title: Positive selection of cytotoxic T lymphocyte escape variants during acute hepatitis C virus infection.
abstract: Cellular immune responses are induced during hepatitis C virus (HCV) infection and acute-phase CD8+ T cells are supposed to play an important role in controlling viral replication. In chimpanzees, failure of CD8+ T cells to control HCV replication has been associated with acquisition of mutations in MHC class I-restricted epitopes. In humans, although selection of escape mutations in an immunodominant CTL epitope has been recently described, the overall impact of immune escape during acute HCV infection is unclear. Here, by performing an in depth analysis of the relationship between early cellular immune responses and viral evolution in a chronically evolving HCV acutely infected individual, we demonstrate: (i) the presence of a potent and focused CD8(+ T cell response against a novel epitope in the NS3 protein, (ii) the elimination of the quasi-species harboring the original amino acid sequence within this epitope, and (iii) the selection for a virus population bearing amino acid changes at a single residue within the cytotoxic T cell epitope that strongly diminished T cell recognition. These results support the view that acute-phase CD8+ T cell responses exert a biologically relevant pressure on HCV replication and that viruses escaping this host response could have a significant survival advantage.
authors.affiliation: Department of Cellular and Developmental Biology University of Rome La Sapienza, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Guglietta
authors.forename: Anna Rosa
authors.initials: AR
authors.lastname: Garbuglia
authors.forename: Valentina
authors.initials: V
authors.lastname: Pacciani
authors.forename: Cristiano
authors.initials: C
authors.lastname: Scottà
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Perrone
authors.forename: Luca
authors.initials: L
authors.lastname: Laurenti
authors.forename: Enea
authors.initials: E
authors.lastname: Spada
authors.forename: Alfonso
authors.initials: A
authors.lastname: Mele
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Capobianchi
authors.forename: Gloria
authors.initials: G
authors.lastname: Taliani
authors.forename: Antonella
authors.initials: A
authors.lastname: Folgori
authors.forename: Alessandra
authors.initials: A
authors.lastname: Vitelli
authors.forename: Lionello
authors.initials: L
authors.lastname: Ruggeri
authors.forename: Alfredo
authors.initials: A
authors.lastname: Nicosia
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; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D019143:Evolution, Molecular; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D017361:Viral Nonstructural Proteins; D007371:Interferon-gamma