title: Elucidation of the early infection machinery of hepatitis B virus by using bio-nanocapsule.
abstract: Currently, hepatitis B virus (HBV), upon attaching to human hepatocytes, is considered to interact first with heparan sulfate proteoglycan (HSPG)viaan antigenic loop of HBV envelope S protein. Then, it is promptly transferred to the sodium taurocholate cotransporting polypeptide (NTCP)viathe myristoylated N-terminal sequence of pre-S1 region (from Gly-2 to Gly-48, HBV genotype D), and it finally enters the cell by endocytosis. However, it is not clear how HSPG passes HBV to NTCP and how NTCP contributes to the cellular entry of HBV. Owing to the poor availability and the difficulty of manipulations, including fluorophore encapsulation, it has been nearly impossible to perform biochemical and cytochemical analyses using a substantial amount of HBV. A bio-nanocapsule (BNC), which is a hollow nanoparticle consisting of HBV envelope L protein, was efficiently synthesized inSaccharomyces cerevisiae. Since BNC could encapsulate payloads (drugs, genes, proteins) and specifically enter human hepatic cells utilizing HBV-derived infection machinery, it could be used as a model of HBV infection to elucidate the early infection machinery. Recently, it was demonstrated that the N-terminal sequence of pre-S1 region (from Asn-9 to Gly-24) possesses low pH-dependent fusogenic activity, which might play a crucial role in the endosomal escape of BNC payloads and in the uncoating process of HBV. In this minireview, we describe a model in which each domain of the HBV L protein contributes to attachment onto human hepatic cells through HSPG, initiation of endocytosis, interaction with NTCP in endosomes, and consequent provocation of membrane fusion followed by endosomal escape.
authors: Qiushi Liu, Masaharu Somiya, Shun'ichi Kuroda, Department of Biomolecular Science and Reaction, The Institute of Scientific and Industrial Research, Osaka University, Ibaraki 567-0047, Japan.
authors: Qiushi
authors: Q
authors: Liu
authors: Qiushi Liu, Masaharu Somiya, Shun'ichi Kuroda, Department of Biomolecular Science and Reaction, The Institute of Scientific and Industrial Research, Osaka University, Ibaraki 567-0047, Japan.
authors: Masaharu
authors: M
authors: Somiya
authors: Qiushi Liu, Masaharu Somiya, Shun'ichi Kuroda, Department of Biomolecular Science and Reaction, The Institute of Scientific and Industrial Research, Osaka University, Ibaraki 567-0047, Japan.
authors: Shun'ichi
authors: S
authors: Kuroda
mesh_terms: D000818:Animals; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D006509:Hepatitis B / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008561:Membrane Fusion; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry*; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism; D000072417:Protein Domains; D027981:Symporters / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics*
chemical_list: D053769:Nanocapsules; D029363:Organic Anion Transporters, Sodium-Dependent; C118669:S envelope protein, hepatitis B virus; D027981:Symporters; D014759:Viral Envelope Proteins; C071908:sodium-bile acid cotransporter
keywords: Bio-nanocapsule; Endosomal escape; Heparan sulfate proteoglycan; Hepatitis B virus; Sodium taurocholate cotransporting polypeptide