ArticleProceedings of the National Academy of Sciences of the United States of America2011
Contribution of a mutational bias in hepatitis C virus replication to the genetic barrier in the development of drug resistance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
71 citing papers in PubMed, 140 citations in OpenAlex.
- Elucidation of hepatitis C virus transmission and early diversification by single genome sequencing.PLoS pathogens · 2012Trial
- Quantifying the diversification of hepatitis C virus (HCV) during primary infection: estimates of the in vivo mutation rate.PLoS pathogens · 2012Trial
- Assessment of direct-acting antiviral treatment outcomes in patients with chronic hepatitis C infected with various HCV genotypes: Insights from a real-world cohort in West Bengal, India.BMC infectious diseases · 2025Article
- Strategies and efforts in circumventing the emergence of antiviral resistance against conventional antivirals.npj antimicrobials and resistance · 2025Review
- Evolution shapes and conserves genomic signatures in viruses.Communications biology · 2024Article
- CRISPR/Cas9 as a New Antiviral Strategy for Treating Hepatitis Viral Infections.International journal of molecular sciences · 2023Review
- Accelerating antiviral drug discovery: lessons from COVID-19.Nature reviews. Drug discovery · 2023Review
- Sites of vulnerability in HCV E1E2 identified by comprehensive functional screening.Cell reports · 2022Article
- Mutational spectrum of hepatitis C virus in patients with chronic hepatitis C determined by single molecule real-time sequencing.Scientific reports · 2022Article
- A Review of Hepatitis B Virus and Hepatitis C Virus Immunopathogenesis.Journal of clinical and translational hepatology · 2021Review
- Hepatitis C Viral Replication Complex.Viruses · 2021Review
- Inhibition of viral RNA-dependent RNA polymerases with clinically relevant nucleotide analogs.The Enzymes · 2021Article
- Quantitative differences between intra-host HCV populations from persons with recently established and persistent infections.Virus evolution · 2021Article
- Rate-limiting pyrophosphate release by hepatitis C virus polymerase NS5B improves fidelity.The Journal of biological chemistry · 2020Article
- Article
- 2'-C-methylated nucleotides terminate virus RNA synthesis by preventing active site closure of the viral RNA-dependent RNA polymerase.The Journal of biological chemistry · 2019Article
- Mutational pathway maps and founder effects define the within-host spectrum of hepatitis C virus mutants resistant to drugs.PLoS pathogens · 2019Article
- Hepatitis C virus cell culture models: an encomium on basic research paving the road to therapy development.Medical microbiology and immunology · 2019Review
- Natural polymorphisms in the resistance associated sites of HCV-G1 NS5B domain and correlation with geographic origin of HCV isolates.Virology journal · 2018Article
- Modelling how responsiveness to interferon improves interferon-free treatment of hepatitis C virus infection.PLoS computational biology · 2018Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
The development of resistance to direct-acting antivirals (DAAs) targeting the hepatitis C virus (HCV) can compromise therapy. However, mechanisms that determine prevalence and frequency of resistance-conferring mutations remain elusive. Here, we studied the fidelity of the HCV RNA-dependent RNA polymerase NS5B in an attempt to link the efficiency of mismatch formation with genotypic changes observed in vivo. Enzyme kinetic measurements revealed unexpectedly high error rates (approximately 10(-3) per site) for G:U/U:G mismatches. The strong preference for G:U/U:G mismatches over all other mistakes correlates with a mutational bias in favor of transitions over transversions. Deep sequencing of HCV RNA samples isolated from 20 treatment-naïve patients revealed an approximately 75-fold difference in frequencies of the two classes of mutations. A stochastic model based on these results suggests that the bias toward transitions can also affect the selection of resistance-conferring mutations. Collectively, the data provide strong evidence to suggest that the nature of the nucleotide change can contribute to the genetic barrier in the development of resistance to DAAs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.