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BukuHCV 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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