Hepatocyte polarization is essential for the productive entry of the hepatitis B

StephenW

Schulze, A., Mills, K., Weiss, T. S. and Urban, S. (2012), Hepatocyte polarization is essential for the productive entry of the hepatitis B virus. Hepatology, 55: 373–383. doi: 10.1002/hep.24707

Author Information

• 1Department of Infectious Diseases, Molecular Virology, Otto-Meyerhof-Zentrum, University Hospital Heidelberg, Heidelberg, Germany
  
• 2Food Standards Australia New Zealand, Canberra, Australia
  
• 3Department of Pediatrics and Adolescent Medicine, University Hospital Regensburg, Regensburg, Germany
  
  

• ‡These authors contributed equally to the work.
  
  
  
• §fax: +49-6221-56-1946
  
  
  
  

Email: Stephan Urban ([email protected])

*Department of Infectious Diseases, Molecular Virology, Otto-Meyerhof Zentrum, University Hospital Heidelberg, Im Neuenheimer Feld 350, 69120 Heidelberg, Germany

AbstractHuman hepatitis B virus (HBV) is characterized by a high species specificity and a distinct liver tropism. Within the liver, HBV replication occurs in differentiated and polarized hepatocytes. Accordingly, the in vitro HBV infection of primary human hepatocytes (PHHs) and the human hepatoma cell line, HepaRG, is restricted to differentiated, hepatocyte-like cells. Though preparations of PHH contain up to 100% hepatic cells, cultures of differentiated HepaRG cells are a mixture of hepatocyte-like and biliary-like epithelial cells. We used PHH and HepaRG cells and compared the influence of virus inoculation dose, cell differentiation, and polarization on productive HBV infection. At multiplicities of genome equivalents (mge) >8,000, almost 100% of PHHs could be infected. In contrast, only a subset of HepaRG cells stained positive for HBcAg at comparable or even higher mge. Infection predominantly occurred at the edges of islands of hepatocyte-like HepaRG cells. This indicates a limited accessibility of the HBV receptor, possibly as a result of its polar sorting. Multidrug resistance protein 2 (MRP2), a marker selectively transported to the apical (i.e., canalicular) cell membrane, revealed two polarization phenotypes of HepaRG cells. HBV infection within the islands of hepatocyte-like HepaRG cells preferentially occurred in cells that resemble PHH, exhibiting canalicular structures. However, disruption of cell-cell junctions allowed the additional infection of cells that do not display a PHH-like polarization. Conclusion: HBV enters hepatocytes via the basolateral membrane. This model, at least partially, explains the difference of PHH and HepaRG cells in infection efficacy, provides insights into natural HBV infection, and establishes a basis for optimization of the HepaRG infection system. (HEPATOLOGY 2012)








(6.合.彩)足球.篮球...各类投注开户下注

第一投注现金网:招代理年薪10万以上:yyu.cc

StephenW

摘要

人类B型肝炎病毒（HBV）的特点是高的种属特异性和独特的肝取向。肝脏内HBV的复制发生在分化和两极化的肝细胞。因此，在体外HBV感染原代人肝细胞（PHHs）和人肝癌细胞株，HepaRG，限制分化，肝细胞样细胞。尽管PHH的筹备工作，包含高达100％的肝细胞，分化HepaRG细胞培养的肝细胞样和胆汁样上皮细胞的混合物。我们用PHH和HepaRG细胞和病毒接种剂量，细胞分化，对生产的乙肝病毒感染的偏振的影响相比。在多重基因组当量（MGE）> 8,000，几乎100％的PHHs可能被感染。相比之下，只有一部分HepaRG细胞中HBcAg在同等或更高的MGE染色呈阳性。感染主要发生在岛屿肝HepaRG细胞的边缘。这表明有限的HBV受体辅助，可能作为一个其极地排序的结果。多药耐药相关蛋白2（MRP2的），选择性地运送到根尖（即小管）细胞膜标记，发现两个极化HepaRG细胞表型。优先发生在的岛屿，肝像HepaRG细胞内的乙肝病毒感染的细胞类似于PHH，参展毛细结构。然而，细胞与细胞交界处中断允许额外的不显示PHH类似极化的细胞感染。结论：乙肝病毒进入通过基底膜肝。这种模式，至少部分解释了天然HBV感染的PHH和HepaRG细胞在感染疗效的差异，提供了见解，并建立了优化HepaRG感染系统的基础。 （2012年肝病）

咬牙硬挺

感谢分享