Conflicting selection pressures target the NS3 protein in hepatitis C virus genotypes 1a and 1b.
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.
Irausquin
Stephanie Jiménez
SJ
Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA.
Hughes
Austin L
AL
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
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