title: Impact of viral selected mutations on T cell mediated immunity in chronically evolving and self limiting acute HCV infection.
abstract: The ability of HCV to mutate in response to cytotoxic T lymphocyte (CTL) pressure is increasingly recognized, but the influence of such a mechanism in viral persistence and final disease outcome has not been ascertained. In this study, we performed a detailed longitudinal analysis of cell mediated immunity and HCV evolution in two self limiting and two chronically evolving HCV acutely infected patients, one of whom transiently controlled viremia. Amino acid mutations in immunodominant regions of viruses were observed in all patients, although they conferred viral escape from CTL responses only in chronically infected individuals. Resurgence of viremia coincided with the replacement of the original virus quasispecies with mutant viruses that had escaped recognition by primary CD8(+) T cell responses and infection persisted in the presence of variant viruses which were less efficiently recognized by preexisting and de novo induced T cell responses.
authors.affiliation: Department of Cellular and Developmental Biology, Sapienza University of Rome, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Guglietta
authors.forename: Anna Rosa
authors.initials: AR
authors.lastname: Garbuglia
authors.forename: Leonidas
authors.initials: L
authors.lastname: Salichos
authors.forename: Lionello
authors.initials: L
authors.lastname: Ruggeri
authors.forename: Antonella
authors.initials: A
authors.lastname: Folgori
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Perrone
authors.forename: Cristina
authors.initials: C
authors.lastname: Camperio
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mellace
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Maio
authors.forename: Patrizia
authors.initials: P
authors.lastname: Maio
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Capobianchi
authors.forename: Enea
authors.initials: E
authors.lastname: Spada
authors.forename: Nicola
authors.initials: N
authors.lastname: Gargano
authors.forename: Cristiano
authors.initials: C
authors.lastname: Scottà
authors.forename: Enza
authors.initials: E
authors.lastname: Piccolella
authors.forename: Paola
authors.initials: P
authors.lastname: Del Porto
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D019143:Evolution, Molecular; D005260:Female; D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology; D006801:Humans; D007111:Immunity, Cellular; D016056:Immunodominant Epitopes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D016415:Sequence Alignment; D017423:Sequence Analysis, RNA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D014766:Viremia / Q000276:immunology / Q000821:virology
chemical_list: D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes