Trial reportPLoS pathogens2012
Quantifying the diversification of hepatitis C virus (HCV) during primary infection: estimates of the in vivo mutation rate.
Trial report in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
80 citing papers in PubMed, 152 citations in OpenAlex.
- High multiplicity infection following transplantation of hepatitis C virus-positive organs.The Journal of clinical investigation · 2019Trial
- Interferon-Free Treatment of Hepatitis C Virus in HIV/Hepatitis C Virus-Coinfected Subjects Results in Increased Serum Low-Density Lipoprotein Concentration.AIDS research and human retroviruses · 2016Trial
- Susceptibilities of genotype 1a, 1b, and 3 hepatitis C virus variants to the NS5A inhibitor elbasvir.Antimicrobial agents and chemotherapy · 2015Trial
- Elucidation of hepatitis C virus transmission and early diversification by single genome sequencing.PLoS pathogens · 2012Trial
- Virological and immunological determinants of hepatitis E virus infection outcomes.Current opinion in virology · 2025Review
- Impact of an oxidative RNA lesion on in vitro replication catalyzed by SARS-CoV-2 RNA-dependent RNA polymerase.The Journal of biological chemistry · 2025Article
- Article
- Contemporary Insights into Hepatitis C Virus: A Comprehensive Review.Microorganisms · 2024Review
- How robust are estimates of key parameters in standard viral dynamic models?PLoS computational biology · 2024Article
- Article
- The social role of defective viral genomes in chronic viral infections: a commentary on Leeks et al. 2023.Journal of evolutionary biology · 2023Article
- Mathematical modeling of plus-strand RNA virus replication to identify broad-spectrum antiviral treatment strategies.PLoS computational biology · 2023Article
- Viral proteases as therapeutic targets.Molecular aspects of medicine · 2022Review
- Mathematical modeling of plus-strand RNA virus replication to identify broad-spectrum antiviral treatment strategies.bioRxiv : the preprint server for biology · 2022Article
- Characteristics of hepatitis C virus resistance in an international cohort after a decade of direct-acting antivirals.JHEP reports : innovation in hepatology · 2022Article
- Assessing in vivo mutation frequencies and creating a high-resolution genome-wide map of fitness costs of Hepatitis C virus.PLoS genetics · 2022Article
- [Development approaches for vaccines against hepatitis C virus infections].Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz · 2022Review
- In the era of rapid mRNA-based vaccines: Why is there no effective hepatitis C virus vaccine yet?World journal of hepatology · 2021Review
- Novel and emerging mutations of SARS-CoV-2: Biomedical implications.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- A Review of Hepatitis B Virus and Hepatitis C Virus Immunopathogenesis.Journal of clinical and translational hepatology · 2021Review
20 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
12 authors at 2 institutions in 1 country.
Funding
Abstract
Hepatitis C virus (HCV) is present in the host with multiple variants generated by its error prone RNA-dependent RNA polymerase. Little is known about the initial viral diversification and the viral life cycle processes that influence diversity. We studied the diversification of HCV during acute infection in 17 plasma donors, with frequent sampling early in infection. To analyze these data, we developed a new stochastic model of the HCV life cycle. We found that the accumulation of mutations is surprisingly slow: at 30 days, the viral population on average is still 46% identical to its transmitted viral genome. Fitting the model to the sequence data, we estimate the median in vivo viral mutation rate is 2.5×10⁻⁵ mutations per nucleotide per genome replication (range 1.6-6.2×10⁻⁵), about 5-fold lower than previous estimates. To confirm these results we analyzed the frequency of stop codons (N = 10) among all possible non-sense mutation targets (M = 898,335), and found a mutation rate of 2.8-3.2×10⁻⁵, consistent with the estimate from the dynamical model. The slow accumulation of mutations is consistent with slow turnover of infected cells and replication complexes within infected cells. This slow turnover is also inferred from the viral load kinetics. Our estimated mutation rate, which is similar to that of other RNA viruses (e.g., HIV and influenza), is also compatible with the accumulation of substitutions seen in HCV at the population level. Our model identifies the relevant processes (long-lived cells and slow turnover of replication complexes) and parameters involved in determining the rate of HCV diversification.
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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.