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Elevated NTCP expression by an iPSC-derived human hepatocyte maintenance medium enhances HBV infection in NTCP-reconstituted HepG2 cells

BACKGROUND: The sodium taurocholate cotransporting polypeptide (NTCP) is a functional receptor for hepatitis B virus (HBV). NTCP-reconstituted human hepatoma cells support HBV infection, but the infection is suboptimal and no apparent HBV spread has been observed in this system. RESULTS: We found th...

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Autores principales: Li, Xinlei, Xu, Zhaohui, Mitra, Bidisha, Wang, Minghang, Guo, Haitao, Feng, Zongdi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256212/
https://www.ncbi.nlm.nih.gov/pubmed/34225786
http://dx.doi.org/10.1186/s13578-021-00641-1
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author Li, Xinlei
Xu, Zhaohui
Mitra, Bidisha
Wang, Minghang
Guo, Haitao
Feng, Zongdi
author_facet Li, Xinlei
Xu, Zhaohui
Mitra, Bidisha
Wang, Minghang
Guo, Haitao
Feng, Zongdi
author_sort Li, Xinlei
collection PubMed
description BACKGROUND: The sodium taurocholate cotransporting polypeptide (NTCP) is a functional receptor for hepatitis B virus (HBV). NTCP-reconstituted human hepatoma cells support HBV infection, but the infection is suboptimal and no apparent HBV spread has been observed in this system. RESULTS: We found that NTCP-reconstituted HepG2 cells were highly susceptible to HBV infection after cells were cultured in a commercial human inducible pluripotent stem cell (iPSC)-derived hepatocyte maintenance medium (HMM). The enhanced HBV infection coincided with increased NTCP expression, and was observed in six different clones of HepG2-NTCP cells. Promoter assays indicated that HMM activated the cytomegalovirus immediate-early (IE) promoter that drives the NTCP expression in the HepG2-NTCP cells. RNA-Seq analysis revealed that HMM upregulated multiple metabolic pathways. Despite highly upregulated NTCP expression by HMM, no obvious HBV spread was observed even in the presence of PEG 8000. CONCLUSIONS: Our data suggest that this particular medium could be used to enhance HBV infection in NTCP-reconstituted hepatocytes in vitro. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-021-00641-1.
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spelling pubmed-82562122021-07-06 Elevated NTCP expression by an iPSC-derived human hepatocyte maintenance medium enhances HBV infection in NTCP-reconstituted HepG2 cells Li, Xinlei Xu, Zhaohui Mitra, Bidisha Wang, Minghang Guo, Haitao Feng, Zongdi Cell Biosci Research BACKGROUND: The sodium taurocholate cotransporting polypeptide (NTCP) is a functional receptor for hepatitis B virus (HBV). NTCP-reconstituted human hepatoma cells support HBV infection, but the infection is suboptimal and no apparent HBV spread has been observed in this system. RESULTS: We found that NTCP-reconstituted HepG2 cells were highly susceptible to HBV infection after cells were cultured in a commercial human inducible pluripotent stem cell (iPSC)-derived hepatocyte maintenance medium (HMM). The enhanced HBV infection coincided with increased NTCP expression, and was observed in six different clones of HepG2-NTCP cells. Promoter assays indicated that HMM activated the cytomegalovirus immediate-early (IE) promoter that drives the NTCP expression in the HepG2-NTCP cells. RNA-Seq analysis revealed that HMM upregulated multiple metabolic pathways. Despite highly upregulated NTCP expression by HMM, no obvious HBV spread was observed even in the presence of PEG 8000. CONCLUSIONS: Our data suggest that this particular medium could be used to enhance HBV infection in NTCP-reconstituted hepatocytes in vitro. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-021-00641-1. BioMed Central 2021-07-05 /pmc/articles/PMC8256212/ /pubmed/34225786 http://dx.doi.org/10.1186/s13578-021-00641-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Li, Xinlei
Xu, Zhaohui
Mitra, Bidisha
Wang, Minghang
Guo, Haitao
Feng, Zongdi
Elevated NTCP expression by an iPSC-derived human hepatocyte maintenance medium enhances HBV infection in NTCP-reconstituted HepG2 cells
title Elevated NTCP expression by an iPSC-derived human hepatocyte maintenance medium enhances HBV infection in NTCP-reconstituted HepG2 cells
title_full Elevated NTCP expression by an iPSC-derived human hepatocyte maintenance medium enhances HBV infection in NTCP-reconstituted HepG2 cells
title_fullStr Elevated NTCP expression by an iPSC-derived human hepatocyte maintenance medium enhances HBV infection in NTCP-reconstituted HepG2 cells
title_full_unstemmed Elevated NTCP expression by an iPSC-derived human hepatocyte maintenance medium enhances HBV infection in NTCP-reconstituted HepG2 cells
title_short Elevated NTCP expression by an iPSC-derived human hepatocyte maintenance medium enhances HBV infection in NTCP-reconstituted HepG2 cells
title_sort elevated ntcp expression by an ipsc-derived human hepatocyte maintenance medium enhances hbv infection in ntcp-reconstituted hepg2 cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256212/
https://www.ncbi.nlm.nih.gov/pubmed/34225786
http://dx.doi.org/10.1186/s13578-021-00641-1
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