title: Core-fucosylation plays a pivotal role in hepatitis B pseudo virus infection: a possible implication for HBV glycotherapy.
abstract: The functions of cell surface proteins, such as growth factor receptors and virus/bacteria-entry receptors, can be dynamically regulated by oligosaccharide modifications. In the present study, we investigated the involvement of glycosylation in hepatitis B virus (HBV) entry into hepatoma cells. Infection of oligosaccharide-remodeling hepatoma cells with a pseudo virus of HBV, bio-nanocapsule (BNC), was evaluated by flow cytometry and confocal microscopy. Among various experiments using several hepatoma cells, marked difference was observed between Huh6 cells and HB611 cells, which were established by HBV gene transfection into hepatoma cells. Comprehensive oligosaccharide analysis showed dramatic increases of core fucosylation in HB611 cells, compared with Huh6 cells. Knock down of fucosyltransferase 8 (FUT8) reduced BNC entry into HB611 cells. In contrast, overexpression of FUT8 in Huh6 cells increased BNC entry. Although expression of sodium taurocholate cotransporting polypeptide (NTCP), which is one of HBV receptors was very similar between Huh6 and HB611 cells, proteins coprecipitated with NTCP were dependent on levels of core-fucosylation, suggesting that core-fucosylation regulates BNC entry into hepatoma cells. Our findings demonstrate that core-fucosylation is an important glycosylation for HBV infection of hepatoma cells through HBV-receptor-mediated endocytosis. Down-regulation of core-fucosylation may be a novel target for HBV therapy.
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka.
authors.forename: Shinji
authors.initials: S
authors.lastname: Takamatsu
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka.
authors.forename: Mayuka
authors.initials: M
authors.lastname: Shimomura
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka.|Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kamada
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka.
authors.forename: Haruka
authors.initials: H
authors.lastname: Maeda
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Sobajima
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Hikita
authors.affiliation: The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihoga-oka Ibaraki, 567-0047, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Iijima
authors.affiliation: Applied Microbiology Laboratory, International Center for Biotechnology, Osaka University, 2-1 Yamada-oka, Suita 565-0871, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Okamoto
authors.affiliation: Applied Microbiology Laboratory, International Center for Biotechnology, Osaka University, 2-1 Yamada-oka, Suita 565-0871, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Misaki
authors.affiliation: Applied Microbiology Laboratory, International Center for Biotechnology, Osaka University, 2-1 Yamada-oka, Suita 565-0871, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Fujiyama
authors.affiliation: Department of Bio-system Pharmacology, Osaka University Graduate School of Medicine.
authors.forename: Shushi
authors.initials: S
authors.lastname: Nagamori
authors.affiliation: Department of Bio-system Pharmacology, Osaka University Graduate School of Medicine.
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Kanai
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
authors.affiliation: Department of Microbiology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Ueda
authors.affiliation: The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihoga-oka Ibaraki, 567-0047, Japan.
authors.forename: Shun'ichi
authors.initials: S
authors.lastname: Kuroda
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka emiyoshi@sahs.med.osaka-u.ac.jp.
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
mesh_terms: D005643:Fucose / Q000378:metabolism*; D006031:Glycosylation; D006509:Hepatitis B / Q000378:metabolism*; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053769:Nanocapsules / Q000737:chemistry; D014407:Tumor Cells, Cultured
chemical_list: D053769:Nanocapsules; D005643:Fucose
keywords: HBV; NTCP; core fucose; endocytosis; glycosylation