Positive selection of cytotoxic T lymphocyte escape variants during acute hepatitis C virus infection
| Autor: | Enea Spada, Silvia Guglietta, Lionello Ruggeri, Alfonso Mele, Luca Laurenti, Alessandra Vitelli, Gloria Taliani, Maria Rosaria Capobianchi, Enza Piccolella, Paola Del Porto, Cristiano Scottà, Alfredo Nicosia, Valentina Pacciani, Anna Rosa Garbuglia, Antonella Folgori, Maria Paola Perrone |
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| Přispěvatelé: | S., Guglietta, A. R., Garbuglia, V., Pacciani, C., Scotta, M. P., Perrone, L., Laurenti, E., Spada, A., Mele, M. R., Capobianchi, G., Taliani, A., Folgori, A., Vitelli, L., Ruggeri, Nicosia, Alfredo, E., Piccolella, P. D., Porto |
| Rok vydání: | 2005 |
| Předmět: |
MECHANISM
Adult Male CLEARANCE EPITOPES T cell Immunology Molecular Sequence Data Epitopes T-Lymphocyte Hepacivirus CD8-Positive T-Lymphocytes Viral Nonstructural Proteins Virus Replication Virus Epitope Evolution Molecular Interferon-gamma Immune system MHC class I medicine Immunology and Allergy Cytotoxic T cell Humans Amino Acid Sequence ACUTE HCV INFECTION biology IMMUNE-RESPONSES Immunodominant Epitopes Sequence Analysis DNA Cytotoxicity Tests Immunologic VIRAL ESCAPE Virology Hepatitis C Peptide Fragments PCR medicine.anatomical_structure Viral replication biology.protein Sequence Alignment CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | European journal of immunology. 35(9) |
| ISSN: | 0014-2980 |
| Popis: | Cellular immune responses are induced during hepatitis C virus (HCV) infection and acute-phase CD8(+) T cells are supposed to play an important role in controlling viral replication. In chimpanzees, failure of CD8(+) T cells to control HCV replication has been associated with acquisition of mutations in MHC class I-restricted epitopes. In humans, although selection of escape mutations in an immunodominant CTL epitope has been recently described, the overall impact of immune escape during acute HCV infection is unclear. Here, by performing an in depth analysis of the relationship between early cellular immune responses and viral evolution in a chronically evolving HCV acutely infected individual, we demonstrate: (i) the presence of a potent and focused CD8(+) T cell response against a novel epitope in the NS3 protein, (ii) the elimination of the quasi-species harboring the original amino acid sequence within this epitope, and (iii) the selection for a virus population bearing amino acid changes at a single residue within the cytotoxic T cell epitope that strongly diminished T cell recognition. These results support the view that acute-phase CD8(+) T cell responses exert a biologically relevant pressure on HCV replication and that viruses escaping this host response could have a significant survival advantage. |
| Databáze: | OpenAIRE |
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