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.
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.
Troesch
Myriam
M
Unité d'Immunopathologie Virale, Centre de Recherche, Hôpital Sainte-Justine, Montreal, Quebec, Canada.
Jalbert
Emilie
E
Canobio
Sophie
S
Boulassel
M Rachid
MR
Routy
Jean-Pierre
JP
Bernard
Nicole F
NF
Bruneau
Julie
J
Lapointe
Normand
N
Boucher
Marc
M
Soudeyns
Hugo
H
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
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