HCV genotype-3a T cell immunity: specificity, function and impact of therapy.
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 i...
| Egile Nagusiak: | , , , , , , , , , |
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| Formatua: | Journal article |
| Hizkuntza: | English |
| Argitaratua: |
2012
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| _version_ | 1826302952425390080 |
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| author | Humphreys, I von Delft, A Brown, A Hibbert, L Collier, J Foster, G Rahman, M Christian, A Klenerman, P Barnes, E |
| author_facet | Humphreys, I von Delft, A Brown, A Hibbert, L Collier, J Foster, G Rahman, M Christian, A Klenerman, P Barnes, E |
| author_sort | Humphreys, I |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T05:55:15Z |
| format | Journal article |
| id | oxford-uuid:ea4a956c-800a-4d68-b3b8-72c5cb26a31c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:55:15Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:ea4a956c-800a-4d68-b3b8-72c5cb26a31c2022-03-27T11:00:56ZHCV genotype-3a T cell immunity: specificity, function and impact of therapy.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ea4a956c-800a-4d68-b3b8-72c5cb26a31cEnglishSymplectic Elements at Oxford2012Humphreys, Ivon Delft, ABrown, AHibbert, LCollier, JFoster, GRahman, MChristian, AKlenerman, PBarnes, EBACKGROUND: 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. |
| spellingShingle | Humphreys, I von Delft, A Brown, A Hibbert, L Collier, J Foster, G Rahman, M Christian, A Klenerman, P Barnes, E HCV genotype-3a T cell immunity: specificity, function and impact of therapy. |
| title | HCV genotype-3a T cell immunity: specificity, function and impact of therapy. |
| title_full | HCV genotype-3a T cell immunity: specificity, function and impact of therapy. |
| title_fullStr | HCV genotype-3a T cell immunity: specificity, function and impact of therapy. |
| title_full_unstemmed | HCV genotype-3a T cell immunity: specificity, function and impact of therapy. |
| title_short | HCV genotype-3a T cell immunity: specificity, function and impact of therapy. |
| title_sort | hcv genotype 3a t cell immunity specificity function and impact of therapy |
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