Development of Human Antibody Inhibiting RNase H Activity of Polymerase of Hepatitis B Virus Using Phage Display Technique

2004 ◽  
Vol 4 (1) ◽  
pp. 16
Author(s):  
Seong-Rak Lee ◽  
Eun-Kyoung Song ◽  
Young-Joo Jeong ◽  
Young-Yi Lee ◽  
Ik-Jung Kim ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Phage Display ◽  
Rnase H ◽  
Human Antibody ◽  
Phage Display Technique ◽  
B Virus ◽  
Display Technique

scholarly journals Screening of binding protein of hepatitis B virus pre-pre-s promoter by phage display technique

2004 ◽  
Vol 12 (12) ◽  
pp. 2801-2804
Author(s):  
Yan-Ping Huang ◽  
Jun Cheng ◽  
Shu-Lin Zhang ◽  
Yan-Jie Yang ◽  
Xue-Song Gao ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Phage Display ◽  
Binding Protein ◽  
Phage Display Technique ◽  
B Virus ◽  
Display Technique

scholarly journals Hepatitis B virus polymerase restricts LINE-1 retrotransposition

2021 ◽  
Author(s):  
Yasuo Ariumi
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Rna Binding ◽  
Rnase H ◽  
Ribonuclease H ◽  
Independent Manner ◽  
Cytoplasmic Rna ◽  
B Virus ◽  
Long Interspersed Element ◽  
L1 Retrotransposon

Long interspersed element-1 (LINE-1, L1) retrotransposon composes about 17% of the human genome. However, genetic and biochemical interactions between L1 and hepatitis B virus (HBV) remain poorly understood. In this study, we found that HBV restricts L1 mobility without inhibiting the L1 promoter activity. Notably, HBV polymerase (Pol) strongly inhibited L1 retrotransposition in a reverse transcriptase (RT)-independent manner. Indeed, the ribonuclease H (RNase H) domain was essential for inhibition of L1 retrotransposition. L1 ORF1p RNA-binding protein predominantly localized into cytoplasmic RNA granule termed P-body. However, HBV Pol sequestered L1 ORF1p from P-body and colocalized with L1 ORF1p in cytoplasm, when both proteins were co-expressed. Altogether, HBV Pol seems to restrict L1 mobility through a sequestration of L1 ORF1p from P-body. Thus, these results suggest a novel function or activity of HBV Pol in regulation of L1 retrotransposition.

scholarly journals Detection of hepatitis B virus core antigen by phage display mediated TaqMan real-time immuno-PCR

2013 ◽  
Vol 187 (1) ◽  
pp. 121-126 ◽  
Author(s):  
Razieh Monjezi ◽  
Sheau Wei Tan ◽  
Beng Ti Tey ◽  
Chin Chin Sieo ◽  
Wen Siang Tan
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Phage Display ◽  
Real Time ◽  
Core Antigen ◽  
Virus Core ◽  
B Virus

123 STRUCTURE OF THE HEPATITIS B VIRUS RNase H, A TARGET FOR NEW ANTIVIRAL DRUG DEVELOPMENT, UNRAVELED BY ULTRA-DEEP PYROSEQUENCING AND MOLECULAR MODELING

2013 ◽  
Vol 58 ◽  
pp. S55
Author(s):  
J. Hayer ◽  
C. Rodriguez ◽  
G. Germanidis ◽  
G. Deleage ◽  
F. Zoulim ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Molecular Modeling ◽  
Hepatitis B ◽  
Drug Development ◽  
Antiviral Drug ◽  
Rnase H ◽  
B Virus

scholarly journals 3-Hydroxypyrimidine-2,4-Diones as Novel Hepatitis B Virus Antivirals Targeting the Viral Ribonuclease H

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Andrew D. Huber ◽  
Eleftherios Michailidis ◽  
Jing Tang ◽  
Maritza N. Puray-Chavez ◽  
Maria Boftsi ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Activity ◽  
Essential Role ◽  
Rnase H ◽  
Ribonuclease H ◽  
Hbv Replication ◽  
B Virus ◽  
Infected Cells ◽  
Micromolar Range

ABSTRACT Hepatitis B virus (HBV) RNase H (RNH) is an appealing therapeutic target due to its essential role in viral replication. RNH inhibitors (RNHIs) could help to more effectively control HBV infections. Here, we report 3-hydroxypyrimidine-2,4-diones as novel HBV RNHIs with antiviral activity. We synthesized and tested 52 analogs and found 4 that inhibit HBV RNH activity in infected cells. Importantly, 2 of these compounds inhibited HBV replication in the low micromolar range.

scholarly journals Synergistic Interactions between Hepatitis B Virus RNase H Antagonists and Other Inhibitors

2016 ◽  
Vol 61 (3) ◽  
Author(s):  
Elena Lomonosova ◽  
Adam Zlotnick ◽  
John E. Tavis
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Core Protein ◽  
Index Theorem ◽  
Rnase H ◽  
Mass Action ◽  
Significant Activity ◽  
B Virus ◽  
Mass Action Law

ABSTRACT Combination therapies are standard for management of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections; however, no such therapies are established for human hepatitis B virus (HBV). Recently, we identified several promising inhibitors of HBV RNase H (here simply RNase H) activity that have significant activity against viral replication in vitro. Here, we investigated the in vitro antiviral efficacy of combinations of two RNase H inhibitors with the current anti-HBV drug nucleoside analog lamivudine, with HAP12, an experimental core protein allosteric modulator, and with each other. Anti-HBV activities of the compounds were tested in a HepG2-derived cell line by monitoring intracellular core particle DNA levels, and cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. The antiviral efficiencies of the drug combinations were evaluated using the median-effect equation derived from the mass-action law principle and combination index theorem of Chou and Talalay. We found that combinations of two RNase H inhibitors from different chemical classes were synergistic with lamivudine against HBV DNA synthesis. Significant synergism was also observed for the combination of the two RNase H inhibitors. Combinations of RNase H inhibitors with HAP12 had additive antiviral effects. Enhanced cytotoxicity was not observed in the combination experiments. Because of these synergistic and additive effects, the antiviral activity of combinations of RNase H inhibitors with drugs that act by two different mechanisms and with each other can be achieved by administering the compounds in combination at doses below the respective single drug doses.

Induction of hepatitis B virus-specific cytotoxic T lymphocytes response in vivo by filamentous phage display vaccine

Vaccine ◽  
2001 ◽  
Vol 19 (20-22) ◽  
pp. 2918-2923 ◽  
Author(s):  
Ying Wan ◽  
Yuzhang Wu ◽  
Jiang Bian ◽  
XiangZhi Wang ◽  
Wei Zhou ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
T Lymphocytes ◽  
Hepatitis B ◽  
Phage Display ◽  
Cytotoxic T Lymphocytes ◽  
Filamentous Phage ◽  
B Virus

scholarly journals Residues Arg703, Asp777, and Arg781 of the RNase H Domain of Hepatitis B Virus Polymerase Are Critical for Viral DNA Synthesis

2013 ◽  
Vol 88 (1) ◽  
pp. 154-163 ◽  
Author(s):  
C. Ko ◽  
Y.-C. Shin ◽  
W.-J. Park ◽  
S. Kim ◽  
J. Kim ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Dna Synthesis ◽  
Rnase H ◽  
Viral Dna ◽  
B Virus

scholarly journals Properties of Monoclonal Antibodies Directed against Hepatitis B Virus Polymerase Protein

1999 ◽  
Vol 73 (5) ◽  
pp. 4188-4196 ◽  
Author(s):  
Jasper zu Putlitz ◽  
Robert E. Lanford ◽  
Rolf I. Carlson ◽  
Lena Notvall ◽  
Suzanne M. de la Monte ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Insect Cells ◽  
Rnase H ◽  
Hbv Replication ◽  
B Virus ◽  
Multifunctional Enzymes ◽  
Infected Insect

ABSTRACT Hepadnavirus polymerases are multifunctional enzymes that play critical roles during the viral life cycle but have been difficult to study due to a lack of a well-defined panel of monoclonal antibodies (MAbs). We have used recombinant human hepatitis B virus (HBV) polymerase (Pol) expressed in and purified from baculovirus-infected insect cells to generate a panel of six MAbs directed against HBV Pol protein. Such MAbs were subsequently characterized with respect to their isotypes and functions in analytical and preparative assays. Using these MAbs as probes together with various deletion mutants of Pol expressed in insect cells, we mapped the B-cell epitopes of Pol recognized by these MAbs to amino acids (aa) 8 to 20 and 20 to 30 in the terminal protein (TP) region of Pol, to aa 225 to 250 in the spacer region, and to aa 800 to 832 in the RNase H domain. Confocal microscopy and immunocytochemical studies using various Pol-specific MAbs revealed that the protein itself appears to be exclusively localized to the cytoplasm. Finally, MAbs specific for the TP domain, but not MAbs specific for the spacer or RNase H regions of Pol, appeared to inhibit Pol function in the in vitro priming assay, suggesting that antibody-mediated interference with TP may now be assessed in the context of HBV replication.

Sign in / Sign up

Export Citation Format

Share Document