Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Schulze Zur Wiesch, J
MetadataShow full item record
AbstractIn the setting of acute hepatitis C virus (HCV) infection, robust HCV-specific CD8+ cytotoxic T lymphocyte (CTL) responses are associated with initial control of viremia. Despite these responses, 70-80% of individuals develop persistent infection. Although viral escape from CD8 responses has been illustrated in the chimpanzee model of HCV infection, the effect of CD8 selection pressure on viral evolution and containment in acute HCV infection in humans remains unclear. Here, we examined viral evolution in an immunodominant human histocompatibility leukocyte antigen (HLA)-B8-restricted NS3 epitope in subjects with acute HCV infection. Development of mutations within the epitope coincided with loss of strong ex vivo tetramer and interferon γ enzyme-linked immunospot responses, and endogenous expression of variant NS3 sequences suggested that the selected mutations altered processing and presentation of the variant epitope. Analysis of NS3 sequences from 30 additional chronic HCV-infected subjects revealed a strong association between sequence variation within this region and expression of HLA-B8, supporting reproducible allele-specific selection pressures at the population level. Interestingly, transmission of an HLA-B8-associated escape mutation to an HLA-B8 negative subject resulted in rapid reversion of the mutation. Together, these data indicate that viral escape from CD8+ T cell responses occurs during human HCV infection and that acute immune selection pressure is of sufficient magnitude to influence HCV evolution.
PublisherRockefeller University Press
JournalJournal of Experimental Medicine
PubMed ID15611288 (pubmed)
Description© 2004 The Authors. Published by Rockefeller University Press. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1084/jem.20041006
SponsorsJ. Timm and G.M. Lauer were funded by the Deutsche Forschungs Gemeinschaft (DFG TI-323/1-1 and DFG LA 1241/1-1). M. Lucas is funded by the EU (QLK2-CT-2002-01329), and P. Klenerman is funded by the Wellcome Trust. This work was funded by the National Institutes of Health (AI31563), the Doris Duke Charitable Foundation, and the Howard Hughes Medical Institute.
Except where otherwise noted, this item's license is described as Licence for published version: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International
- CD8 epitope escape and reversion in acute HCV infection.
- Authors: Timm J, Lauer GM, Kavanagh DG, Sheridan I, Kim AY, Lucas M, Pillay T, Ouchi K, Reyor LL, Schulze zur Wiesch J, Gandhi RT, Chung RT, Bhardwaj N, Klenerman P, Walker BD, Allen TM
- Issue date: 2004 Dec 20
- Distinct Escape Pathway by Hepatitis C Virus Genotype 1a from a Dominant CD8+ T Cell Response by Selection of Altered Epitope Processing.
- Authors: Walker A, Skibbe K, Steinmann E, Pfaender S, Kuntzen T, Megger DA, Groten S, Sitek B, Lauer GM, Kim AY, Pietschmann T, Allen TM, Timm J
- Issue date: 2016 Jan 1
- Escape from a dominant HLA-B*15-restricted CD8+ T cell response against hepatitis C virus requires compensatory mutations outside the epitope.
- Authors: Ruhl M, Chhatwal P, Strathmann H, Kuntzen T, Bankwitz D, Skibbe K, Walker A, Heinemann FM, Horn PA, Allen TM, Hoffmann D, Pietschmann T, Timm J
- Issue date: 2012 Jan
- Genetic variability of hepatitis C virus non-structural protein 3 and virus-specific CD8+ response in patients with chronic hepatitis C.
- Authors: López-Labrador FX, He XS, Berenguer M, Cheung RC, González-Candelas F, Wright TL, Greenberg HB
- Issue date: 2004 Apr