ArticlePloS one2011
Genetic heterogeneity of hepatitis C virus in association with antiviral therapy determined by ultra-deep sequencing.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 88 citations in OpenAlex.
- Evolution of hepatitis C virus quasispecies during repeated treatment with the NS3/4A protease inhibitor telaprevir.Antimicrobial agents and chemotherapy · 2015Trial
- Naturally occurring dominant drug resistance mutations occur infrequently in the setting of recently acquired hepatitis C.Antiviral therapy · 2015Trial
- Ultradeep sequencing study of chronic hepatitis C virus genotype 1 infection in patients treated with daclatasvir, peginterferon, and ribavirin.Antimicrobial agents and chemotherapy · 2014Trial
- Review
- Indels in SARS-CoV-2 occur at template-switching hotspots.BioData mining · 2021Article
- Using Next Generation Sequencing to Study the Genetic Diversity of Candidate Live Attenuated Zika Vaccines.Vaccines · 2020Article
- A machine learning-based treatment prediction model using whole genome variants of hepatitis C virus.PloS one · 2020Article
- Exploring the hepatitis C virus genome using single molecule real-time sequencing.World journal of gastroenterology · 2019Review
- Inter- and intra-lineage genetic diversity of wild-type Zika viruses reveals both common and distinctive nucleotide variants and clusters of genomic diversity.Emerging microbes & infections · 2019Article
- Seasonal Genetic Drift of Human Influenza A Virus Quasispecies Revealed by Deep Sequencing.Frontiers in microbiology · 2018Article
- Evolution of multi-drug resistant HCV clones from pre-existing resistant-associated variants during direct-acting antiviral therapy determined by third-generation sequencing.Scientific reports · 2017Article
- Novel functional hepatitis C virus glycoprotein isolates identified using an optimized viral pseudotype entry assay.The Journal of general virology · 2016Article
- Copy number variation of genes involved in the hepatitis C virus-human interactome.Scientific reports · 2016Article
- Different Variants in Reverse Transcriptase Domain Determined by Ultra-deep Sequencing in Treatment-naïve and Treated Indonesian Patients Infected with Hepatitis B Virus.The Kobe journal of medical sciences · 2016Article
- Pre-existence and Persistence of Resistant Minority Hepatitis C Virus Variants in Genotype 1-Infected Patients Treated With Simeprevir/Peginterferon/Ribavirin.Open forum infectious diseases · 2016Article
- Intrinsic Viral Factors Are the Dominant Determinants of the Hepatitis C Virus Response to Interferon Alpha Treatment in Chimeric Mice.PloS one · 2016Article
- Virologic Tools for HCV Drug Resistance Testing.Viruses · 2015Review
- Importance of virological response in the early stage of telaprevir-based triple therapy for hepatitis C.World journal of hepatology · 2015Article
- Review
- Deep sequencing and phylogenetic analysis of variants resistant to interferon-based protease inhibitor therapy in chronic hepatitis induced by genotype 1b hepatitis C virus.Journal of virology · 2015Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsThe hepatitis C virus (HCV) invariably shows wide heterogeneity in infected patients, referred to as a quasispecies population. Massive amounts of genetic information due to the abundance of HCV variants could be an obstacle to evaluate the viral genetic heterogeneity in detail.
methodsUsing a newly developed massive-parallel ultra-deep sequencing technique, we investigated the viral genetic heterogeneity in 27 chronic hepatitis C patients receiving peg-interferon (IFN) α2b plus ribavirin therapy.
resultsUltra-deep sequencing determined a total of more than 10 million nucleotides of the HCV genome, corresponding to a mean of more than 1000 clones in each specimen, and unveiled extremely high genetic heterogeneity in the genotype 1b HCV population. There was no significant difference in the level of viral complexity between immediate virologic responders and non-responders at baseline (p = 0.39). Immediate virologic responders (n = 8) showed a significant reduction in the genetic complexity spanning all the viral genetic regions at the early phase of IFN administration (p = 0.037). In contrast, non-virologic responders (n = 8) showed no significant changes in the level of viral quasispecies (p = 0.12), indicating that very few viral clones are sensitive to IFN treatment. We also demonstrated that clones resistant to direct-acting antivirals for HCV, such as viral protease and polymerase inhibitors, preexist with various abundances in all 27 treatment-naïve patients, suggesting the risk of the development of drug resistance against these agents.
conclusionUse of the ultra-deep sequencing technology revealed massive genetic heterogeneity of HCV, which has important implications regarding the treatment response and outcome of antiviral therapy.
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