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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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Sequence variation in the context of capsid structure. The crystal structure formed by four HBVc subunits was displayed and coloured using RasMol software. Positions containing 2 polymorphisms are coloured blue, 3 polymorphisms are coloured orange, and 4 or above are coloured red. Grey amino acids are invariant. a) The structure is displayed in ribbon form, showing a vertical section though the capsid, with two spikes projecting upwards, and the internal face of the capsid shown at the bottom of the picture. b) The structure is displayed in space fill. Upper Panel The structure is displayed so that the spikes and outward surface of the capsid are shown towards the viewer, and only the outer surface of the capsid is visible. Lower Panel The structure is rotated by 180 degrees so only the lower (inner) face of the capsid is visible.
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Figure 6: Sequence variation in the context of capsid structure. The crystal structure formed by four HBVc subunits was displayed and coloured using RasMol software. Positions containing 2 polymorphisms are coloured blue, 3 polymorphisms are coloured orange, and 4 or above are coloured red. Grey amino acids are invariant. a) The structure is displayed in ribbon form, showing a vertical section though the capsid, with two spikes projecting upwards, and the internal face of the capsid shown at the bottom of the picture. b) The structure is displayed in space fill. Upper Panel The structure is displayed so that the spikes and outward surface of the capsid are shown towards the viewer, and only the outer surface of the capsid is visible. Lower Panel The structure is rotated by 180 degrees so only the lower (inner) face of the capsid is visible.

Mentions: The sequence information in Additional file 1/fig 1 was rationalised on the three dimensional structure of the capsid obtained from the Brookhaven Data Base. As evident in fig 6 the variation in sequence is concentrated on the spikes at the outer surface of the capsids. All the amino acids with three or more variants are found on the outer surface of the capsid (fig 6b upper panel) while the internal surface facing the capsid lumen are relatively conserved (fig 6b, lower panel).


Variability and conservation in hepatitis B virus core protein.

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

Sequence variation in the context of capsid structure. The crystal structure formed by four HBVc subunits was displayed and coloured using RasMol software. Positions containing 2 polymorphisms are coloured blue, 3 polymorphisms are coloured orange, and 4 or above are coloured red. Grey amino acids are invariant. a) The structure is displayed in ribbon form, showing a vertical section though the capsid, with two spikes projecting upwards, and the internal face of the capsid shown at the bottom of the picture. b) The structure is displayed in space fill. Upper Panel The structure is displayed so that the spikes and outward surface of the capsid are shown towards the viewer, and only the outer surface of the capsid is visible. Lower Panel The structure is rotated by 180 degrees so only the lower (inner) face of the capsid is visible.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC1173110&req=5

Figure 6: Sequence variation in the context of capsid structure. The crystal structure formed by four HBVc subunits was displayed and coloured using RasMol software. Positions containing 2 polymorphisms are coloured blue, 3 polymorphisms are coloured orange, and 4 or above are coloured red. Grey amino acids are invariant. a) The structure is displayed in ribbon form, showing a vertical section though the capsid, with two spikes projecting upwards, and the internal face of the capsid shown at the bottom of the picture. b) The structure is displayed in space fill. Upper Panel The structure is displayed so that the spikes and outward surface of the capsid are shown towards the viewer, and only the outer surface of the capsid is visible. Lower Panel The structure is rotated by 180 degrees so only the lower (inner) face of the capsid is visible.
Mentions: The sequence information in Additional file 1/fig 1 was rationalised on the three dimensional structure of the capsid obtained from the Brookhaven Data Base. As evident in fig 6 the variation in sequence is concentrated on the spikes at the outer surface of the capsids. All the amino acids with three or more variants are found on the outer surface of the capsid (fig 6b upper panel) while the internal surface facing the capsid lumen are relatively conserved (fig 6b, lower panel).

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