ArticleViruses2015
Genetic Diversity and Selective Pressure in Hepatitis C Virus Genotypes 1-6: Significance for Direct-Acting Antiviral Treatment and Drug Resistance.
Article in Viruses, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 66 citations in OpenAlex.
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- HCV immunodominant peptide mapping reveals unique HLA-A*02-restricted signatures: insights for CD8Immunogenetics · 2025Article
- An Increase in the Prevalence of Clinically Relevant Resistance-Associated Substitutions in Four Direct-Acting Antiviral Regimens: A Study Using GenBank HCV Sequences.Pathogens (Basel, Switzerland) · 2024Article
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- First report on molecular docking analysis and drug resistance substitutions to approved HCV NS5A and NS5B inhibitors amongst Iranian patients.BMC gastroenterology · 2021Article
- Structural perspectives on HCV humoral immune evasion mechanisms.Current opinion in virology · 2021Review
- Phylogenetic and Molecular Analyses of More Prevalent HCV1b Subtype in the Calabria Region, Southern Italy.Journal of clinical medicine · 2021Article
- Direct-acting Antiviral in the Treatment of Chronic Hepatitis C: Bonuses and Challenges.International journal of medical sciences · 2020Review
- Danoprevir for the Treatment of Hepatitis C Virus Infection: Design, Development, and Place in Therapy.Drug design, development and therapy · 2020Review
- An Evolutionary Model-Based Approach To Quantify the Genetic Barrier to Drug Resistance in Fast-Evolving Viruses and Its Application to HIV-1 Subtypes and Integrase Inhibitors.Antimicrobial agents and chemotherapy · 2019Article
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- Field evaluation of GeneXpertJournal of viral hepatitis · 2019Article
- Structural and Epitope Analysis (T- and B-Cell Epitopes) of Hepatitis C Virus (HCV) Glycoproteins: AnJournal of clinical and experimental hepatology · 2018Article
- Fast estimation of genetic relatedness between members of heterogeneous populations of closely related genomic variants.BMC bioinformatics · 2018Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Treatment with pan-genotypic direct-acting antivirals, targeting different viral proteins, is the best option for clearing hepatitis C virus (HCV) infection in chronically infected patients. However, the diversity of the HCV genome is a major obstacle for the development of antiviral drugs, vaccines, and genotyping assays. In this large-scale analysis, genome-wide diversity and selective pressure was mapped, focusing on positions important for treatment, drug resistance, and resistance testing. A dataset of 1415 full-genome sequences, including genotypes 1-6 from the Los Alamos database, was analyzed. In 44% of all full-genome positions, the consensus amino acid was different for at least one genotype. Focusing on positions sharing the same consensus amino acid in all genotypes revealed that only 15% was defined as pan-genotypic highly conserved (≥99% amino acid identity) and an additional 24% as pan-genotypic conserved (≥95%). Despite its large genetic diversity, across all genotypes, codon positions were rarely identified to be positively selected (0.23%-0.46%) and predominantly found to be under negative selective pressure, suggesting mainly neutral evolution. For NS3, NS5A, and NS5B, respectively, 40% (6/15), 33% (3/9), and 14% (2/14) of the resistance-related positions harbored as consensus the amino acid variant related to resistance, potentially impeding treatment. For example, the NS3 variant 80K, conferring resistance to simeprevir used for treatment of HCV1 infected patients, was present in 39.3% of the HCV1a strains and 0.25% of HCV1b strains. Both NS5A variants 28M and 30S, known to be associated with resistance to the pan-genotypic drug daclatasvir, were found in a significant proportion of HCV4 strains (10.7%). NS5B variant 556G, known to confer resistance to non-nucleoside inhibitor dasabuvir, was observed in 8.4% of the HCV1b strains. Given the large HCV genetic diversity, sequencing efforts for resistance testing purposes may need to be genotype-specific or geographically tailored.
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