ArticlePLoS pathogens2011
Sequential bottlenecks drive viral evolution in early acute hepatitis C virus infection.
Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01707849 (An Unicenter, Prospective, Randomized, Pilot Study Comparing the Effect of Everolimus-containing Versus mTOR Inhibitor Free Immunosuppression in the Evolution of Hepatitis C Fibrosis After Liver Transplantation.), which is not on this map. Cited by 139 papers, 1 of them a synthesis that pooled it.
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.
An Unicenter, Prospective, Randomized, Pilot Study Comparing the Effect of Everolimus-containing Versus mTOR Inhibitor Free Immunosuppression in the Evolution of Hepatitis C Fibrosis After Liver Transplantation.
Who cites it
139 citing papers in PubMed, 1 synthesis or guideline pooled it, 265 citations in OpenAlex.
- Interpreting whole genome sequencing for investigating tuberculosis transmission: a systematic review.BMC medicine · 2016Pooled it
- High multiplicity infection following transplantation of hepatitis C virus-positive organs.The Journal of clinical investigation · 2019Trial
- Naturally occurring dominant drug resistance mutations occur infrequently in the setting of recently acquired hepatitis C.Antiviral therapy · 2015Trial
- 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
- Linkage-aware inference of fitness from short-read time-series genomic data.bioRxiv : the preprint server for biology · 2026Article
- Linkage-aware inference of fitness from short-read time-series genomic data.Virus evolution · 2026Article
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- Near extinction of the HBV quasispecies driven by the hard selective sweep in chronic hepatitis B.mBio · 2025Article
- Validation of signature molecular profiles of advanced HCV liver disease in hepatocellular carcinoma patients.Virus research · 2025Article
- Strategies and efforts in circumventing the emergence of antiviral resistance against conventional antivirals.npj antimicrobials and resistance · 2025Review
- Estimating the impact of direct acting antiviral therapy on the prevalence of hepatitis C virus infection using phylogenetics.Virus research · 2025Article
- A general and biomedical perspective of viral quasispecies.RNA (New York, N.Y.) · 2025Review
- ViralBottleneck: an R package for estimating viral transmission bottlenecks from deep sequencing data using multiple methods.Virus evolution · 2025Article
- Changes in intra-host mycovirus population diversity after vertical and horizontal transmission.Virus evolution · 2025Article
- Refining SARS-CoV-2 intra-host variation by leveraging large-scale sequencing data.NAR genomics and bioinformatics · 2024Article
- Multi-trait diversification in marine diatoms in constant and warmed environments.Proceedings. Biological sciences · 2024Article
- Vitamin D Fortification: A Promising Approach to Overcome Drug Resistance and Tolerance in Therapeutic Interventions.Scientifica · 2024Review
- Direct-acting antiviral resistance of Hepatitis C virus is promoted by epistasis.Nature communications · 2023Article
- Molecular Mechanisms of Resistance to Direct-Acting Antiviral (DAA) Drugs for the Treatment of Hepatitis C Virus Infections.Diagnostics (Basel, Switzerland) · 2023Article
79 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
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection.
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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.