title: Association between hepatitis B virus and MHC class I polypeptide-related chain A in human hepatocytes derived from human-mouse chimeric mouse liver.
abstract: Due to the lack of efficient hepatitis B virus (HBV) infection systems, progress in understanding the role of innate immunity in HBV infection has remained challenging. Here we used human hepatocytes from a humanized severe combined immunodeficiency albumin promoter/enhancer driven-urokinase-type plasminogen activator mouse model for HBV infection. HBV DNA levels in culture medium from these human hepatocytes were 4.8-5.7 log IU/mL between day 16 and day 66 post-infection by HBV genotype C inoculum. HBV surface antigen (HBsAg) was also detected by chemiluminescent immunoassay from day 7 to day 66 post-infection. Western blot analysis revealed that major histocompatibility complex class I-related chain A (MICA), which plays a role in the innate immune system, was induced in HBV-infected human hepatocytes 27 days after infection compared with the uninfected control. MICA was reduced at day 62 and undetectable at day 90. Of interest, MICA expression by human hepatocytes increased after HBV infection and decreased before HBsAg loss. Human hepatocytes derived from chimeric mice with hepatocyte-humanized liver could support HBV genome replication. Further studies of the association between HBV replication and MICA induction should be conducted.
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Reina
authors.initials: R
authors.lastname: Sasaki
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. Electronic address: kandat-cib@umin.ac.jp.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan; Department of Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakamoto
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Haga
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Xia
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shirasawa
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002678:Chimera / Q000276:immunology / Q000821:virology; D006509:Hepatitis B / Q000276:immunology* / Q000821:virology*; D006515:Hepatitis B virus / Q000302:isolation & purification / Q000502:physiology*; D022781:Hepatocytes / Q000276:immunology* / Q000821:virology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000821:virology; D051379:Mice; D016513:Mice, SCID
chemical_list: D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A
keywords: HBV; Hepatocyte; Innate immunity; MICA; NKG2D ligand