Limits...
Variability and conservation in hepatitis B virus core protein.

Chain BM, Myers R - BMC Microbiol. (2005)

Bottom Line: Polymorphisms were found at 44 out of 185 amino acid positions analysed and were clustered predominantly in those parts of HBVc forming the outer surface and spike on intact capsid.The structural requirements of capsid assembly are likely to play a major role in limiting diversity.The phylogenetic analysis further suggests that immunological selection does not play a major role in driving HBVc diversity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Immunology and Molecular Pathology, University College London, W1T 4JF UK. b.chain@ucl.ac.uk

ABSTRACT

Background: Hepatitis B core protein (HBVc) has been extensively studied from both a structural and immunological point of view, but the evolutionary forces driving sequence variation within core are incompletely understood.

Results: In this study, the observed variation in HBVc protein sequence has been examined in a collection of a large number of HBVc protein sequences from public sequence repositories. An alignment of several hundred sequences was carried out, and used to analyse the distribution of polymorphisms along the HBVc. Polymorphisms were found at 44 out of 185 amino acid positions analysed and were clustered predominantly in those parts of HBVc forming the outer surface and spike on intact capsid. The relationship between HBVc diversity and HBV genotype was examined. The position of variable amino acids along the sequence was examined in terms of the structural constraints of capsid and envelope assembly, and also in terms of immunological recognition by T and B cells.

Conclusion: Over three quarters of amino acids within the HBVc sequence are non-polymorphic, and variation is focused to a few amino acids. Phylogenetic analysis suggests that core protein specific forces constrain its diversity within the context of overall HBV genome evolution. As a consequence, core protein is not a reliable predictor of virus genotype. The structural requirements of capsid assembly are likely to play a major role in limiting diversity. The phylogenetic analysis further suggests that immunological selection does not play a major role in driving HBVc diversity.

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Relationship between HBVc sequence and genotype. The 403 sequences from viruses of known genotype were aligned and compared to the consensus. The distance of each sequence from the consensus was calculated using maximum likely-hood model (Jones-Taylor-Thornton). The frequency distribution of distance from consensus was then plotted for each genotype A-D.
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Figure 2: Relationship between HBVc sequence and genotype. The 403 sequences from viruses of known genotype were aligned and compared to the consensus. The distance of each sequence from the consensus was calculated using maximum likely-hood model (Jones-Taylor-Thornton). The frequency distribution of distance from consensus was then plotted for each genotype A-D.

Mentions: Sequence variation in core protein may reflect the overall genotypic variation among HBV strains driven by drift or other unknown factors ("hitchhiking"). Alternatively, specific selection pressures may operate on HBVc driving diversity independently. In order to approach this question, the relationship between HBVc variation and HBV genotype was explored. Using text querying of the data base, a subset of 402 sequences were selected which had been assigned genotype A-D (these were the most frequent assigned genotypes within this set) by analysis of whole genome sequence or sequences outside the core region. These 402 core protein amino acid sequences were aligned and compared to each other and to the overall consensus sequence using Protdist, a Phylip program using the Jones-Taylor-Thornton model [15]. The distribution of distances between each sequence and the consensus was then plotted for each viral genotype as given in the database record (fig 2). The distance distribution profiles of the different genotypes were largely overlapping, suggesting that there was no correlation between distance from consensus and genotype.


Variability and conservation in hepatitis B virus core protein.

Chain BM, Myers R - BMC Microbiol. (2005)

Relationship between HBVc sequence and genotype. The 403 sequences from viruses of known genotype were aligned and compared to the consensus. The distance of each sequence from the consensus was calculated using maximum likely-hood model (Jones-Taylor-Thornton). The frequency distribution of distance from consensus was then plotted for each genotype A-D.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1173110&req=5

Figure 2: Relationship between HBVc sequence and genotype. The 403 sequences from viruses of known genotype were aligned and compared to the consensus. The distance of each sequence from the consensus was calculated using maximum likely-hood model (Jones-Taylor-Thornton). The frequency distribution of distance from consensus was then plotted for each genotype A-D.
Mentions: Sequence variation in core protein may reflect the overall genotypic variation among HBV strains driven by drift or other unknown factors ("hitchhiking"). Alternatively, specific selection pressures may operate on HBVc driving diversity independently. In order to approach this question, the relationship between HBVc variation and HBV genotype was explored. Using text querying of the data base, a subset of 402 sequences were selected which had been assigned genotype A-D (these were the most frequent assigned genotypes within this set) by analysis of whole genome sequence or sequences outside the core region. These 402 core protein amino acid sequences were aligned and compared to each other and to the overall consensus sequence using Protdist, a Phylip program using the Jones-Taylor-Thornton model [15]. The distribution of distances between each sequence and the consensus was then plotted for each viral genotype as given in the database record (fig 2). The distance distribution profiles of the different genotypes were largely overlapping, suggesting that there was no correlation between distance from consensus and genotype.

Bottom Line: Polymorphisms were found at 44 out of 185 amino acid positions analysed and were clustered predominantly in those parts of HBVc forming the outer surface and spike on intact capsid.The structural requirements of capsid assembly are likely to play a major role in limiting diversity.The phylogenetic analysis further suggests that immunological selection does not play a major role in driving HBVc diversity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Immunology and Molecular Pathology, University College London, W1T 4JF UK. b.chain@ucl.ac.uk

ABSTRACT

Background: Hepatitis B core protein (HBVc) has been extensively studied from both a structural and immunological point of view, but the evolutionary forces driving sequence variation within core are incompletely understood.

Results: In this study, the observed variation in HBVc protein sequence has been examined in a collection of a large number of HBVc protein sequences from public sequence repositories. An alignment of several hundred sequences was carried out, and used to analyse the distribution of polymorphisms along the HBVc. Polymorphisms were found at 44 out of 185 amino acid positions analysed and were clustered predominantly in those parts of HBVc forming the outer surface and spike on intact capsid. The relationship between HBVc diversity and HBV genotype was examined. The position of variable amino acids along the sequence was examined in terms of the structural constraints of capsid and envelope assembly, and also in terms of immunological recognition by T and B cells.

Conclusion: Over three quarters of amino acids within the HBVc sequence are non-polymorphic, and variation is focused to a few amino acids. Phylogenetic analysis suggests that core protein specific forces constrain its diversity within the context of overall HBV genome evolution. As a consequence, core protein is not a reliable predictor of virus genotype. The structural requirements of capsid assembly are likely to play a major role in limiting diversity. The phylogenetic analysis further suggests that immunological selection does not play a major role in driving HBVc diversity.

Show MeSH
Related in: MedlinePlus