The full repertoire of hepatitis B virus (HBV)
peptides that bind to the common HLA class I molecules found in areas with a high prevalence of chronic HBV
infection has not been determined. This information may be useful for designing
immunotherapies for
chronic hepatitis B. We identified
amino acid residues under positive selection pressure in the HBV core gene by phylogenetic analysis of cloned DNA sequences obtained from HBV
DNA extracted from the sera of Tongan subjects with inactive,
HBeAg-negative chronic HBV
infections. The repertoires of positively selected sites in groups of subjects who were homozygous for either
HLA-B*4001 (n = 10) or
HLA-B*5602 (n = 7) were compared. We identified 13
amino acid sites under positive selection pressure. A significant association between an HLA class I allele and the presence of nonsynonymous mutations was found at five of these sites.
HLA-B*4001 was associated with mutations at E77 (P = 0.05) and E113 (P = 0.002), and
HLA-B*5602 was associated with mutations at S21 (P = 0.02). In addition,
amino acid mutations at V13 (P = 0.03) and E14 (P = 0.01) were more common in the seven subjects with an
HLA-A*02 allele. In summary, we have developed an assay that can identify associations between HLA class I alleles and HBV core gene
amino acids that mutate in response to selection pressure. This is consistent with published evidence that CD8(+) T cells have a role in suppressing viral replication in inactive,
HBeAg-negative chronic HBV
infection. This assay may be useful for identifying the clinically significant HBV
peptides that bind to common HLA class I molecules.