title: Escape mutations alter proteasome processing of major histocompatibility complex class I-restricted epitopes in persistent hepatitis C virus infection.
abstract: Mutations in hepatitis C virus (HCV) genomes facilitate escape from virus-specific CD8+ T lymphocytes in persistently infected chimpanzees. Our previous studies demonstrated that many of the amino acid substitutions in HCV epitopes prevented T-cell receptor recognition or binding to class I major histocompatibility complex molecules. Here we report that mutations within HCV epitopes also cause their destruction by changing the pattern of proteasome digestion. This mechanism of immune evasion provides further evidence of the potency of CD8+ T-cell selection pressure against HCV and should be considered when evaluating the significance of mutations in viral genomes from persistently infected chimpanzees and humans.
authors.affiliation: Center for Vaccines and Immunity, Children's Hospital, WA4011, 700 Children's Dr., Columbus, OH 43205, USA.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kimura
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Gushima
authors.forename: Sharad
authors.initials: S
authors.lastname: Rawale
authors.forename: Pravin
authors.initials: P
authors.lastname: Kaumaya
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Walker
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D004195:Disease Models, Animal; D006526:Hepatitis C / Q000235:genetics*; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D002679:Pan troglodytes; D046988:Proteasome Endopeptidase Complex / Q000235:genetics*; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
chemical_list: C093542:NS4 protein, hepatitis C virus; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; D046988:Proteasome Endopeptidase Complex