Memory T-cell-mediated immune responses specific to an alternative core protein in hepatitis C virus infection
| Autor: | Florence Komurian-Pradel, Blandine Duverger, L. Gebuhrer, Gláucia Paranhos-Baccalà, Jean Pierre Lavergne, Christine Bain, Claude Vieux, François Penin, Geneviève Inchauspé, Valérie Dubois, Peggy Parroche, Christian Trepo |
|---|---|
| Přispěvatelé: | Deleage, Gilbert |
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Adult
T-Lymphocytes Hepatitis C virus Hepacivirus Molecular Sequence Data Immunology Sequence Homology medicine.disease_cause Antiviral Agents Microbiology Virus Interferon-gamma Immune system Antigen Virology Ribavirin medicine [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Humans Amino Acid Sequence Viremia Antigens Viral Aged B-Lymphocytes biology Viral Core Proteins Interferon-alpha Hepatitis C Antibodies Middle Aged biology.organism_classification medicine.disease Hepatitis C Interleukin-10 Treatment Outcome medicine.anatomical_structure Insect Science biology.protein Pathogenesis and Immunity Antibody Viral hepatitis Immunologic Memory Memory T cell |
| Popis: | In vitro studies have described the synthesis of an alternative reading frame form of the hepatitis C virus (HCV) core protein that was named F protein or ARFP (alternative reading frame protein) and includes a domain coded by the +1 open reading frame of the RNA core coding region. The expression of this protein in HCV-infected patients remains controversial. We have analyzed peripheral blood from 47 chronically or previously HCV-infected patients for the presence of T lymphocytes and antibodies specific to the ARFP. Anti-ARFP antibodies were detected in 41.6% of the patients infected with various HCV genotypes. Using a specific ARFP 99-amino-acid polypeptide as well as four ARFP predicted class I-restricted 9-mer peptides, we show that 20% of the patients display specific lymphocytes capable of producing gamma interferon, interleukin-10, or both cytokines. Patients harboring three different viral genotypes (1a, 1b, and 3) carried T lymphocytes reactive to genotype 1b-derived peptides. In longitudinal analysis of patients receiving therapy, both core and ARFP-specific T-cell- and B-cell-mediated responses were documented. The magnitude and kinetics of the HCV antigen-specific responses differed and were not linked with viremia or therapy outcome. These observations provide strong and new arguments in favor of the synthesis, during natural HCV infection, of an ARFP derived from the core sequence. Moreover, the present data provide the first demonstration of the presence of T-cell-mediated immune responses directed to this novel HCV antigen.In vitro studies have described the synthesis of an alternative reading frame form of the hepatitis C virus (HCV) core protein that was named F protein or ARFP (alternative reading frame protein) and includes a domain coded by the +1 open reading frame of the RNA core coding region. The expression of this protein in HCV-infected patients remains controversial. We have analyzed peripheral blood from 47 chronically or previously HCV-infected patients for the presence of T lymphocytes and antibodies specific to the ARFP. Anti-ARFP antibodies were detected in 41.6% of the patients infected with various HCV genotypes. Using a specific ARFP 99-amino-acid polypeptide as well as four ARFP predicted class I-restricted 9-mer peptides, we show that 20% of the patients display specific lymphocytes capable of producing gamma interferon, interleukin-10, or both cytokines. Patients harboring three different viral genotypes (1a, 1b, and 3) carried T lymphocytes reactive to genotype 1b-derived peptides. In longitudinal analysis of patients receiving therapy, both core and ARFP-specific T-cell- and B-cell-mediated responses were documented. The magnitude and kinetics of the HCV antigen-specific responses differed and were not linked with viremia or therapy outcome. These observations provide strong and new arguments in favor of the synthesis, during natural HCV infection, of an ARFP derived from the core sequence. Moreover, the present data provide the first demonstration of the presence of T-cell-mediated immune responses directed to this novel HCV antigen. |
| Databáze: | OpenAIRE |
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