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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Fuminori Sakurai, Seiji Mitani, Tatsuro Yamamoto, Kazuo Takayama, Masashi Tachibana, Koichi Watashi, Takaji Wakita, Sayuki Iijima, Yasuhito Tanaka, Hiroyuki Mizuguchi

ABSTRACT

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. More... »

PAGES

45698

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep45698

DOI

http://dx.doi.org/10.1038/srep45698

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1084511358

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28374759


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