E-cadherin Plays a Role in Hepatitis B Virus Entry Through Affecting Glycosylated Sodium-Taurocholate Cotransporting Polypeptide Distribution
E-cadherin Plays a Role in Hepatitis B Virus Entry Through Affecting Glycosylated Sodium-Taurocholate Cotransporting Polypeptide Distribution
复制标题
E-钙粘蛋白通过影响糖基化牛磺胆酸钠共转运多肽分布在乙型肝炎病毒进入中发挥作用
DOI：
10.3389/fcimb.2020.00074
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发表时间：
2020-02-27
影响因子：
5.7
通讯作者：
Chen, Weixian
中科院分区：
文献类型：
--
作者：
Hu, Qin;Zhang, Feifei;Chen, Weixian
B型肝炎病毒（HBV）感染是慢性肝病和肝细胞癌的主要原因。目前的抗病毒治疗不能有效地根除HBV，需要进一步研究病毒感染的机制，以开发新的治疗药物。牛磺胆酸钠共转运多肽（NTCP）已被确定为HBV进入肝细胞的功能性受体。然而，NTCP受体不足以进入，其他膜蛋白有助于调节HBV进入。本研究旨在了解NTCP如何在HBV进入中发挥作用。在此，我们表明，敲低细胞-细胞粘附分子，E-钙粘蛋白显着减少感染的HBV颗粒和进入感染的肝细胞和细胞系的HBV假颗粒。糖基化NTCP通过与E-钙粘蛋白相互作用定位于质膜，这增加了与大HBV表面抗原的preS 1部分的相互作用。我们的研究提供了新的见解，在宿主细胞结合和病毒进入的水平上推进HBV感染的知识。
Hepatitis B virus (HBV) infection is a major cause of chronic liver disease and hepatocellular carcinoma. Current antiviral therapy does not effectively eradicate HBV and further investigations into the mechanisms of viral infection are needed to enable the development of new therapeutic agents. The sodium-taurocholate cotransporting polypeptide (NTCP) has been identified as a functional receptor for HBV entry in liver cells. However, the NTCP receptor is not sufficient for entry and other membrane proteins contribute to modulate HBV entry. This study seeks to understand how the NTCP functions in HBV entry. Herein we show that knockdown of the cell-cell adhesion molecule, E-cadherin significantly reduced infection by HBV particles and entry by HBV pseudoparticles in infected liver cells and cell lines. The glycosylated NTCP localizes to the plasma membrane through interaction with E- cadherin, which increases interaction with the preS1 portion of the Large HBV surface antigen. Our study contributes novel insights that advance knowledge of HBV infection at the level of host cell binding and viral entry.