYND结构域3的相互作用诱导激活蛋白1激活

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摘要

Hepatitis B virus (HBV) is a widespread human pathogen that often causes chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The detailed mechanisms underlying HBV pathogenesis remain poorly understood. The HBV X protein (HBx) is a multifunctional regulator that modulates viral replication and host cell functions, such as cell cycle progression, apoptosis and protein degradation through interaction with a variety of host factors. Recently, the nonstructural protein 5A (NS5A) of hepatitis C virus has been reported to interact with methyltransferase SET and MYND domain-containing 3 (SMYD3), which is implicated in chromatin modification and development of cancer. Because HBx shares fundamental regulatory functions concerning viral replication and pathogenesis with NS5A, it was decided to examine whether HBx interacts with SMYD3. In the present study, it was demonstrated by co-immunoprecipitation analysis that HBx interacts with both ectopically and endogenously expressed SMYD3 in Huh-7.5 cells. Deletion mutation analysis revealed that the C-terminal region of HBx (amino acids [aa] 131-154) and an internal region of SMYD3 (aa 269-288) are responsible for their interaction. Immunofluorescence and proximity ligation assays showed that HBx and SMYD3 co-localize predominantly in the cytoplasm. Luciferase reporter assay demonstrated that the interaction between HBx and SMYD3 activates activator protein 1 (AP-1) signaling, but not that of nuclear factor-kappa B (NF-kappa B). On the other hand, neither overexpression nor knockdown of SMYD3 altered production of HBV transcripts and HBV surface antigen (HBsAg). In conclusion, a novel HBx-interacting protein, SMYD3, was identified, leading to proposal of a novel mechanism of AP-1 activation in HBV-infected cells.
机译：乙型肝炎病毒（HBV）是一种广泛的人类病原体，通常会导致慢性肝炎，肝硬化和肝细胞癌。 HBV发病机理的详细机制仍知之甚少。 HBV X蛋白（HBx）是一种多功能调节剂，通过与多种宿主因子的相互作用来调节病毒复制和宿主细胞功能，例如细胞周期进程，细胞凋亡和蛋白质降解。最近，据报道丙型肝炎病毒的非结构蛋白5A（NS5A）与甲基转移酶SET和含MYND域的3（SMYD3）相互作用，这与染色质修饰和癌症的发展有关。由于HBx与NS5A共享有关病毒复制和发病机理的基本调控功能，因此决定检查HBx是否与SMYD3相互作用。在本研究中，通过免疫共沉淀分析证明，HBx与Huh-7.5细胞中异位表达和内源表达的SMYD3相互作用。缺失突变分析显示，HBx的C末端区域（氨基酸[aa] 131-154）和SMYD3的内部区域（aa 269-288）负责它们的相互作用。免疫荧光和邻近连接试验表明，HBx和SMYD3主要共定位在细胞质中。萤光素酶报告基因检测证明HBx和SMYD3之间的相互作用激活了激活蛋白1（AP-1）信号传导，但没有激活核因子-κB（NF-κB）信号传导。另一方面，SMYD3的过表达或敲低都不会改变HBV转录物和HBV表面抗原（HBsAg）的产生。总之，鉴定了一种新型的HBx相互作用蛋白SMYD3，从而提出了在HBV感染的细胞中激活AP-1的新机制。

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