Xinlei Li1, Zhaohui Xu1, Bidisha Mitra2, Minghang Wang1, Haitao Guo2, Zongdi Feng3,4. 1. Center for Vaccines and Immunity, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, 43205, USA. 2. Department of Microbiology and Molecular Genetics and UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA. 3. Center for Vaccines and Immunity, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, 43205, USA. Zongdi.feng@nationwidechildrens.org. 4. Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA. Zongdi.feng@nationwidechildrens.org.
Abstract
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.
BACKGROUND: The sodium taurocholate cotransporting polypeptide (NTCP) is a functional receptor for hepatitis B virus (HBV). NTCP-reconstituted humanhepatoma 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.
Entities:
Keywords:
CMV promoter; Entry; Hepatitis B virus; NTCP
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