人干细胞衍生的肝细胞作为乙型肝炎病毒感染，传播和病毒 -

StephenW

Human stem cell-derived hepatocytes as a model for hepatitis B virus infection, spreading and virus-host interactions
Yuchen Xia
, Arnaud Carpentier
, Xiaoming Cheng
, Peter Daniel Block
, Yao Zhao
, Zhensheng Zhang
, Ulrike Protzer
, T. Jake Liang'Correspondence information about the author T. Jake LiangEmail the author T. Jake Liang
See Editorial, pages 473–475
Article has an altmetric score of 3
DOI: http://dx.doi.org/10.1016/j.jhep.2016.10.009 |

Background & Aims

One major obstacle of hepatitis B virus (HBV) research is the lack of efficient cell culture system permissive for viral infection and replication. The aim of our study was to establish a robust HBV infection model by using hepatocyte-like cells (HLCs) derived from human pluripotent stem cells.
Methods

HLCs were differentiated from human embryonic stem cells and induced pluripotent stem cells. Maturation of hepatocyte functions was determined. After HBV infection, total viral DNA, cccDNA, total viral RNA, pgRNA, HBeAg and HBsAg were measured.
Results

More than 90% of the HLCs expressed strong signals of human hepatocyte markers, like albumin, as well as known host factors required for HBV infection, suggesting that these cells possessed key features of mature hepatocytes. Notably, HLCs expressed the viral receptor sodium-taurocholate cotransporting polypeptide more stably than primary human hepatocytes (PHHs). HLCs supported robust infection and some spreading of HBV. Finally, by using this model, we identified two host-targeting agents, genistin and PA452, as novel antivirals.
Conclusions

Stem cell-derived HLCs fully support HBV infection. This novel HLC HBV infection model offers a unique opportunity to advance our understanding of the molecular details of the HBV life cycle; to further characterize virus-host interactions and to define new targets for HBV curative treatment.
Lay summary

Our study used human pluripotent stem cells to develop hepatocyte-like cells (HLCs) capable of expressing hepatocyte markers and host factors important for HBV infection. These cells fully support HBV infection and virus-host interactions, allowing for the identification of two novel antiviral agents. Thus, stem cell-derived HLCs provide a highly physiologically relevant system to advance our understanding of viral life cycle and provide a new tool for antiviral drug screening and development.
Keywords:
Hepatitis B virus, Stem cell, Model, Antivirals, Antiviral agents, Hepatocytes, DNA, Viral

StephenW

人干细胞衍生的肝细胞作为乙型肝炎病毒感染，传播和病毒 - 宿主相互作用的模型
刘玉成
，Arnaud Carpentier
，Xiaoming Cheng
，彼得·丹尼尔块
，赵耀
，张振生
，Ulrike Protzer
，T. Jake Liang通讯作者：李杰良电子邮件作者T. Jake Liang
见编辑，第473-475页
文章的得分为3
DOI：http://dx.doi.org/10.1016/j.jhep.2016.10.009 |
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背景和目的

（HB）衍生自有效的细胞培养系统，使用源自人多能干细胞的肝细胞样细胞（HLC）。
方法

从人胚胎干细胞和诱导多能干细胞分化Hector。确定肝细胞功能的成熟。 HBV感染后，测量总病毒DNA，cccDNA，总病毒RNA，pgRNA，HBeAg和HBsAg。
结果

超过90％的HLCs表达人肝细胞标记物，如白蛋白的强信号，以及HBV感染所需的已知宿主因子，表明这些细胞具有成熟肝细胞的关键特征。值得注意的是，HLCs比原代人肝细胞（PHH）更稳定地表达病毒受体牛磺胆酸钠转运多肽。 HLC支持强大的感染和HBV的一些传播。最后，通过使用这种模型，我们确定了两种主机靶向剂，染料木苷和PA452，作为新型抗病毒剂。
结论

干细胞衍生的HLCs完全支持HBV感染。这种新型HLC HBV感染模型提供了一个独特的机会，提高我们对HBV生命周期的分子细节的理解;以进一步表征病毒 - 宿主的相互作用并定义HBV治疗性治疗的新靶标
放置摘要

我们的细胞像HBV免疫和宿主相互作用，批准用于鉴定能够表达肝细胞标记物和对HBV感染重要的宿主因子的两种新型抗病毒剂（HLC）。 。因此，干细胞衍生的HLC提供了高度生理相关的系统，以提高我们对病毒生命周期的了解，并为抗病毒药物筛选和开发提供了一个新的工具。
关键词：
乙型肝炎病毒，干细胞，模型，抗病毒剂，抗病毒剂，肝细胞，DNA，病毒

StephenW

Stem cell-derived hepatocytes: A promising novel tool to study hepatitis B virus infection
Yi Ni
, Stephan Urban'Correspondence information about the author Stephan UrbanEmail the author Stephan Urban
Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Im Neuenheimer Feld 345, D-69120 Heidelberg, Germany
German Center of Infectious Diseases (DZIF), Heidelberg, Germany

http://www.journal-of-hepatology ... seases%7CHepatology

MP4

Stephan Urban