Special Issue "Hepatitis B Virus: Its Life Cycle and the Therapeutic Targets"

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: 30 November 2021.

Special Issue Editor

Prof. Dr. Keiji Ueda
E-Mail Website
Guest Editor
Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine.2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
Interests: Virus; Receptor; Gene Regulation; Replication; Virus-Host Interaction; Latent Infection; Lytic Infection; Virus engineering

Special Issue Information

Dear Colleagues,

We do not have many or good options to the save lives of HBV-infected people around the world. Finding NTCP (sodium taurocholate co-transporting peptide) has enabled us to analyze the HBV life cycle in vitro using human hepatoma cell lines, though it may not be enough. Much knowledge of the HBV life cycle has been accumulating, and thus it is time to think of the next generation of HBV therapy.

This Special Issue will accept all kinds of manuscripts (reviews, research articles, and short communications). Based on the HBV life cycle, what kind of therapy will be designed? What factors could be targets for HBV treatment? Conceptual ideas on HBV treatment and analyses on new compounds to act on cellular targets are also of interest. We would like to discuss the future of HBV treatment, with a view to conquering the infection.

Prof. Dr. Keiji Ueda
Guest Editor

Manuscript Submission Information

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Keywords

  • Hepatitis B virus (HBV)
  • HBV infection system in vitro
  • Viral life cycle
  • Host and virus interaction
  • cccDNA

Published Papers (4 papers)

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Research

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Article
Binding of Nanoparticles Harboring Recombinant Large Surface Protein of Hepatitis B Virus to Scavenger Receptor Class B Type 1
Viruses 2021, 13(7), 1334; https://doi.org/10.3390/v13071334 - 10 Jul 2021
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Abstract
(1) Background: As nanoparticles containing the hepatitis B virus (HBV) large (L) surface protein produced in yeast are expected to be useful as a carrier for targeting hepatocytes, they are also referred to as bio-nanocapsules (BNCs). However, a definitive cell membrane receptor for [...] Read more.
(1) Background: As nanoparticles containing the hepatitis B virus (HBV) large (L) surface protein produced in yeast are expected to be useful as a carrier for targeting hepatocytes, they are also referred to as bio-nanocapsules (BNCs). However, a definitive cell membrane receptor for BNC binding has not yet been identified. (2) Methods: By utilizing fluorescence-labeled BNCs, we examined BNC binding to the scavenger receptor class B type 1 (SR-B1) expressed in HEK293T cells. (3) Results: Analyses employing SR-B1 siRNA and expression of SR-B1 fused with a green fluorescent protein (SR-B1-GFP) indicated that BNCs bind to SR-B1. As mutagenesis induced in the SR-B1 extracellular domain abrogates or attenuates BNC binding and endocytosis via SR-B1 in HEK293T cells, it was suggested that the ligand-binding site of SR-B1 is similar or close among high-density lipoprotein (HDL), silica, liposomes, and BNCs. On the other hand, L protein was suggested to attenuate an interaction between phospholipids and SR-B1. (4) Conclusions: SR-B1 can function as a receptor for binding and endocytosis of BNCs in HEK293T cells. Being expressed various types of cells, it is suggested that functions as a receptor for BNCs not only in HEK293T cells but also in other types of cells. Full article
(This article belongs to the Special Issue Hepatitis B Virus: Its Life Cycle and the Therapeutic Targets)
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Article
HBV Pre-S1-Derived Myristoylated Peptide (Myr47): Identification of the Inhibitory Activity on the Cellular Uptake of Lipid Nanoparticles
Viruses 2021, 13(5), 929; https://doi.org/10.3390/v13050929 - 17 May 2021
Cited by 2 | Viewed by 787
Abstract
The Myr47 lipopeptide, consisting of hepatitis B virus (HBV) pre-S1 domain (myristoylated 2–48 peptide), is an effective commercialized anti-HBV drug that prevents the interaction of HBV with sodium taurocholate cotransporting polypeptide (NTCP) on human hepatocytes, an activity which requires both N-myristoylation residue and [...] Read more.
The Myr47 lipopeptide, consisting of hepatitis B virus (HBV) pre-S1 domain (myristoylated 2–48 peptide), is an effective commercialized anti-HBV drug that prevents the interaction of HBV with sodium taurocholate cotransporting polypeptide (NTCP) on human hepatocytes, an activity which requires both N-myristoylation residue and specific amino acid sequences. We recently reported that Myr47 reduces the cellular uptake of HBV surface antigen (HBsAg, subviral particle of HBV) in the absence of NTCP expression. In this study, we analyzed how Myr47 reduces the cellular uptake of lipid nanoparticles (including liposomes (LPs) and HBsAg) without NTCP expression. By using Myr47 mutants lacking the HBV infection inhibitory activity, they could reduce the cellular uptake of LPs in an N-myristoylation-dependent manner and an amino acid sequence-independent manner, not only in human liver-derived cells but also in human non-liver-derived cells. Moreover, Myr47 and its mutants could reduce the interaction of LPs with apolipoprotein E3 (ApoE3) in an N-myristoylation-dependent manner regardless of their amino acid sequences. From these results, lipopeptides are generally anchored by inserting their myristoyl residue into the lipid bilayer and can inhibit the interaction of LPs/HBsAg with apolipoprotein, thereby reducing the cellular uptake of LPs/HBsAg. Similarly, Myr47 would interact with HBV, inhibiting the uptake of HBV into human hepatic cells, while the inhibitory effect of Myr47 may be secondary to its ability to protect against HBV infection. Full article
(This article belongs to the Special Issue Hepatitis B Virus: Its Life Cycle and the Therapeutic Targets)
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Review

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Review
Chronic Hepatitis B Treatment Strategies Using Polymerase Inhibitor-Based Combination Therapy
Viruses 2021, 13(9), 1691; https://doi.org/10.3390/v13091691 (registering DOI) - 26 Aug 2021
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Abstract
Viral polymerase is an essential enzyme for the amplification of the viral genome and is one of the major targets of antiviral therapies. However, a serious concern to be solved in hepatitis B virus (HBV) infection is the difficulty of eliminating covalently closed [...] Read more.
Viral polymerase is an essential enzyme for the amplification of the viral genome and is one of the major targets of antiviral therapies. However, a serious concern to be solved in hepatitis B virus (HBV) infection is the difficulty of eliminating covalently closed circular (ccc) DNA. More recently, therapeutic strategies targeting various stages of the HBV lifecycle have been attempted. Although cccDNA-targeted therapies are attractive, there are still many problems to be overcome, and the development of novel polymerase inhibitors remains an important issue. Interferons and nucleos(t)ide reverse transcriptase inhibitors (NRTIs) are the only therapeutic options currently available for HBV infection. Many studies have reported that the combination of interferons and NRTI causes the loss of hepatitis B surface antigen (HBsAg), which is suggestive of seroconversion. Although NRTIs do not directly target cccDNA, they can strongly reduce the serum viral DNA load and could suppress the recycling step of cccDNA formation, improve liver fibrosis/cirrhosis, and reduce the risk of hepatocellular carcinoma. Here, we review recent studies on combination therapies using polymerase inhibitors and discuss the future directions of therapeutic strategies for HBV infection. Full article
(This article belongs to the Special Issue Hepatitis B Virus: Its Life Cycle and the Therapeutic Targets)
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Other

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Protocol
Rapid and Robust Continuous Purification of High-Titer Hepatitis B Virus for In Vitro and In Vivo Applications
Viruses 2021, 13(8), 1503; https://doi.org/10.3390/v13081503 - 30 Jul 2021
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Abstract
Available treatments for hepatitis B can control the virus but are rarely curative. This led to a global initiative to design new curative therapies for the 257 million patients affected. Discovery and development of these new therapies is contingent upon functional in vitro [...] Read more.
Available treatments for hepatitis B can control the virus but are rarely curative. This led to a global initiative to design new curative therapies for the 257 million patients affected. Discovery and development of these new therapies is contingent upon functional in vitro and in vivo hepatitis B virus (HBV) infection models. However, low titer and impurity of conventional HBV stocks reduce significance of in vitro infections and moreover limit challenge doses in current in vivo models. Therefore, there is a critical need for a robust, simple and reproducible protocol to generate high-purity and high-titer infectious HBV stocks. Here, we outline a three-step protocol for continuous production of high-quality HBV stocks from supernatants of HBV-replicating cell lines. This purification process takes less than 6 h, yields to high-titer stocks (up to 1 × 1011 enveloped, DNA-containing HBV particles/mL each week), and is with minimal equipment easily adaptable to most laboratory settings. Full article
(This article belongs to the Special Issue Hepatitis B Virus: Its Life Cycle and the Therapeutic Targets)
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