title: Evolution of cytotoxic T-lymphocyte epitopes in hepatitis B virus.
abstract: In hepatitis B virus (HBV), while mutations that escape from cytotoxic T-lymphocyte (CTL) recognition have been described it has been difficult to determine how natural selection by host CTL has influenced long-term evolution of HBV. We used statistical analysis of published HBV genomic sequences to examine the role of natural selection in evolution of CTL epitopes. Based on a phylogenetic analysis, we identified 25 pairs of closely related genomes isolated from different HBV genotypes and examined pattern of nucleotide substitution in genomic regions encoding well-characterized CTL epitopes. On average, both epitope and non-epitope regions are subject to purifying selection acting at non-synonymous sites. However, certain CTL epitopes showed a pattern of nucleotide substitution suggesting repeated positive selection across the population. The results support the hypothesis that CTL-driven selection has been an important factor in long-term evolution of HBV.
authors.affiliation: Department of Biology, Winthrop University, Rock Hill, SC 29733, USA.
authors.forename: Kristi M
authors.initials: KM
authors.lastname: Westover
authors.forename: Austin L
authors.initials: AL
authors.lastname: Hughes
mesh_terms: D000956:Antigens, Viral / Q000235:genetics* / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics*; D019143:Evolution, Molecular; D016679:Genome, Viral; D006509:Hepatitis B / Q000276:immunology / Q000821:virology; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D010802:Phylogeny; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D014764:Viral Proteins