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Human induced-pluripotent stem cell-derived hepatocyte-like cells as an in vitro model of human hepatitis B virus infection

In order to understand the life cycle of hepatitis B virus (HBV) and to develop efficient anti-HBV drugs, a useful in vitro cell culture system which allows HBV infection and recapitulates virus-host interactions is essential; however, pre-existing in vitro HBV infection models are often problematic...

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Autores principales: Sakurai, Fuminori, Mitani, Seiji, Yamamoto, Tatsuro, Takayama, Kazuo, Tachibana, Masashi, Watashi, Koichi, Wakita, Takaji, Iijima, Sayuki, Tanaka, Yasuhito, Mizuguchi, Hiroyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379564/
https://www.ncbi.nlm.nih.gov/pubmed/28374759
http://dx.doi.org/10.1038/srep45698
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author Sakurai, Fuminori
Mitani, Seiji
Yamamoto, Tatsuro
Takayama, Kazuo
Tachibana, Masashi
Watashi, Koichi
Wakita, Takaji
Iijima, Sayuki
Tanaka, Yasuhito
Mizuguchi, Hiroyuki
author_facet Sakurai, Fuminori
Mitani, Seiji
Yamamoto, Tatsuro
Takayama, Kazuo
Tachibana, Masashi
Watashi, Koichi
Wakita, Takaji
Iijima, Sayuki
Tanaka, Yasuhito
Mizuguchi, Hiroyuki
author_sort Sakurai, Fuminori
collection PubMed
description In order to understand the life cycle of hepatitis B virus (HBV) and to develop efficient anti-HBV drugs, a useful in vitro cell culture system which allows HBV infection and recapitulates virus-host interactions is essential; however, pre-existing in vitro HBV infection models are often problematic. Here, we examined the potential of human induced-pluripotent stem (iPS) cell-derived hepatocyte-like cells (iPS-HLCs) as an in vitro HBV infection model. Expression levels of several genes involved in HBV infection, including the sodium taurocholate cotransporting polypeptide (NTCP) gene, were gradually elevated as the differentiation status of human iPS cells proceeded to iPS-HLCs. The mRNA levels of these genes were comparable between primary human hepatocytes (PHHs) and iPS-HLCs. Following inoculation with HBV, we found significant production of HBV proteins and viral RNAs in iPS-HLCs. The three major forms of the HBV genome were detected in iPS-HLCs by Southern blotting analysis. Anti-HBV agents entecavir and Myrcludex-B, which are a nucleoside analogue reverse transcriptase inhibitor and a synthetic pre-S1 peptide, respectively, significantly inhibited HBV infection in iPS-HLCs. These data demonstrate that iPS-HLCs can be used as a promising in vitro HBV infection model.
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spelling pubmed-53795642017-04-07 Human induced-pluripotent stem cell-derived hepatocyte-like cells as an in vitro model of human hepatitis B virus infection Sakurai, Fuminori Mitani, Seiji Yamamoto, Tatsuro Takayama, Kazuo Tachibana, Masashi Watashi, Koichi Wakita, Takaji Iijima, Sayuki Tanaka, Yasuhito Mizuguchi, Hiroyuki Sci Rep Article In order to understand the life cycle of hepatitis B virus (HBV) and to develop efficient anti-HBV drugs, a useful in vitro cell culture system which allows HBV infection and recapitulates virus-host interactions is essential; however, pre-existing in vitro HBV infection models are often problematic. Here, we examined the potential of human induced-pluripotent stem (iPS) cell-derived hepatocyte-like cells (iPS-HLCs) as an in vitro HBV infection model. Expression levels of several genes involved in HBV infection, including the sodium taurocholate cotransporting polypeptide (NTCP) gene, were gradually elevated as the differentiation status of human iPS cells proceeded to iPS-HLCs. The mRNA levels of these genes were comparable between primary human hepatocytes (PHHs) and iPS-HLCs. Following inoculation with HBV, we found significant production of HBV proteins and viral RNAs in iPS-HLCs. The three major forms of the HBV genome were detected in iPS-HLCs by Southern blotting analysis. Anti-HBV agents entecavir and Myrcludex-B, which are a nucleoside analogue reverse transcriptase inhibitor and a synthetic pre-S1 peptide, respectively, significantly inhibited HBV infection in iPS-HLCs. These data demonstrate that iPS-HLCs can be used as a promising in vitro HBV infection model. Nature Publishing Group 2017-04-04 /pmc/articles/PMC5379564/ /pubmed/28374759 http://dx.doi.org/10.1038/srep45698 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Sakurai, Fuminori
Mitani, Seiji
Yamamoto, Tatsuro
Takayama, Kazuo
Tachibana, Masashi
Watashi, Koichi
Wakita, Takaji
Iijima, Sayuki
Tanaka, Yasuhito
Mizuguchi, Hiroyuki
Human induced-pluripotent stem cell-derived hepatocyte-like cells as an in vitro model of human hepatitis B virus infection
title Human induced-pluripotent stem cell-derived hepatocyte-like cells as an in vitro model of human hepatitis B virus infection
title_full Human induced-pluripotent stem cell-derived hepatocyte-like cells as an in vitro model of human hepatitis B virus infection
title_fullStr Human induced-pluripotent stem cell-derived hepatocyte-like cells as an in vitro model of human hepatitis B virus infection
title_full_unstemmed Human induced-pluripotent stem cell-derived hepatocyte-like cells as an in vitro model of human hepatitis B virus infection
title_short Human induced-pluripotent stem cell-derived hepatocyte-like cells as an in vitro model of human hepatitis B virus infection
title_sort human induced-pluripotent stem cell-derived hepatocyte-like cells as an in vitro model of human hepatitis b virus infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379564/
https://www.ncbi.nlm.nih.gov/pubmed/28374759
http://dx.doi.org/10.1038/srep45698
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