Dynamic evolution of hepatitis C virus resistance-associated substitutions in the absence of antiviral treatment

Resistance against new hepatitis C virus (HCV) antivirals is an area of increasing interest. Resistance-associated substitutions (RASs) have been identified in treatment-naïve individuals, but pressures driving treatment-independent RAS emergence are poorly understood. We analysed the longitudinal e...

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Bibliographic Details
Published in:Scientific reports 2017-01, Vol.7 (1), p.41719, Article 41719
Main Authors: Eltahla, Auda A., Leung, Preston, Pirozyan, Mehdi R., Rodrigo, Chaturaka, Grebely, Jason, Applegate, Tanya, Maher, Lisa, Luciani, Fabio, Lloyd, Andrew R., Bull, Rowena A.
Format: Article
Language:English
Subjects:
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Amino Acid Substitution
Antiviral agents
Antiviral Agents - pharmacology
CD8 antigen
Disease resistance
Drug Resistance, Viral
Epitopes
Evolution, Molecular
Genome, Viral
Genomes
Genotype
Hepacivirus - drug effects
Hepacivirus - genetics
Hepatitis
Hepatitis C
Hepatitis C - drug therapy
Hepatitis C - virology
Histocompatibility antigen HLA
Humanities and Social Sciences
Humans
Longitudinal Studies
Lymphocytes T
multidisciplinary
Mutation
Reproductive fitness
Science
Science (multidisciplinary)
T-Lymphocytes - metabolism
Viral Nonstructural Proteins - genetics
Whole Genome Sequencing
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Summary:Resistance against new hepatitis C virus (HCV) antivirals is an area of increasing interest. Resistance-associated substitutions (RASs) have been identified in treatment-naïve individuals, but pressures driving treatment-independent RAS emergence are poorly understood. We analysed the longitudinal evolution of RASs in twelve participants with early acute HCV infections. Full-genome deep sequences were analysed for changes in RAS frequency within NS3, NS5A and NS5B-coding regions over the course of the infection. Emergence of RASs relevant only to the polymerase non-nucleoside inhibitors (NNI) was detected, and these lay within CD8+ T-cell epitopes. Conversely, the loss of NNI RASs over time appeared likely to be driven by viral fitness constraints. These results highlight the importance of monitoring CD8+ T cell epitope-associated RASs in populations with dominant HLA types.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep41719