title: Conflicting selection pressures target the NS3 protein in hepatitis C virus genotypes 1a and 1b.
abstract: Analysis of complete polyprotein-encoding sequences of the two most prevalent genotypes of hepatitis C virus (HCV-1a and HCV-1b) revealed evidence of abundant, slightly deleterious nonsynonymous variants subject to ongoing purifying selection. In the case of both HCV-1a and HCV-1b, the NS3 protein demonstrated a high incidence of forward-and-backward or parallel nonsynonymous changes in CTL epitopes as measured by the phylogenetic consistency index. These results imply that certain nonsynonymous mutations have occurred frequently throughout the HCV-1a and HCV-1b phylogenies in the codons encoding the epitopes in NS3. This pattern is best explained by the frequent re-occurrence of the same set of escape mutations in CTL epitopes of NS3, which are selectively favored within hosts presenting the class I major histocompatability complex molecule, but subject to purifying selection in the population at large. This pattern was more pronounced in HCV-1b than in HCV-1a, suggesting that there may be differences between the two genotypes with respect to NS3's interaction with host immune recognition.
authors.affiliation: Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA.
authors.forename: Stephanie Jiménez
authors.initials: SJ
authors.lastname: Irausquin
authors.forename: Austin L
authors.initials: AL
authors.lastname: Hughes
mesh_terms: D000220:Adaptation, Biological; D019943:Amino Acid Substitution / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D019143:Evolution, Molecular; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D020125:Mutation, Missense; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000276:immunology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D018984:Epitopes, T-Lymphocyte; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases