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Human induced-pluripotent stem cell-derived hepatocyte-like cells as an in vitro model of human hepatitis B virus infection.
- Source :
-
Scientific reports [Sci Rep] 2017 Apr 04; Vol. 7, pp. 45698. Date of Electronic Publication: 2017 Apr 04. - Publication Year :
- 2017
-
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.
- Subjects :
- Cell Differentiation physiology
Cell Line
Hep G2 Cells
Hepatitis B genetics
Hepatitis B metabolism
Hepatitis B virus genetics
Hepatocytes metabolism
Host-Pathogen Interactions physiology
Humans
Induced Pluripotent Stem Cells metabolism
Organic Anion Transporters, Sodium-Dependent genetics
Organic Anion Transporters, Sodium-Dependent metabolism
RNA, Viral genetics
Symporters genetics
Symporters metabolism
Viral Proteins genetics
Viral Proteins metabolism
Hepatitis B pathology
Hepatitis B virology
Hepatocytes cytology
Hepatocytes virology
Induced Pluripotent Stem Cells cytology
Induced Pluripotent Stem Cells virology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 7
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 28374759
- Full Text :
- https://doi.org/10.1038/srep45698