title: Divergent and convergent evolution after a common-source outbreak of hepatitis C virus.
abstract: The genomic sequences of viruses that are highly mutable and cause chronic infection tend to diverge over time. We report that these changes represent both immune-driven selection and, in the absence of immune pressure, reversion toward an ancestral consensus. Sequence changes in hepatitis C virus (HCV) structural and nonstructural genes were studied in a cohort of women accidentally infected with HCV in a rare common-source outbreak. We compared sequences present in serum obtained 18-22 yr after infection to sequences present in the shared inoculum and found that HCV evolved along a distinct path in each woman. Amino acid substitutions in known epitopes were directed away from consensus in persons having the HLA allele associated with that epitope (immune selection), and toward consensus in those lacking the allele (reversion). These data suggest that vaccines for genetically diverse viruses may be more effective if they represent consensus sequence, rather than a human isolate.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. sray@jhmi.edu
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Ray
authors.forename: Liam
authors.initials: L
authors.lastname: Fanning
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Wang
authors.forename: Dale M
authors.initials: DM
authors.lastname: Netski
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kenny-Walsh
authors.forename: David L
authors.initials: DL
authors.lastname: Thomas
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics / Q000276:immunology*; D000818:Animals; D016384:Consensus Sequence / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D019143:Evolution, Molecular; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D018936:Hepatitis C Antigens / Q000235:genetics / Q000276:immunology; D051379:Mice; D012641:Selection, Genetic; D014761:Viral Hepatitis Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D018936:Hepatitis C Antigens; D014761:Viral Hepatitis Vaccines; D015678:Viral Structural Proteins