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Modulation of hepatitis B virus infection by epidermal growth factor secreted from liver sinusoidal endothelial cells
Hepatocytes derived from human iPSCs are useful to study hepatitis B virus (HBV) infection, however infection efficiency is rather poor. In order to improve the efficiency of HBV infection to iPSC-derived hepatocytes, we set a co-culture of hepatocytes with liver non-parenchymal cells and found that...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462976/ https://www.ncbi.nlm.nih.gov/pubmed/32873852 http://dx.doi.org/10.1038/s41598-020-71453-5 |
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author | Chen, Shin-Wei Himeno, Misao Koui, Yuta Sugiyama, Masaya Nishitsuji, Hironori Mizokami, Masashi Shimotohno, Kunitada Miyajima, Atsushi Kido, Taketomo |
author_facet | Chen, Shin-Wei Himeno, Misao Koui, Yuta Sugiyama, Masaya Nishitsuji, Hironori Mizokami, Masashi Shimotohno, Kunitada Miyajima, Atsushi Kido, Taketomo |
author_sort | Chen, Shin-Wei |
collection | PubMed |
description | Hepatocytes derived from human iPSCs are useful to study hepatitis B virus (HBV) infection, however infection efficiency is rather poor. In order to improve the efficiency of HBV infection to iPSC-derived hepatocytes, we set a co-culture of hepatocytes with liver non-parenchymal cells and found that liver sinusoidal endothelial cells (LSECs) enhanced HBV infection by secreting epidermal growth factor (EGF). While EGF receptor (EGFR) is known as a co-receptor for HBV, we found that EGF enhanced HBV infection at a low dose of EGF, whereas EGF at a high dose suppressed HBV infection. EGFR is internalized by clathrin-mediated endocytosis (CME) and clathrin-independent endocytosis (CIE) pathways depending on the dose of EGF. At a high dose of EGF, the endocytosed EGFR via CIE is degraded in the lysosome. This study is the first to provide evidence that HBV is endocytosed via CME and CIE pathways at a low and high dose of EGF, respectively. In conclusion, we developed an in vitro system of HBV infection using iPSC-derived liver cells, and show that EGF secreted from LSECs modulates HBV infection in a dose dependent manner. |
format | Online Article Text |
id | pubmed-7462976 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-74629762020-09-03 Modulation of hepatitis B virus infection by epidermal growth factor secreted from liver sinusoidal endothelial cells Chen, Shin-Wei Himeno, Misao Koui, Yuta Sugiyama, Masaya Nishitsuji, Hironori Mizokami, Masashi Shimotohno, Kunitada Miyajima, Atsushi Kido, Taketomo Sci Rep Article Hepatocytes derived from human iPSCs are useful to study hepatitis B virus (HBV) infection, however infection efficiency is rather poor. In order to improve the efficiency of HBV infection to iPSC-derived hepatocytes, we set a co-culture of hepatocytes with liver non-parenchymal cells and found that liver sinusoidal endothelial cells (LSECs) enhanced HBV infection by secreting epidermal growth factor (EGF). While EGF receptor (EGFR) is known as a co-receptor for HBV, we found that EGF enhanced HBV infection at a low dose of EGF, whereas EGF at a high dose suppressed HBV infection. EGFR is internalized by clathrin-mediated endocytosis (CME) and clathrin-independent endocytosis (CIE) pathways depending on the dose of EGF. At a high dose of EGF, the endocytosed EGFR via CIE is degraded in the lysosome. This study is the first to provide evidence that HBV is endocytosed via CME and CIE pathways at a low and high dose of EGF, respectively. In conclusion, we developed an in vitro system of HBV infection using iPSC-derived liver cells, and show that EGF secreted from LSECs modulates HBV infection in a dose dependent manner. Nature Publishing Group UK 2020-09-01 /pmc/articles/PMC7462976/ /pubmed/32873852 http://dx.doi.org/10.1038/s41598-020-71453-5 Text en © The Author(s) 2020 Open Access This 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/. |
spellingShingle | Article Chen, Shin-Wei Himeno, Misao Koui, Yuta Sugiyama, Masaya Nishitsuji, Hironori Mizokami, Masashi Shimotohno, Kunitada Miyajima, Atsushi Kido, Taketomo Modulation of hepatitis B virus infection by epidermal growth factor secreted from liver sinusoidal endothelial cells |
title | Modulation of hepatitis B virus infection by epidermal growth factor secreted from liver sinusoidal endothelial cells |
title_full | Modulation of hepatitis B virus infection by epidermal growth factor secreted from liver sinusoidal endothelial cells |
title_fullStr | Modulation of hepatitis B virus infection by epidermal growth factor secreted from liver sinusoidal endothelial cells |
title_full_unstemmed | Modulation of hepatitis B virus infection by epidermal growth factor secreted from liver sinusoidal endothelial cells |
title_short | Modulation of hepatitis B virus infection by epidermal growth factor secreted from liver sinusoidal endothelial cells |
title_sort | modulation of hepatitis b virus infection by epidermal growth factor secreted from liver sinusoidal endothelial cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462976/ https://www.ncbi.nlm.nih.gov/pubmed/32873852 http://dx.doi.org/10.1038/s41598-020-71453-5 |
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