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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Analysis of the relationships between HBVc sequences. All the sequences were classified and plotted as an unrooted tree using the Fitsch Margoliash criterion (Kitsch, see Materials and Methods). Where known the genotype is indicated by colour coding (Yellow = A, Green = B, Blue = C, Red = D). Sequences of unknown genotype are in black.
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Figure 3: Analysis of the relationships between HBVc sequences. All the sequences were classified and plotted as an unrooted tree using the Fitsch Margoliash criterion (Kitsch, see Materials and Methods). Where known the genotype is indicated by colour coding (Yellow = A, Green = B, Blue = C, Red = D). Sequences of unknown genotype are in black.

Mentions: In an alternative approach, the relationship between all the different core sequences was determined using Fitch-Margoliash least squares analysis, and plotted as an unrooted tree (fig 3). The different genotypes of each virus are colour coded. Although some broad clustering of genotypes was evident, a significant amount of "mixing" can be observed. Similar qualitative results were obtained when phylogeny was determined by Neighbour Joining analysis (using Phylip program Neighbor) or by parsimony (using Phylip program ProtPars).


Variability and conservation in hepatitis B virus core protein.

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

Analysis of the relationships between HBVc sequences. All the sequences were classified and plotted as an unrooted tree using the Fitsch Margoliash criterion (Kitsch, see Materials and Methods). Where known the genotype is indicated by colour coding (Yellow = A, Green = B, Blue = C, Red = D). Sequences of unknown genotype are in black.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Analysis of the relationships between HBVc sequences. All the sequences were classified and plotted as an unrooted tree using the Fitsch Margoliash criterion (Kitsch, see Materials and Methods). Where known the genotype is indicated by colour coding (Yellow = A, Green = B, Blue = C, Red = D). Sequences of unknown genotype are in black.
Mentions: In an alternative approach, the relationship between all the different core sequences was determined using Fitch-Margoliash least squares analysis, and plotted as an unrooted tree (fig 3). The different genotypes of each virus are colour coded. Although some broad clustering of genotypes was evident, a significant amount of "mixing" can be observed. Similar qualitative results were obtained when phylogeny was determined by Neighbour Joining analysis (using Phylip program Neighbor) or by parsimony (using Phylip program ProtPars).

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