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HCV genotype-3a T cell immunity: specificity, function and impact of therapy (from Gut, 2012, 61, 1589-1599)
Bibliografi
Author:
Humphreys, Isla S.
;
Delft, Annette von
;
Brown, Anthony
;
Hibbert, Linda
;
Collier, Jane D.
;
Foster, Graham R.
;
Rahman, Monira
;
Christian, Annabel
;
Klenerman, Paul
;
Barnes, Eleanor
Topik:
HCV
;
Theraphy
;
Validation ref - 31
Bahasa:
(EN )
Tahun Terbit:
2012
Jenis:
Article - diterbitkan di jurnal ilmiah internasional
Fulltext:
gutjnl-2011-300650.pdf
(714.79KB;
0 download
)
Abstract
Background: Hepatitis C virus (HCV) genotype-3a infection is now the dominant strain in South Asia and the UK. Characteristic features include a favourable response to therapy; the reasons for this are unknown but may include distinct genotype-3a-specific T cell immunity. In contrast to genotype-1 infection, T cell immunity to this subtype is poorly defined.
Objectives: The aims of the study were to (1) define the frequency, specificity and cross-reactivity of T cell immunity across the whole viral genome in genotype-3a infection and (2) assess the impact of interferon (IFN)-a/ribavirin on T cell immunity.
Design: T cell responses in chronic and resolved HCV genotype-3a were analysed in comparison with genotype-1 infection (total n¼85) using specific peptide panels in IFN-g ELISpot assays. T cell responses were followed longitudinally in a subset of genotype-3a infected patients receiving therapy. Responses were further defined by CD4 and CD8 subset analysis, sequencing of autologous virus and cross-reactivity of genotype-3a with genotype-1a/-1b antigens.
Results: CD8 T cell responses commonly targeted the non-structural (NS) proteins in chronic genotype-3a infection whereas in genotype-1 infection CD4 responses targeting HCV core predominated (p¼0.0183). Resolved infection was associated with CD4 T cells targeting NS proteins. Paradoxically, a sustained response to therapy was associated with a brisk decline in virus-specific and total lymphocyte counts that recovered after treatment.
Conclusion: HCV genotype-3a exhibits a distinct T cell specificity with implications for vaccine design. However, our data do not support the theory that genotype-3a viral clearance with therapy is associated with an enhanced antiviral T cell response. Paradoxically, a reduction in these responses may serve as a biomarker of IFN responsiveness.
[validation ref - 31]
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