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Master Thesis

Dynamique de l’évolution intra-patient du VHC par NGS

Abstract : High throughput sequencing of rapidly evolving hepatitis C virus populations enables large-scale studies of within-host viral heterogeneity and resistance to antiviral treatment regimes that are commonly observed in clinical cases with chronic infections. While escape from direct antiviral drugs can be explained by resistance mutations in targeted genomic regions, the absence of response to dual therapies has remained less understood. In this study we implemented amplicon sequencing to survey genomic variation at the Core and NS5B regions of HCV over a period of 13 years for two patients followed for chronic hepatitis C at Grenoble-Alpes University Hospital. From samples obtained at several time points, we observed mixed infection by multiple HCV genotypes in patients. Genetic heterogeneity and sample composition analysis provided information about the changes in viral population over the course of clinical treatment, with NS5B experiencing a sharp increase in diversity after treatment initiation compared to baseline. Evidence for HCV population genetic structure was observed in each patient, occurring in divergent lineages in phylogenetic trees. These observations point towards diversifying selection occurring post-treatment, acting on standing genomic variation and maintaining high genetic heterogeneity during infection. Being associated with treatment efficiency, the results provide the first evidence for antiviral treatment inducing soft selective sweeps in chronically infected patients with multiple HCV genotypes.
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Master Thesis
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Submitted on : Thursday, October 26, 2017 - 11:27:02 AM
Last modification on : Wednesday, July 15, 2020 - 8:58:04 AM
Long-term archiving on: : Saturday, January 27, 2018 - 1:25:34 PM


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  • HAL Id : dumas-01624390, version 1


Alban Caporossi. Dynamique de l’évolution intra-patient du VHC par NGS. Médecine humaine et pathologie. 2017. ⟨dumas-01624390⟩



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