title: Cellular uptake of hepatitis B virus envelope L particles is independent of sodium taurocholate cotransporting polypeptide, but dependent on heparan sulfate proteoglycan.
abstract: Sodium taurocholate cotransporting polypeptide (NTCP) was recently discovered as a hepatitis B virus (HBV) receptor, however, the detailed mechanism of HBV entry is not yet fully understood. We investigated the cellular entry pathway of HBV using recombinant HBV surface antigen L protein particles (bio-nanocapsules, BNCs). After the modification of L protein in BNCs with myristoyl group, myristoylated BNCs (Myr-BNCs) were found to bind to NTCP in vitro, and inhibit in vitro HBV infection competitively, suggesting that Myr-BNCs share NTCP-dependent infection machinery with HBV. Nevertheless, the cellular entry rates of Myr-BNCs and plasma-derived HBV surface antigen (HBsAg) particles were the same as those of BNCs in NTCP-overexpressing HepG2 cells. Moreover, the cellular entry of these particles was mainly driven by heparan sulfate proteoglycan-mediated endocytosis regardless of NTCP expression. Taken together, cell-surface NTCP may not be involved in the cellular uptake of HBV, while presumably intracellular NTCP plays a critical role.
authors.affiliation: The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan; Graduate School of Bioagricultural Sciences, Nagoya University, Aichi 464-8601, Japan; Japan Society for the Promotion of Science, Tokyo 102-0083, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Somiya
authors.affiliation: The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan; Graduate School of Bioagricultural Sciences, Nagoya University, Aichi 464-8601, Japan.
authors.forename: Qiushi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yoshimoto
authors.affiliation: The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Iijima
authors.affiliation: The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Tatematsu
authors.affiliation: The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nakai
authors.affiliation: The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Okajima
authors.affiliation: Central Research Resource Branch, Cancer Research Institute, Kanazawa University, Ishikawa 920-1192, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kuroki
authors.affiliation: Division of Virology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Ueda
authors.affiliation: The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan; Graduate School of Bioagricultural Sciences, Nagoya University, Aichi 464-8601, Japan. Electronic address: skuroda@sanken.osaka-u.ac.jp.
authors.forename: Shun'ichi
authors.initials: S
authors.lastname: Kuroda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004705:Endocytosis; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006509:Hepatitis B / Q000378:metabolism* / Q000821:virology*; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry; D029363:Organic Anion Transporters, Sodium-Dependent / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D027981:Symporters / Q000737:chemistry / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*; D053586:Virus Internalization; D057646:Virus Uncoating
chemical_list: D019812:Heparan Sulfate Proteoglycans; C096362:L protein, hepatitis B virus; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; D014759:Viral Envelope Proteins; C071908:sodium-bile acid cotransporter
keywords: Bio-nanocapsule; Endocytosis; Hepatitis B virus; Myristoylation; Virus uncoating