Transmission of Clonal Hepatitis C Virus Genomes Reveals the Dominant but Transitory Role of CD8+T Cells in Early Viral Evolution
Rattachement africain : us, dk. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
The RNA genome of the hepatitis C virus (HCV) diversifies rapidly during the acute phase of infection, but the selective forces that drive this process remain poorly defined. Here we examined whether Darwinian selection pressure imposed by CD8(+) T cells is a dominant force driving early amino acid replacement in HCV viral populations. This question was addressed in two chimpanzees followed for 8 to 10 years after infection with a well-defined inoculum composed of a clonal genotype 1a (isolate H77C) HCV genome. Detailed characterization of CD8(+) T cell responses combined with sequencing of recovered virus at frequent intervals revealed that most acute-phase nonsynonymous mutations were clustered in class I epitopes and appeared much earlier than those in the remainder of the HCV genome. Moreover, the ratio of nonsynonymous to synonymous mutations, a measure of positive selection pressure, was increased 50-fold in class I epitopes compared with the rest of the HCV genome. Finally, some mutation of the clonal H77C genome toward a genotype 1a consensus sequence considered most fit for replication was observed during the acute phase of infection, but the majority of these amino acid substitutions occurred slowly over several years of chronic infection. Together these observations indicate that during acute hepatitis C, virus evolution was driven primarily by positive selection pressure exerted by CD8(+) T cells. This influence of immune pressure on viral evolution appears to subside as chronic infection is established and genetic drift becomes the dominant evolutionary force.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- Transmission of Clonal Hepatitis C Virus Genomes Reveals the Dominant but Transitory Role of CD8<sup>+</sup>T Cells in Early Viral Evolution
- Date Crossref
- 15/11/2011
- Éditeur
- American Society for Microbiology
- 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 pays non établi dans la noticeÉtablissement de santé
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University of Copenhagen pays non établi dans la noticeUniversité ou école supérieure
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National Institutes of Health pays non établi dans la noticeOrganisme public
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Copenhagen University Hospital Department of Infectious Diseases and Clinical Research Centre pays non établi dans la noticeÉtablissement de santé
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National Institute of Allergy and Infectious Diseases pays non établi dans la noticeStructure de recherche
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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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Ohio State University The Research Institute at Nationwide Children's Hospital pays non établi dans la noticeUniversité ou école supérieure
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Laboratory of Infectious Diseases Hepatitis Viruses Section pays non établi dans la noticeStructure de recherche
Nationwide Children's Hospital, University of Copenhagen et National Institutes of Health, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.