PT  - JOURNAL ARTICLE
AU  - Humphreys, Isla S
AU  - von Delft, Annette
AU  - Brown, Anthony
AU  - Hibbert, Linda
AU  - Collier, Jane D
AU  - Foster, Graham R
AU  - Rahman, Monira
AU  - Christian, Annabel
AU  - Klenerman, Paul
AU  - Barnes, Eleanor
TI  - HCV genotype-3a T cell immunity: specificity, function and impact of therapy
AID  - 10.1136/gutjnl-2011-300650
DP  - 2012 Nov 01
TA  - Gut
PG  - 1589--1599
VI  - 61
IP  - 11
4099  - http://gut.bmj.com/content/61/11/1589.short
4100  - http://gut.bmj.com/content/61/11/1589.full
SO  - Gut2012 Nov 01; 61
AB  - 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)-α/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 n=85) using specific peptide panels in IFN-γ 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 (p=0.0183). 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.