TY - JOUR
T1 - 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
AU - Troesch, Myriam
AU - Jalbert, Emilie
AU - Canobio, Sophie
AU - Boulassel, M. Rachid
AU - Routy, Jean Pierre
AU - Bernard, Nicole F.
AU - Bruneau, Julie
AU - Lapointe, Normand
AU - Boucher, Marc
AU - Soudeyns, Hugo
PY - 2005/5/20
Y1 - 2005/5/20
N2 - 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 coinfected with HCV and HIV-1. Finally, three novel putative HLA-A*0201-restricted CTL epitopes were identified. Conclusion: 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.
AB - 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 coinfected with HCV and HIV-1. Finally, three novel putative HLA-A*0201-restricted CTL epitopes were identified. Conclusion: 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.
KW - Alternate reading frame protein
KW - Co-infection
KW - Crossreactivity
KW - Cytotoxic T lymphocytes
KW - Hepatitis C
UR - http://www.scopus.com/inward/record.url?scp=20644463921&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20644463921&partnerID=8YFLogxK
U2 - 10.1097/01.aids.0000168971.57681.6e
DO - 10.1097/01.aids.0000168971.57681.6e
M3 - Article
C2 - 15867491
AN - SCOPUS:20644463921
SN - 0269-9370
VL - 19
SP - 775
EP - 784
JO - AIDS
JF - AIDS
IS - 8
ER -