ArticleJournal of virology2009
Characterization of genotype-specific carboxyl-terminal cleavage sites of hepatitis B virus e antigen precursor and identification of furin as the candidate enzyme.
Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed.
- Hepatitis B Virus e Antigen in Mother-to-Child Transmission and Clinical Management of Hepatitis B.Viruses · 2025Review
- Beyond Processing: Furin as a Central Hub in Viral Pathogenesis and Genetic Susceptibility.Biomolecules · 2025Review
- HBV p22-interacting protein C1QBP inhibits viral replication through impeding nucleocapsid formation and nuclear import.PLoS pathogens · 2025Article
- Article
- NEDD4 family ubiquitin ligase AIP4 interacts with Alix to enable HBV naked capsid egress in an Alix ubiquitination-independent manner.PLoS pathogens · 2024Article
- Biology of the hepatitis B virus (HBV) core and capsid assembly modulators (CAMs) for chronic hepatitis B (CHB) cure.Global health & medicine · 2023Review
- Pre- and Post-Transcriptional Control of HBV Gene Expression: The Road Traveled towards the New Paradigm of HBx, Its Isoforms, and Their Diverse Functions.Biomedicines · 2023Review
- The Complex Role of HBeAg and Its Precursors in the Pathway to Hepatocellular Carcinoma.Viruses · 2023Review
- Screening of an epigenetic compound library identifies BRD4 as a potential antiviral target for hepatitis B virus covalently closed circular DNA transcription.Antiviral research · 2023Article
- Article
- A second functional furin site in the SARS-CoV-2 spike protein.Emerging microbes & infections · 2022Article
- Trends of hepatitis B virus genotype distribution in chronic hepatitis B patients in Japan.Journal of gastroenterology · 2022Article
- A roadmap for serum biomarkers for hepatitis B virus: current status and future outlook.Nature reviews. Gastroenterology & hepatology · 2022Review
- Autophagic membranes participate in hepatitis B virus nucleocapsid assembly, precore and core protein trafficking, and viral release.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Biogenesis of hepatitis B virus e antigen is driven by translocon-associated protein complex and regulated by conserved cysteine residues within its signal peptide sequence.The FEBS journal · 2022Article
- 5' preS1 Mutations To Prevent Large Envelope Protein Expression from Hepatitis B Virus Genotype A or Genotype D Markedly Increase Polymerase-Envelope Fusion Protein.Journal of virology · 2022Article
- Precore/core mutations of hepatitis B virus genotype D arising in different states of infection.Clinical and experimental hepatology · 2022Article
- Capsid Assembly Modulators as Antiviral Agents against HBV: Molecular Mechanisms and Clinical Perspectives.Journal of clinical medicine · 2022Review
- Specific determination of hepatitis B e antigen by antibodies targeting precore unique epitope facilitates clinical diagnosis and drug evaluation against hepatitis B virus infection.Emerging microbes & infections · 2021Article
- Hepatitis B virus e antigen and viral persistence.Current opinion in virology · 2021Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Hepatitis B e antigen (HBeAg) is a secreted version of hepatitis B virus (HBV) core protein that promotes immune tolerance and persistent infection. It is derived from a translation product of the precore/core gene by two proteolytic cleavage events: removal of the amino-terminal signal peptide and removal of the carboxyl-terminal arginine-rich sequence. Four RXXR motifs are present at the carboxyl terminus of the HBeAg precursor, with the first two fused as (151)RRGRSPR(157). Genotype A possesses two extra amino acids at the first motif ((151)RRDRGRSPR(159)), which weakens the first motif and separates it from the second one. Western blot analysis of patient sera revealed a single HBeAg form for genotypes B to D but two additional forms of larger sizes for genotype A. Site-directed mutagenesis and transfection experiments with human hepatoma cell lines indicated that HBeAg of genotype B is derived from cleavage at the first ((151)RRGR(154)) motif. The major HBeAg form of genotype A corresponds to cleavage at the second ((156)RSPR(159)) motif, and the other two forms are cleavage products of the first ((151)RRDR(154)) and third ((166)RRRR(169)) motifs, respectively. Only the cleavage product of the third motif of genotype A was observed in furin-deficient LoVo cells, and an inhibitor of furin-like proprotein convertases blocked cleavage of the first and second motifs in human hepatoma cells. In conclusion, our study reveals genotypic differences in HBeAg processing and implicates furin as the major enzyme involved in the cleavage of the first and second RXXR motifs.
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