Deconvoluting the composition of low-frequency hepatitis C viral quasispecies: comparison of genotypes and NS3 resistance-associated variants between HCV/HIV coinfected hemophiliacs and HCV monoinfected patients in Japan

PloS One
Masato OgishiKazuhiko Koike

Abstract

Pre-existing low-frequency resistance-associated variants (RAVs) may jeopardize successful sustained virological responses (SVR) to HCV treatment with direct-acting antivirals (DAAs). However, the potential impact of low-frequency (∼0.1%) mutations, concatenated mutations (haplotypes), and their association with genotypes (Gts) on the treatment outcome has not yet been elucidated, most probably owing to the difficulty in detecting pre-existing minor haplotypes with sufficient length and accuracy. Herein, we characterize a methodological framework based on Illumina MiSeq next-generation sequencing (NGS) coupled with bioinformatics of quasispecies reconstruction (QSR) to realize highly accurate variant calling and genotype-haplotype detection. The core-to-NS3 protease coding sequences in 10 HCV monoinfected patients, 5 of whom had a history of blood transfusion, and 11 HCV/HIV coinfected patients with hemophilia, were studied. Simulation experiments showed that, for minor variants constituting more than 1%, our framework achieved a positive predictive value (PPV) of 100% and sensitivities of 91.7-100% for genotyping and 80.6% for RAV screening. Genotyping analysis indicated the prevalence of dominant Gt1a infection in coinfected ...Continue Reading

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Citations

Dec 24, 2015·Viruses·Asma Ahmed, Daniel J Felmlee
Sep 14, 2016·International Journal of Molecular Sciences·Nadia MarascioUNKNOWN The SINERGIE-UMG Study Group
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Nov 12, 2016·World Journal of Gastroenterology : WJG·Dimas Alexandre KliemannCharles Wood
May 8, 2021·World Journal of Hepatology·Geane Lopes FloresLivia Melo Villar

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Datasets Mentioned

BETA
D10749
DRA002750
AF01175
AB047639

Methods Mentioned

BETA
genotyping
PCR
in vitro transcription
CirSeq

Software Mentioned

Codon
MAFFT
CirSeq
R package deepSNV
FastTree
Linux
R
Geneious
QuRe
HCV Sequence Alignments

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