Distinct Escape Pathway by Hepatitis C Virus Genotype 1a from a Dominant CD8+ T Cell Response by Selection of Altered Epitope Processing.
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
Megger, Dominik A
Lauer, Georg M
Kim, Arthur Y
Allen, Todd M
MetadataShow full item record
AbstractAntiviral CD8(+) T cells are a key component of the adaptive immune response against HCV, but their impact on viral control is influenced by preexisting viral variants in important target epitopes and the development of viral escape mutations. Immunodominant epitopes highly conserved across genotypes therefore are attractive for T cell based prophylactic vaccines. Here, we characterized the CD8(+) T cell response against the highly conserved HLA-B*51-restricted epitope IPFYGKAI1373-1380 located in the helicase domain of NS3 in people who inject drugs (PWID) exposed predominantly to HCV genotypes 1a and 3a. Despite this epitope being conserved in both genotypes, the corresponding CD8(+) T cell response was detected only in PWID infected with genotype 3a and HCV-RNA negative PWID, but not in PWID infected with genotype 1a. In genotype 3a, the detection of strong CD8(+) T cell responses was associated with epitope variants in the autologous virus consistent with immune escape. Analysis of viral sequences from multiple cohorts confirmed HLA-B*51-associated escape mutations inside the epitope in genotype 3a, but not in genotype 1a. Here, a distinct substitution in the N-terminal flanking region located 5 residues upstream of the epitope (S1368P; P = 0.00002) was selected in HLA-B*51-positive individuals. Functional assays revealed that the S1368P substitution impaired recognition of target cells presenting the endogenously processed epitope. The results highlight that, despite an epitope being highly conserved between two genotypes, there are major differences in the selected viral escape pathways and the corresponding T cell responses.
CitationDistinct Escape Pathway by Hepatitis C Virus Genotype 1a from a Dominant CD8+ T Cell Response by Selection of Altered Epitope Processing. 2015, 90 (1):33-42 J. Virol.
AffiliationTWINCORE Centre for Experimental and Clinical Infection Research, Feodor-Lynen-Str. 7, 30625, Hannover, Germany.
JournalJournal of virology
The following license files are associated with this item:
- 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
- Impact of sequence variation in a dominant HLA-A*02-restricted epitope in hepatitis C virus on priming and cross-reactivity of CD8+ T cells.
- Authors: Ziegler S, Skibbe K, Walker A, Ke X, Heinemann FM, Heinold A, Mok JY, van Esch WJ, Yang D, Wölfl M, Timm J
- Issue date: 2014 Oct
- 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
- Protective effect of human leukocyte antigen B27 in hepatitis C virus infection requires the presence of a genotype-specific immunodominant CD8+ T-cell epitope.
- Authors: Neumann-Haefelin C, Timm J, Schmidt J, Kersting N, Fitzmaurice K, Oniangue-Ndza C, Kemper MN, Humphreys I, McKiernan S, Kelleher D, Lohmann V, Bowness P, Huzly D, Rosen HR, Kim AY, Lauer GM, Allen TM, Barnes E, Roggendorf M, Blum HE, Thimme R
- Issue date: 2010 Jan
- Escape from HLA-B*08-restricted CD8 T cells by hepatitis C virus is associated with fitness costs.
- Authors: Salloum S, Oniangue-Ndza C, Neumann-Haefelin C, Hudson L, Giugliano S, aus dem Siepen M, Nattermann J, Spengler U, Lauer GM, Wiese M, Klenerman P, Bright H, Scherbaum N, Thimme R, Roggendorf M, Viazov S, Timm J
- Issue date: 2008 Dec