title: Hepatitis C virus (HCV) sequence variation induces an HCV-specific T-cell phenotype analogous to spontaneous resolution.
abstract: Hepatitis C virus (HCV)-specific CD8(+) T cells in persistent HCV infection are low in frequency and paradoxically show a phenotype associated with controlled infections, expressing the memory marker CD127. We addressed to what extent this phenotype is dependent on the presence of cognate antigen. We analyzed virus-specific responses in acute and chronic HCV infections and sequenced autologous virus. We show that CD127 expression is associated with decreased antigenic stimulation after either viral clearance or viral variation. Our data indicate that most CD8 T-cell responses in chronic HCV infection do not target the circulating virus and that the appearance of HCV-specific CD127(+) T cells is driven by viral variation.
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. vkasprowicz@partners.org
authors.forename: Victoria
authors.initials: V
authors.lastname: Kasprowicz
authors.forename: Yu-Hoi
authors.initials: YH
authors.lastname: Kang
authors.forename: Michaela
authors.initials: M
authors.lastname: Lucas
authors.forename: Julian
authors.initials: J
authors.lastname: Schulze zur Wiesch
authors.forename: Thomas
authors.initials: T
authors.lastname: Kuntzen
authors.forename: Vicki
authors.initials: V
authors.lastname: Fleming
authors.forename: Brian E
authors.initials: BE
authors.lastname: Nolan
authors.forename: Steven
authors.initials: S
authors.lastname: Longworth
authors.forename: Andrew
authors.initials: A
authors.lastname: Berical
authors.forename: Bertram
authors.initials: B
authors.lastname: Bengsch
authors.forename: Robert
authors.initials: R
authors.lastname: Thimme
authors.forename: Lia
authors.initials: L
authors.lastname: Lewis-Ximenez
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.forename: Arthur Y
authors.initials: AY
authors.lastname: Kim
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
authors.forename: Georg M
authors.initials: GM
authors.lastname: Lauer
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000628:therapy / Q000821:virology; D006801:Humans; D053699:Interleukin-7 Receptor alpha Subunit / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D053699:Interleukin-7 Receptor alpha Subunit