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Published on: February 1, 2017
Elevated NTCP expression by an iPSC-derived human hepatocyte maintenance medium enhances HBV infection in
Xinlei Li1, Zhaohui Xu1, Bidisha Mitra2
1Center for Vaccines and Immunity, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, 43205, USA.
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.
