title: HBV life cycle is restricted in mouse hepatocytes expressing human NTCP.
abstract: Recent studies have revealed that human sodium taurocholate cotransporting polypeptide (SLC10A1 or NTCP) is a functional cellular receptor for hepatitis B virus (HBV). However, whether human NTCP can support HBV infection in mouse hepatocyte cell lines has not been clarified. Because an HBV-permissible mouse model would be helpful for the study of HBV pathogenesis, it is necessary to investigate whether human NTCP supports the susceptibility of mouse hepatocyte cell lines to HBV. The results show that exogenous human NTCP expression can render non-susceptible HepG2 (human), Huh7 (human), Hepa1-6 (mouse), AML-12 (mouse) cell lines and primary mouse hepatocyte (PMH) cells susceptible to hepatitis D virus (HDV) which employs HBV envelope proteins. However, human NTCP could only introduce HBV susceptibility in human-derived HepG2 and Huh7 cells, but not in mouse-derived Hepa1-6, AML-12 or PMH cells. These data suggest that although human NTCP is a functional receptor that mediates HBV infection in human cells, it cannot support HBV infection in mouse hepatocytes. Our study indicated that the restriction of HBV in mouse hepatocytes likely occurs after viral entry but prior to viral transcription. We have excluded the role of mouse hepatocyte nuclear factors in the restriction of the HBV life cycle and showed that knockdown or inhibition of Sting, TBK1, IRF3 or IRF7, the components of the anti-viral signaling pathways, had no effect on HBV infection in mouse hepatocytes. Therefore, murine restriction factors that limit HBV infection need to be identified before a HBV-permissible mouse line can be created.
authors: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, and School of Life Sciences, Xiamen University, Xiamen 361005, China.
authors: Hanjie
authors: H
authors: Li
authors: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, and School of Life Sciences, Xiamen University, Xiamen 361005, China.
authors: Qiuyu
authors: Q
authors: Zhuang
authors: 1] State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, and School of Life Sciences, Xiamen University, Xiamen 361005, China [2] School of Chemical Engineering, Huaqiao University, Xiamen 361005, China.
authors: Yuze
authors: Y
authors: Wang
authors: National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen 361005, China.
authors: Tianying
authors: T
authors: Zhang
authors: National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen 361005, China.
authors: Jinghua
authors: J
authors: Zhao
authors: National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen 361005, China.
authors: Yali
authors: Y
authors: Zhang
authors: National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen 361005, China.
authors: Junfang
authors: J
authors: Zhang
authors: School of Chemical Engineering, Huaqiao University, Xiamen 361005, China.
authors: Yi
authors: Y
authors: Lin
authors: National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen 361005, China.
authors: Quan
authors: Q
authors: Yuan
authors: National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen 361005, China.
authors: Ningshao
authors: N
authors: Xia
authors: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, and School of Life Sciences, Xiamen University, Xiamen 361005, China.
authors: Jiahuai
authors: J
authors: Han
mesh_terms: D000818:Animals; D004198:Disease Susceptibility; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000276:immunology* / Q000635:transmission; D006515:Hepatitis B virus / Q000502:physiology*; D003699:Hepatitis D / Q000276:immunology* / Q000635:transmission; D003698:Hepatitis Delta Virus / Q000502:physiology*; D022781:Hepatocytes / Q000276:immunology / Q000821:virology*; D058507:Host Specificity / Q000235:genetics; D006801:Humans; D051379:Mice; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D019076:Transgenes / Q000235:genetics; D018406:Virus Physiological Phenomena
chemical_list: D029363:Organic Anion Transporters, Sodium-Dependent; D034741:RNA, Small Interfering; D011991:Receptors, Virus; D027981:Symporters; D014157:Transcription Factors; C071908:sodium-bile acid cotransporter