title: Characterization of humoral and cell-mediated immune responses directed against hepatitis C virus F protein in subjects co-infected with hepatitis C virus and HIV-1.
abstract: BACKGROUND
  Hepatitis C virus (HCV) F protein is encoded in an alternate reading frame overlapping the core protein region. Its precise sequence, biological function and mode of expression are currently unclear. This study was conducted to examine the prevalence and characteristics of host humoral and cell-mediated immune responses directed against F protein in patients co-infected with HCV and HIV-1.
  
  
  METHODS
  Mutations were introduced to allow the expression of HCV-1a F protein in the absence of core. This recombinant and a truncated form lacking the first 11 amino acid residues shared with core were expressed in Escherichia coli, and their amino acid sequences were verified by mass spectrometry. Vaccinia-F protein recombinants were used to test F protein-specific cytotoxic T lymphocyte (CTL) activity. The binding of F protein-derived peptides to HLA-A*0201 was studied to identify putative CTL epitopes.
  
  
  RESULTS
  Sera from 23 of 39 patients infected with various HCV genotypes recognized the truncated form, including 13 of 25 subjects co-infected with HIV-1, indicative of antigenic crossreactivity and consistent with the conservation of F protein coding sequences between HCV genotypes. Crossreactive F protein-specific CTL precursors were detected in nine of 11 HCV-infected subjects, including seven of nine patients co-infected with HCV and HIV-1. Finally, three novel putative HLA-A*0201-restricted CTL epitopes were identified.
  
  
  CONCLUSIONS
  These results indicate that patients co-infected with HCV and HIV-1 can mount immunoglobulin and CTL responses directed against HCV F protein that are fully comparable in scope and magnitude with those observed in individuals infected with HCV alone.
authors.affiliation: Unité d'Immunopathologie Virale, Centre de Recherche, Hôpital Sainte-Justine, Montreal, Quebec, Canada.
authors.forename: Myriam
authors.initials: M
authors.lastname: Troesch
authors.forename: Emilie
authors.initials: E
authors.lastname: Jalbert
authors.forename: Sophie
authors.initials: S
authors.lastname: Canobio
authors.forename: M Rachid
authors.initials: MR
authors.lastname: Boulassel
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Bernard
authors.forename: Julie
authors.initials: J
authors.lastname: Bruneau
authors.forename: Normand
authors.initials: N
authors.lastname: Lapointe
authors.forename: Marc
authors.initials: M
authors.lastname: Boucher
authors.forename: Hugo
authors.initials: H
authors.lastname: Soudeyns
mesh_terms: D000328:Adult; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D015234:HLA-A Antigens; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014615:Vaccinia / Q000276:immunology; D014758:Viral Core Proteins / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
chemical_list: D000939:Epitopes; D015234:HLA-A Antigens; D018937:Hepatitis C Antibodies; D011994:Recombinant Proteins; D014758:Viral Core Proteins; D014764:Viral Proteins; C433031:hepatitis C protein F, Hepatitis C virus