The effect of naturally occurring hepatitis B virus promoter deletions on promoter activity and mRNA initiation in vitro

ABSTRACT In chronic hepatitis B virus (HBV) infections, one of the most common mutations to the virus occurs at amino acid 97 of the core protein, where leucine replaces either phenylalanine or isoleucine, depending on strain. This mutation correlates with changes in viral nucleic acid metabolism and/or secretion. We hypothesize that this phenotype is due in part to altered core assembly, a process required for DNA synthesis. We examined in vitro assembly of empty HBV capsids from wild-type and F97L core protein assembly domains. The mutation enhanced both the rate and extent of assembly relative to those for the wild-type protein. The difference between the two proteins was most obvious in the temperature dependence of assembly, which was dramatically stronger for the mutant protein, indicating a much more positive enthalpy. Since the structures of the mutant and wild-type capsids are essentially the same and the mutation is not involved in the contact between dimers, we suggest that the F97L mutation affects the dynamic behavior of dimer and capsid.

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Green tea extract and its major component epigallocatechin gallate inhibits hepatitis B virus in vitro

Antiviral Research ◽

10.1016/j.antiviral.2007.11.011 ◽

2008 ◽

Vol 78 (3) ◽

pp. 242-249 ◽

Cited By ~ 54

Author(s):

Jun Xu ◽

Jue Wang ◽

Fei Deng ◽

Zhihong Hu ◽

Hualin Wang

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Green Tea ◽

Epigallocatechin Gallate ◽

Green Tea Extract ◽

B Virus ◽

Tea Extract

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Generation of Full-Length Functional Antibody against PreS2 of Hepatitis B Virus in Hepatic Cells In Vitro from Bicistrons Mediated by Gutless Adenovirus

BioDrugs ◽

10.2165/11316940-000000000-00000 ◽

2009 ◽

Vol 23 (6) ◽

pp. 391-397

Author(s):

Yuexiang Yin ◽

Fang Lin ◽

Qiang Zhuang ◽

Li Liu ◽

Cheng Qian

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Full Length ◽

Hepatic Cells ◽

B Virus

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Epitope–Paratope Interaction of a Neutralizing Human Anti-Hepatitis B Virus PreS1 Antibody That Recognizes the Receptor-Binding Motif

Vaccines ◽

10.3390/vaccines9070754 ◽

2021 ◽

Vol 9 (7) ◽

pp. 754

Author(s):

Jisu Hong ◽

Youngjin Choi ◽

Yoonjoo Choi ◽

Jiwoo Lee ◽

Hyo Jeong Hong

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Receptor Binding ◽

Neutralizing Antibody ◽

Hbv Infection ◽

Binding Motif ◽

Alanine Scanning Mutagenesis ◽

B Virus ◽

Complementarity Determining Regions

Hepatitis B virus (HBV) is a global health burden that causes acute and chronic hepatitis. To develop an HBV-neutralizing antibody that effectively prevents HBV infection, we previously generated a human anti-preS1 monoclonal antibody (1A8) that binds to genotypes A–D and validated its HBV-neutralizing activity in vitro. In the present study, we aimed to determine the fine epitope and paratope of 1A8 to understand the mechanism of HBV neutralization. We performed alanine-scanning mutagenesis on the preS1 (aa 19–34, genotype C) and the heavy (HCDR) and light (LCDR) chain complementarity-determining regions. The 1A8 recognized the three residues (Leu22, Gly23, and Phe25) within the highly conserved receptor-binding motif (NPLGFFP) of the preS1, while four CDR residues of 1A8 were critical in antigen binding. Structural analysis of the epitope–paratope interaction by molecular modeling revealed that Leu100 in the HCDR3, Ala50 in the HCDR2, and Tyr96 in the LCDR3 closely interacted with Leu22, Gly23, and Phe25 of the preS1. Additionally, we found that 1A8 also binds to the receptor-binding motif (NPLGFLP) of infrequently occurring HBV. The results suggest that 1A8 may broadly and effectively block HBV entry and thus have potential as a promising candidate for the prevention and treatment of HBV infection.

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