Selection-Driven Immune Escape Is Not A Significant Factor in the Failure of Cd4 T Cell Responses in Persistent Hepatitis C Virus Infection
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Le résumé fourni par la source
UNLABELLED: Immune escape driven by selection pressure from virus-specific CD8 T cells has been demonstrated in both chimpanzees and humans infected with the hepatitis C virus (HCV). Although escape mutations have also been characterized in major histocompatibility complex (MHC) class II-restricted HCV epitopes, it is unknown whether selection-driven immune escape by CD4 T cell epitopes is a significant factor in the failure of these responses or contributes to persistent infection. To address this issue, evolution of MHC class I- and class II-restricted HCV epitopes was compared in four chimpanzees persistently infected with the virus for more than 10 years. We identified an amino acid change in a CD4 epitope of the HCV NS3 protein in one of the chimpanzees 3 years after infection. This mutation resulted in diminished activation, cytokine production (interferon-gamma and interleukin-2), and proliferation by an epitope-specific CD4 T cell line. We expanded our analysis to determine if mutations were common in multiple CD4 versus CD8 T cell epitopes in the four chronically infected animals. Whereas we observed mutations in over 75% of CD8 T cell epitopes analyzed in this study, only 18% of CD4 T cell epitopes analyzed showed amino acid changes. The frequency of changes in class II epitopes was not different from flanking regions, so CD4 T cells rarely exert selection pressure against the HCV genome. CONCLUSION: Apparent mutational escape can occur in MHC class II-restricted epitopes, but this is uncommon when compared with class I-restricted epitopes in the same individual. This indicates that other mechanisms for silencing CD4 T cells are dominant in persistent HCV infections.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Selection-Driven Immune Escape Is Not A Significant Factor in the Failure of Cd4 T Cell Responses in Persistent Hepatitis C Virus Infection
- Date Crossref
- 01/02/2010
- Éditeur
- Ovid Technologies (Wolters Kluwer Health)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Nationwide Children's Hospital Center for Vaccines and Immunity pays non établi dans la noticeÉtablissement de santé
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University of Louisiana at Lafayette pays non établi dans la noticeUniversité ou école supérieure
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University of South Carolina Division of Biological Sciences pays non établi dans la noticeUniversité ou école supérieure
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The Ohio State University pays non établi dans la noticeUniversité ou école supérieure
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College of Medicine and Public Health pays non établi dans la noticeUniversité ou école supérieure
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fax: 614-722-3680 pays non établi dans la noticeInstitution
Center for Vaccines and Immunity — Nationwide Children's Hospital, University of Louisiana at Lafayette et Division of Biological Sciences — University of South Carolina, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.