A hepatitis B virus-derived human hepatic cell-specific heparin-binding peptide: identification and application to a drug delivery system

2019 ◽  
Vol 7 (1) ◽  
pp. 322-335 ◽  
Author(s):  
Qiushi Liu ◽  
Masaharu Somiya ◽  
Masumi Iijima ◽  
Kenji Tatematsu ◽  
Shun'ichi Kuroda
Keyword(s):  
Drug Delivery ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Peptide Identification ◽  
Binding Activity ◽  
Hepatic Cell ◽  
Heparin Binding ◽  
Hepatic Drug ◽  
System P ◽  
B Virus

Hepatitis B virus-mimicking nanoparticles containing doxorubicin for specific human hepatic drug delivery by heparin-binding activity.

scholarly journals Hepatitis B Virus X Protein and Simian Virus 5 V Protein Exhibit Similar UV-DDB1 Binding Properties To Mediate Distinct Activities

2003 ◽  
Vol 77 (11) ◽  
pp. 6274-6283 ◽  
Author(s):  
Olivier Leupin ◽  
Séverine Bontron ◽  
Michel Strubin
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Simian Virus ◽  
Binding Activity ◽  
X Protein ◽  
Binding Properties ◽  
V Protein ◽  
Dna Binding Activity ◽  
Simian Virus 5 ◽  
B Virus

ABSTRACT The UV-damaged DNA-binding activity protein (UV-DDB) consists of two subunits, DDB1 and DDB2, and functions in DNA repair and cell cycle regulation. The DDB1 subunit is a target for the hepatitis B virus X protein (HBx). Binding of HBx to DDB1 interferes with cell growth and viability in culture and has been implicated in the establishment of viral infection. DDB1 also interacts with the V proteins encoded by several paramyxoviruses including simian virus 5 (SV5), which prevent interferon signaling by targeting either STAT1 or STAT2 proteins for proteolysis. The role of V binding to DDB1, however, remains unclear. Here we show that the V protein of SV5 (SV5-V) and HBx exhibit strikingly similar DDB1 binding properties. Thus, SV5-V and HBx bind to DDB1 in a mutually exclusive manner, and SV5-V shares with HBx the ability to enhance the steady-state levels of DDB1 and to inhibit its association with DDB2. Yet only HBx induces cell death, and SV5-V can prevent HBx from doing so by blocking its interaction with DDB1. Binding of SV5-V to DDB1 may serve another function, since SV5-V shows a decreased ability to induce STAT1 degradation in cells expressing reduced amounts of DDB1. These findings demonstrate that HBx performs a unique function through its association with DDB1 for which SV5-V cannot substitute and suggest that SV5-V and HBx have evolved to bind DDB1 to achieve distinct functions, both by a mechanism that does not involve DDB2.

Drug Delivery Systems and Liver Targeting for the Improved Pharmacotherapy of the Hepatitis B Virus (HBV) Infection

2010 ◽  
Vol 27 (7) ◽  
pp. 1184-1202 ◽  
Author(s):  
María L. Cuestas ◽  
Verónica L. Mathet ◽  
José R. Oubiña ◽  
Alejandro Sosnik
Keyword(s):  
Drug Delivery ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Hbv Infection ◽  
Liver Targeting ◽  
B Virus

scholarly journals Screening and Evaluation of Novel Compounds against Hepatitis B Virus Polymerase Using Highly Purified Reverse Transcriptase Domain

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 840
Author(s):  
Eriko Ohsaki ◽  
Keiji Ueda
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Reverse Transcriptase ◽  
High Throughput Screening ◽  
Leukemia Virus ◽  
Binding Activity ◽  
Moloney Murine Leukemia Virus ◽  
Small Scale ◽  
B Virus ◽  
Pharmacologically Active

Hepatitis B virus (HBV) polymerase seems to be very hard to express and purify sufficiently, which has long hampered the generation of anti-HBV drugs based on the nature of the polymerase. To date, there has been no useful system developed for drug screening against HBV polymerase. In this study, we successfully obtained a highly purified reverse transcriptase (RT) domain of the polymerase, which has a template/primer and substrate binding activity, and established a novel high-throughput screening (HTS) system using purified RT protein for finding novel polymerase inhibitors. To examine whether the assay system provides reliable results, we tested the small scale screening using pharmacologically active compounds. As a result, the pilot screening identified already-known anti-viral polymerase agents. Then, we screened 20,000 chemical compounds and newly identified four hits. Several of these compounds inhibited not only the HBV RT substrate and/ template/primer binding activity, but also Moloney murine leukemia virus RT activity, which has an elongation activity. Finally, these candidates did show to be effective even in the cell-based assay. Our screening system provides a useful tool for searching candidate inhibitors against HBV.

Modular Hepatitis B Virus-like Particle Platform for Biosensing and Drug Delivery

ACS Nano ◽  
2020 ◽  
Vol 14 (10) ◽  
pp. 12642-12651
Author(s):  
Emily J. Hartzell ◽  
Rachel M. Lieser ◽  
Millicent O. Sullivan ◽  
Wilfred Chen
Keyword(s):  
Drug Delivery ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Virus Like Particle ◽  
B Virus

scholarly journals RNA-Binding Motif Protein 24 (RBM24) Is Involved in Pregenomic RNA Packaging by Mediating Interaction between Hepatitis B Virus Polymerase and the Epsilon Element

2019 ◽  
Vol 93 (6) ◽  
Author(s):  
Yongxuan Yao ◽  
Bo Yang ◽  
Yingshan Chen ◽  
Hui Wang ◽  
Xue Hu ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Rna Binding ◽  
Binding Activity ◽  
Hbv Infection ◽  
Binding Motif ◽  
Independent Manner ◽  
Stem Loop ◽  
Hbv Replication ◽  
B Virus

ABSTRACTEncapsidation of pregenomic RNA (pgRNA) is a crucial step in hepatitis B virus (HBV) replication. Binding by viral polymerase (Pol) to the epsilon stem-loop (ε) on the 5′-terminal region (TR) of pgRNA is required for pgRNA packaging. However, the detailed mechanism is not well understood. RNA-binding motif protein 24 (RBM24) inhibits core translation by binding to the 5′-TR of pgRNA. Here, we demonstrate that RBM24 is also involved in pgRNA packaging. RBM24 directly binds to the lower bulge of ε via RNA recognition submotifs (RNPs). RBM24 also interacts with Pol in an RNA-independent manner. The alanine-rich domain (ARD) of RBM24 and the reverse transcriptase (RT) domain of Pol are essential for binding between RBM24 and Pol. In addition, overexpression of RBM24 increases Pol-ε interaction, whereas RBM24 knockdown decreases the interaction. RBM24 was able to rescue binding between ε and mutant Pol lacking ε-binding activity, further showing that RBM24 mediates the interaction between Pol and ε by forming a Pol-RBM24-ε complex. Finally, RBM24 significantly promotes the packaging efficiency of pgRNA. In conclusion, RBM24 mediates Pol-ε interaction and formation of a Pol-RBM24-ε complex, which inhibits translation of pgRNA and results in pgRNA packing into capsids/virions for reverse transcription and DNA synthesis.IMPORTANCEHepatitis B virus (HBV) is a ubiquitous human pathogen, and HBV infection is a major global health burden. Chronic HBV infection is associated with the development of liver diseases, including fulminant hepatitis, hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. A currently approved vaccine can prevent HBV infection, and medications are able to reduce viral loads and prevent liver disease progression. However, current treatments rarely achieve a cure for chronic infection. Thus, it is important to gain insight into the mechanisms of HBV replication. In this study, we found that the host factor RBM24 is involved in pregenomic RNA (pgRNA) packaging and regulates HBV replication. These findings highlight a potential target for antiviral therapeutics of HBV infection.

scholarly journals Yield Optimisation of Hepatitis B Virus Core Particles in E. coli Expression System for Drug Delivery Applications

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Izzat Fahimuddin Bin Mohamed Suffian ◽  
Mitla Garcia-Maya ◽  
Paul Brown ◽  
Tam Bui ◽  
Yuya Nishimura ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Expression System ◽  
E Coli ◽  
Virus Core ◽  
B Virus ◽  
Drug Delivery Applications ◽  
Core Particles

scholarly journals Drug Delivery Strategies for Antivirals against Hepatitis B Virus

Viruses ◽  
2018 ◽  
Vol 10 (5) ◽  
pp. 267 ◽  
Author(s):  
Latavia Singh ◽  
Sunaina Indermun ◽  
Mershen Govender ◽  
Pradeep Kumar ◽  
Lisa du Toit ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
B Virus ◽  
Delivery Strategies

scholarly journals Hepatitis B virus polymerase inhibits the interferon-inducible MyD88 promoter by blocking nuclear translocation of Stat1

2007 ◽  
Vol 88 (12) ◽  
pp. 3260-3269 ◽  
Author(s):  
Min Wu ◽  
Yang Xu ◽  
Shanshan Lin ◽  
Xiaonan Zhang ◽  
Li Xiang ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Nuclear Translocation ◽  
Antagonistic Activity ◽  
Binding Activity ◽  
Primary Response ◽  
Dependent Manner ◽  
Interferon Stimulated Genes ◽  
Dna Binding Activity ◽  
B Virus

Previous studies have suggested that hepatitis B virus (HBV) blocks expression of the alpha interferon (IFN-α)-inducible myeloid differential primary response protein (MyD88) gene. To study the molecular mechanism(s) of the inhibition of MyD88 expression by HBV, MyD88 promoter reporter plasmids and vectors expressing different HBV viral proteins were constructed. Co-transfection experiments showed that IFN-induced MyD88 promoter activity was inhibited by HBV polymerase expression in a dose-dependent manner and that the terminal protein (TP) domain of HBV polymerase was responsible for this antagonistic activity. Analysis of site mutants showed that the region targeted by the polymerase protein contained the signal transducer and activator of transcription (Stat) binding site. Chromatin immunoprecipitation analysis showed that the IFN-induced DNA-binding activity of Stat1 was affected. Further study demonstrated that the HBV polymerase protein inhibited the Stat1 nuclear translocation induced by IFN-α, but did not induce Stat1 degradation nor interfere with its phosphorylation. In addition, HBV polymerase could inhibit the transcriptional activity of other IFN-stimulated response element-driven promoters and the expression of interferon-stimulated genes (ISGs), such as Stat1 and ISG15. In summary, these results indicate that HBV polymerase is a general inhibitor of IFN signalling and can inhibit IFN-inducible MyD88 expression by inhibiting the activity of the MyD88 promoter through blocking the nuclear translocation of Stat1.

scholarly journals Advances in Nanoparticle Drug Delivery Systems for Anti-Hepatitis B Virus Therapy: A Narrative Review

2021 ◽  
Vol 22 (20) ◽  
pp. 11227
Author(s):  
Jing Miao ◽  
Peng Gao ◽  
Qian Li ◽  
Kaifeng He ◽  
Liwen Zhang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Drug Targets ◽  
Drug Delivery Systems ◽  
Relevant Literature ◽  
Viral Disease ◽  
Delivery Systems ◽  
B Virus ◽  
Nanoparticle Drug Delivery

Chronic hepatitis B (CHB) is an infectious viral disease that is prevalent worldwide. Traditional nucleoside analogues, as well as the novel drug targets against hepatitis B virus (HBV), are associated with certain critical factors that influence the curative effect, such as biological stability and safety, effective drug delivery, and controlled release. Nanoparticle drug delivery systems have significant advantages and have provided a basis for the development of anti-HBV strategies. In this review, we aim to review the advances in nanoparticle drug delivery systems for anti-hepatitis B virus therapy by summarizing the relevant literature. First, we focus on the characteristics of nanoparticle drug delivery systems for anti-HBV therapy. Second, we discuss the nanoparticle delivery systems for anti-HBV nucleoside drugs, gene-based drugs, and vaccines. Lastly, we provide an overview of the prospects for nanoparticle-based anti-HBV agents.

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