ArticleAntimicrobial agents and chemotherapy2016
Enhancement of the Replication of Hepatitis C Virus Replicons of Genotypes 1 to 4 by Manipulation of CpG and UpA Dinucleotide Frequencies and Use of Cell Lines Expressing SECL14L2 for Antiviral Resistance Testing.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 35 citations in OpenAlex.
- Development of a Norway rat hepacivirus reporter for high-throughput quantification of neutralizing antibodies.Journal of virology · 2026Article
- Predicting host tropism in influenza a viruses: insights from multi-segment nucleotide signatures.Journal of translational medicine · 2025Article
- Adapted hepatitis C virus clone infects innate immunity-deficient mouse hepatocytes with minimal human HCV entry factors.JHEP reports : innovation in hepatology · 2025Article
- Machine learning methods for predicting human-adaptive influenza A virus reassortment based on intersegment constraint.Frontiers in microbiology · 2025Article
- General Intelligence Framework to Predict Virus Adaptation Based on a Genome Language Model.Research (Washington, D.C.) · 2025Article
- Dengue virus preferentially uses human and mosquito non-optimal codons.Molecular systems biology · 2024Article
- Functional characterization of 5' untranslated region (UTR) secondary RNA structures in the replication of tick-borne encephalitis virus in mammalian cells.PLoS neglected tropical diseases · 2023Article
- Identification of Host Factors Differentially Induced by Clinically Diverse Strains of Tick-Borne Encephalitis Virus.Journal of virology · 2022Article
- Compositional biases in RNA viruses: Causes, consequences and applications.Wiley interdisciplinary reviews. RNA · 2022Review
- The dinucleotide composition of the Zika virus genome is shaped by conflicting evolutionary pressures in mammalian hosts and mosquito vectors.PLoS biology · 2021Article
- Comparative Analysis of Within-Host Mutation Patterns and Diversity of Hepatitis C Virus Subtypes 1a, 1b, and 3a.Viruses · 2021Article
- A novel substitution in NS5A enhances the resistance of hepatitis C virus genotype 3 to daclatasvir.The Journal of general virology · 2021Article
- Insights into the unique characteristics of hepatitis C virus genotype 3 revealed by development of a robust sub-genomic DBN3a replicon.The Journal of general virology · 2020Article
- Synonymous Dinucleotide Usage: A Codon-Aware Metric for Quantifying Dinucleotide Representation in Viruses.Viruses · 2020Article
- Machine Learning Methods for Predicting Human-Adaptive Influenza A Viruses Based on Viral Nucleotide Compositions.Molecular biology and evolution · 2020Article
- Phenotypic analysis of mutations at residue 146 provides insights into the relationship between NS5A hyperphosphorylation and hepatitis C virus genome replication.The Journal of general virology · 2020Article
- Structure-function analysis of the equine hepacivirus 5' untranslated region highlights the conservation of translational mechanisms across the hepaciviruses.The Journal of general virology · 2019Article
- Replicons of a Rodent Hepatitis C Model Virus Permit Selection of Highly Permissive Cells.Journal of virology · 2019Article
- The role of ZAP and OAS3/RNAseL pathways in the attenuation of an RNA virus with elevated frequencies of CpG and UpA dinucleotides.Nucleic acids research · 2019Article
- Resistance analysis of genotype 3 hepatitis C virus indicates subtypes inherently resistant to nonstructural protein 5A inhibitors.Hepatology (Baltimore, Md.) · 2019Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Treatment for hepatitis C virus (HCV) has improved greatly through the use of direct-acting antivirals (DAAs). However, their effectiveness and potential for drug resistance development in non-genotype 1 variants of HCV remain relatively unexplored, as in vitro assays to assess drug susceptibility are poorly developed and unsuited for a transient-transfection format. In the current study, we have evaluated the effects of dinucleotide frequency changes in the replicon and the use of a SEC14L2-expressing cell line on the replication of HCVs of different genotypes and evaluated the resulting assay formats for measurements of susceptibility to the DAA sofosbuvir. Removal of CpG and UpA dinucleotides from the luciferase gene used in HCV replicons of genotype 1b (Con1) and genotype 2a (JFH-1) achieved between 10- and 100-fold enhancement of replication over that of the wild type posttransfection. Removal of CpG and UpA dinucleotides in the neomycin gene or deletion of the whole gene in replicons of genotype 3a (S52) and genotype 4a (ED43) enhanced replication, but phenotypic effects on altering luciferase gene composition were minimal. A further 10-fold replication enhancement of replicons from all four genotypes was achieved by using a transgenic Huh7.5 cell line expressing SECL14L2, whose expression showed a dose-dependent effect on HCV replication that was reversible by small interfering RNA (siRNA) knockdown of gene expression. By combining these strategies, the 100- to 1,000-fold enhancement of replication allowed the susceptibility of all four genotypes to the RNA polymerase inhibitor sofosbuvir to be robustly determined in a transient-transfection assay format. These methods of replication enhancement provide new tools for monitoring the susceptibility and resistance of a wide range of HCV genotypes to DAAs.
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