Research Article

A Bioinformatics Pipeline for the Analyses of Viral Escape Dynamics and Host Immune Responses during an Infection

Figure 3

A representative example of the output of the pipeline applied on longitudinally collected viral sequences and immune responses data from a patient chronically infected with HCV. (a) The same viral dynamics plot carried over from Figure 2. (b) The experimental results from ELISPOT detailing the measurement of two HCV specific CD8+ T-cell responses targeting epitopes 1602RAQAPPPSW1610 (green) and 1633RLGPVQNEV1641 (pink). Immune responses are first detected at around 50 DPI at low amount. These responses then increase in magnitude at 80–100 DPI and then decline over the course of the infection. (c–f) Circos plots representing the partial NS3 region (amino acid region 1200–1800) in Ch_240 that contain the two epitopes targeted by the CD8+ T-cell responses in (b). The red histogram around the circle shows the frequency of occurrence of nonsynonymous mutations with a scale from 0% to 100% at that site. These two CD8+ T-Cell epitopes 1602RAQAPPPSW1610 (green trapezium) and 1633RLGPVQNEV1641 (pink trapezium) are also represented. Fixation events (mutations at frequency >90%) are represented with # in (e) and (f). The arcs shown in the inner circular area represent statistically significant cooccurring pairs of mutations that are shared by two or more viral variants. The asterisk ( ) in (e) denotes the potential compensatory mutation at position G1671R cooccurring with immune escape variants identified within 1602RAQAPPPSW1610 (green).
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