Fig. 1: Comprehensive functional and multi-omics analyses show early and functional HCV-specific CD8+ T cells associated with viral immune escape.
a Experimental design and details on the longitudinal study cohort utilised in this study (created with biorender.com). b Swimming plot outlining individuals (N = 17) followed longitudinally from early-phase of infection and in both disease outcomes. Sample viremia and the total number of epitopes detected are shown. c Comparison of viral loads by phase of infection (early: ≤120 DPI, late: >120 DPI) and disease outcome (two-sided Wilcoxon signed-rank test). Data are presented as box plots showing the median and 75% quantile. N = 147 biologically independent measures were used. Group comparison tests were performed utilising. d Comparison of viral genome diversity measured as Shannon entropy across disease outcomes in the early (≤120 DPI) phase of infection, group comparison tests were performed utilising two-sided Wilcoxon signed-rank test. Box plots show median and 75% quantile (N = 56 sample time points). e Comparison of IFN-γ responses according to the sample timepoint and disease outcome (two-sided Mann-Whitney test). N = 148 independent measures from each unique individual, epitope, and timepoint combination. Shown are the median and 95% confidence interval. f Comparison of IFN-γ responses in chronic progressors (N = 7 individuals, N = 99 biologically independent measures) divided by epitopes that undergo immune escape or remain conserved during the infection. Shown are the median and 95% confidence interval. Comparisons were performed using two-sided Mann-Whitney test. g IFN-γ ELISpot values for samples from each epitope-specific immune response. Data are presented with box plots showing as median and 75%, n = 154 biologically independent measures were used. h Estimate of the rate of immune escape (continuous line showing model fit) and kinetics of IFN-γ response (SFU values), connected with dashed lines. i Correlation between the estimated rates of immune escape for each identified epitope and the corresponding maximum IFN-γ ELISpot responses measured within the first 120 DPI. All measures were obtained from chronic progressors. Data were fitted with a linear regression model, and R2 and p value are reported.
