HCV genotype-3a T cell immunity: specificity, function and impact of therapy.

Humphreys, I; von Delft, A; Brown, A; Hibbert, L; Collier, J; Foster, G; Rahman, M; Christian, A; Klenerman, P; Barnes, E

Journal article

HCV genotype-3a T cell immunity: specificity, function and impact of therapy.

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)-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.

Publication status:: Published

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Share
Cite

Cite this record

APA Style

Humphreys, I., von Delft, A., Brown, A., Hibbert, L., Collier, J., Foster, G., Rahman, M., Christian, A., Klenerman, P., & Barnes, E. (2012). HCV genotype-3a T cell immunity: specificity, function and impact of therapy. Gut, 61(11), 1589–1599.

MLA Style

Humphreys, I, et al. “HCV Genotype-3a T Cell Immunity: Specificity, Function and Impact of Therapy.” Gut, vol. 61, no. 11, 2012, pp. 1589–99.

Chicago Style

Humphreys, I, A von Delft, A Brown, et al. 2012. “HCV Genotype-3a T Cell Immunity: Specificity, Function and Impact of Therapy.” Gut 61 (11): 1589–99.
Print