Positive selection of cytotoxic T lymphocytes escape variants during acute hepatitis C virus infection

Silvia Guglietta, Anna Rosa Garbuglia, Valentina Pacciani, Cristiano Scottà, Maria Paola Perrone, Luca Laurenti, Enea Spada, Alfonso Mele, Maria Rosaria Capobianchi, Gloria Taliani, Antonella Folgori, Alessandra Vitelli, Lionello Ruggeri, Alfredo Nicosia, Enza Piccolella, Paola Del Porto

Research output: Contribution to journalArticle

Abstract

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 quasispecies 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.

Original languageEnglish
Pages (from-to)2627-2637
Number of pages11
JournalEuropean Journal of Immunology
Volume35
Issue number9
DOIs
Publication statusPublished - Sep 2005

Keywords

  • CD8 T lymphocytes
  • HCV
  • Viral escape

ASJC Scopus subject areas

  • Immunology

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  • Cite this

    Guglietta, S., Garbuglia, A. R., Pacciani, V., Scottà, C., Perrone, M. P., Laurenti, L., Spada, E., Mele, A., Capobianchi, M. R., Taliani, G., Folgori, A., Vitelli, A., Ruggeri, L., Nicosia, A., Piccolella, E., & Del Porto, P. (2005). Positive selection of cytotoxic T lymphocytes escape variants during acute hepatitis C virus infection. European Journal of Immunology, 35(9), 2627-2637. https://doi.org/10.1002/eji.200526067