title: Immune evasion versus recovery after acute hepatitis C virus infection from a shared source.
abstract: Acute infection with hepatitis C virus (HCV) rarely is identified, and hence, the determinants of spontaneous resolution versus chronicity remain incompletely understood. In particular, because of the retrospective nature and unknown source of infection in most human studies, direct evidence for emergence of escape mutations in immunodominant major histocompatibility complex class I-restricted epitopes leading to immune evasion is extremely limited. In two patients infected accidentally with an identical HCV strain but who developed divergent outcomes, the total lack of HCV-specific CD4+ T cells in conjunction with vigorous CD8+ T cells that targeted a single epitope in one patient was associated with mutational escape and viral persistence. Statistical evidence for positive Darwinian selective pressure against an immunodominant epitope is presented. Wild-type cytotoxic T lymphocytes persisted even after the cognate antigen was no longer present.
authors.affiliation: Department of Medicine, Portland Veterans Administration Medical Center, Oregon Health Science University, Portland, OR 97239, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Tester
authors.forename: Susan
authors.initials: S
authors.lastname: Smyk-Pearson
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Anne
authors.initials: A
authors.lastname: Wertheimer
authors.forename: Ermei
authors.initials: E
authors.lastname: Yao
authors.forename: David M
authors.initials: DM
authors.lastname: Lewinsohn
authors.forename: John E
authors.initials: JE
authors.lastname: Tavis
authors.forename: Hugo R
authors.initials: HR
authors.lastname: Rosen
mesh_terms: D000208:Acute Disease; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000235:genetics / Q000276:immunology*; D018936:Hepatitis C Antigens / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics; D012641:Selection, Genetic; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D018936:Hepatitis C Antigens; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes