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Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Transmission of clonal hepatitis C virus genomes reveals the dominant but transitory role of CD8⁺ T cells in early viral evolution

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. CO-HEP; Copenhagen Hepatitis C Program

    Projekt: Typer af projekter

  1. Replicons of a rodent hepatitis C model virus permit selection of highly permissive cells

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. IDENTIFICATION OF PIPERAZINYLBENZENESULFONAMIDES AS NEW INHIBITORS OF CLAUDIN-1 TRAFFICKING AND HEPATITIS C VIRUS ENTRY

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Development of a downstream process for the production of an inactivated whole hepatitis C virus vaccine

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Global and local envelope protein dynamics of hepatitis C virus determine broad antibody sensitivity

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. An alternate conformation of HCV E2 neutralizing face as an additional vaccine target

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Benoît Callendret
  • Jens Bukh
  • Heather B Eccleston
  • Ryan Heksch
  • Dana L Hasselschwert
  • Robert H Purcell
  • Austin L Hughes
  • Christopher M Walker
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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.
OriginalsprogEngelsk
TidsskriftJournal of Virology
Vol/bind85
Udgave nummer22
Sider (fra-til)11833-45
Antal sider13
ISSN0022-538X
DOI
StatusUdgivet - nov. 2011

ID: 33107075