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) via an antigenic loop of HBV envelope S protein. Then, it is promptly transferred to the sodium taurocholate cotransporting polypeptide (NTCP) via the 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 in Saccharomyces 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.

Binding of Nanoparticles Harboring Recombinant Large Surface Protein of Hepatitis B Virus to Scavenger Receptor Class B Type 1

“…BNCs (i.e., we used emBNCs in this study) were prepared as reported previously [ 6 ]. Briefly, an expression plasmid, which was constructed by introducing two mutations (Q129R and G145R) in wild-type BNC expression plasmid (pGLDLIIP39-RcT), was transfected into S. cerevisiae AH22R − .…”

“…They are expected to be safer carriers than wild-type BNCs for in vivo use [ 5 ]. Although BNCs were once expected as a model mimicking HBsAg or HBV particles, the usefulness of BNCs as an HBV model is thought to be limited [ 6 ].…”

Peptides to combat viral infectious diseases

“…The host receptor, HSPG binds to pre-S1 to initiate the viral integration to host cells. This is followed by the interaction between HBV and the high-affinity receptor NTCP for endocytosis [ 127 , 84 ]. Liu and colleagues designed an array of pre-S1 truncations displayed on liposomes (LPs).…”

Viral mechanisms for docking and delivering at nuclear pore complexes

“…HBV first binds HPSG and then the pre-S1 domain of envelope protein L interacts with the liver bile transporter, NTCP [222][223][224].…”