Modulation of hepatitis B virus infection by epidermal growth factor secreted from liver sinusoidal endothelial cells

Shin Wei Chen, Misao Himeno, Yuta Koui, Masaya Sugiyama, Hironori Nishitsuji, Masashi Mizokami, Kunitada Shimotohno, Atsushi Miyajima, Taketomo Kido

研究成果: Article査読

4 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号14349
ジャーナルScientific reports
10
1
DOI
出版ステータスPublished - 01-12-2020
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All Science Journal Classification (ASJC) codes

  • 一般

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