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

Myriam Troesch, Emilie Jalbert, Sophie Canobio, M. Rachid Boulassel, Jean Pierre Routy, Nicole F. Bernard, Julie Bruneau, Normand Lapointe, Marc Boucher, Hugo Soudeyns

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)775-784
Number of pages10
JournalAIDS
Volume19
Issue number8
Publication statusPublished - May 20 2005

Fingerprint

Hepacivirus
HIV-1
Cytotoxic T-Lymphocytes
T-Lymphocyte Epitopes
Proteins
Genotype
Vaccinia
Reading Frames
hepatitis C protein F, Hepatitis C virus
Recombinant Proteins
Immunoglobulins
Amino Acid Sequence
Mass Spectrometry
Carrier Proteins
Escherichia coli
Amino Acids
Peptides
Mutation
Serum

Keywords

  • Alternate reading frame protein
  • Co-infection
  • Crossreactivity
  • Cytotoxic T lymphocytes
  • Hepatitis C

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

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. / Troesch, Myriam; Jalbert, Emilie; Canobio, Sophie; Boulassel, M. Rachid; Routy, Jean Pierre; Bernard, Nicole F.; Bruneau, Julie; Lapointe, Normand; Boucher, Marc; Soudeyns, Hugo.

In: AIDS, Vol. 19, No. 8, 20.05.2005, p. 775-784.

Research output: Contribution to journalArticle

Troesch, M, Jalbert, E, Canobio, S, Boulassel, MR, Routy, JP, Bernard, NF, Bruneau, J, Lapointe, N, Boucher, M & Soudeyns, H 2005, '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', AIDS, vol. 19, no. 8, pp. 775-784.
Troesch, Myriam ; Jalbert, Emilie ; Canobio, Sophie ; Boulassel, M. Rachid ; Routy, Jean Pierre ; Bernard, Nicole F. ; Bruneau, Julie ; Lapointe, Normand ; Boucher, Marc ; Soudeyns, Hugo. / 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. In: AIDS. 2005 ; Vol. 19, No. 8. pp. 775-784.
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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 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.",
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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

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AU - Soudeyns, Hugo

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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.

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