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HBV core sequence: definition of genotype-specific variability and correlation with geographical origin
S M Jazayeri1, M Jazayeri, A A Basuni
1Division of Virology, Institute of Biomedical and Life Science, University of Glasgow, Glasgow, UK.
Journal of Viral Hepatitis
|October 27, 2004
Summary
Hepatitis B virus (HBV) core gene sequences reveal unique genetic markers for different geographical regions and subtypes. These variations, particularly in T cell epitopes, may influence the effectiveness of immunotherapies.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Hepatitis B virus (HBV) exhibits genetic diversity with eight genotypes and nine subtypes.
- Geographical origin influences sequence variations, particularly in the HBV surface gene.
Purpose of the Study:
- To compare HBV core gene sequences across different genotypes and geographical regions.
- To identify genetic markers for HBV subtype allocation and geographical origin.
- To investigate the impact of geographical and genotypic variations on T cell epitopes.
Main Methods:
- Comparative analysis of HBV core gene sequences.
- Identification of amino acid substitutions and nucleotide changes associated with specific genotypes, subtypes, and geographical origins.
- Mapping of amino acid residues within T cell epitopes.
Main Results:
- A combination of 24 amino acid substitutions at nine residues accurately allocated HBV sequences to subtypes.
- Six of these nine residues were located in T cell epitopes, varying by HBV geographical area and/or genotype.
- Thirty-seven nucleotide changes were uniquely associated with specific HBV genotypes and subtypes.
- Unique nucleotide and amino acid variants were identified in sequences from specific countries and subtypes (ayw2, adr).
- Specific nucleotide motifs were defined for isolates from Korea, India, China, Italy, and the Pacific region.
- Amino acid motifs common to Southeast Asian or Western populations were observed, irrespective of subtype.
Conclusions:
- HBV strains appear to spread within geographically constrained ethnic groups, leading to selection pressures that drive sequence variability within subtypes.
- Specific T cell epitopes are associated with geographical regions and ethnic groups, potentially impacting the design of immunomodulatory therapies for HBV.