ArticlePloS one2013
Computational evolutionary analysis of the overlapped surface (S) and polymerase (P) region in hepatitis B virus indicates the spacer domain in P is crucial for survival.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- From Genome Diversity to Inferred Functional Constraints: An Integrated Evolutionary Analysis of Hepatitis B Virus Genotype F.International journal of molecular sciences · 2026Article
- Mutational landscape of the surface antigen of hepatitis B virus in patients with hepatocellular carcinoma.Gut pathogens · 2025Article
- Generation of Replication-Competent Hepatitis B Virus Harboring Tagged Polymerase for Visualization and Quantification of the Infection.Microbiology and immunology · 2025Article
- Spacer Domain in Hepatitis B Virus Polymerase: Plugging a Hole or Performing a Role?Journal of virology · 2022Review
- Molecular Mechanisms during Hepatitis B Infection and the Effects of the Virus Variability.Viruses · 2021Review
- Phylogeographic Genetic Diversity in the White Sucker Hepatitis B Virus across the Great Lakes Region and Alberta, Canada.Viruses · 2021Article
- The characteristic of the synonymous codon usage and phylogenetic analysis of hepatitis B virus.Genes & genomics · 2020Article
- Discovery and Selection of Hepatitis B Virus-Derived T Cell Epitopes for Global Immunotherapy Based on Viral Indispensability, Conservation, and HLA-Binding Strength.Journal of virology · 2020Article
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- Insights From Deep Sequencing of the HBV Genome-Unique, Tiny, and Misunderstood.Gastroenterology · 2019Review
- Adaptive evolution of proteins in hepatitis B virus during divergence of genotypes.Scientific reports · 2017Article
- Mutations in hepatitis B virus polymerase are associated with the postoperative survival of hepatocellular carcinoma patients.PloS one · 2017Article
- Bioinformatic Identification of Rare Codon Clusters (RCCs) in HBV Genome and Evaluation of RCCs in Proteins Structure of Hepatitis B Virus.Hepatitis monthly · 2016Article
- Molecular evolution of the capsid gene in human norovirus genogroup II.Scientific reports · 2016Article
- Impacts of the G145R Mutation on the Structure and Immunogenic Activity of the Hepatitis B Surface Antigen: A Computational Analysis.Hepatitis monthly · 2016Article
- The prevalence of mutations in the major hydrophilic region of the surface antigen of hepatitis B virus varies with subgenotype.Epidemiology and infection · 2015Article
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Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe Hepatitis B Virus (HBV) genome contains four ORFs, S (surface), P (polymerase), C (core) and X. S is completely overlapped by P and as a consequence the overlapping region is subject to distinctive evolutionary constraints compared to the remainder of the genome. Specifically, a non-synonymous substitution in one coding frame may produce a synonymous substitution in the alternative frame, suggesting a possible conflict between requirements for diversifying and purifying forces. To examine how these contrasting requirements are balanced within this region, we investigated the relationship amongst positive selection sites, conserved regions, epitopes and elements of protein structure to consider how HBV balances the contrasting evolutionary pressures. METHODOLOGY/
results323 HBV genotype D genome sequences were collected and analyzed to identify sites under positive selection and highly conserved regions. Epitopes sequences were retrieved from previously published experimental studies stored in the Immune Epitope Database. Predicted secondary structures were used to investigate the association between structure and conservation. Entropy was used as a measure of conservation and bivariate logistic regression was used to investigate the relationship between positive selection/conserved sites and epitope/secondary structure regions. Our results indicate: (i) conservation in S is primarily dictated by α-helix elements in the protein structure, (ii) variable residues are mainly located in PreS, the major hydrophilic region (MHR) and the C-terminus, (iii) epitopes in S, which are directly targeted by the host immune system, are significantly associated with sites under positive selection.
conclusionsThe highly variable spacer domain in P, which corresponds to PreS in S, appears to act as a harbor for the accumulation of mutations that can provide flexibility for conformational changes and responding to immune pressure.
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