ArticleGastroenterology2009
Selection pressure from neutralizing antibodies drives sequence evolution during acute infection with hepatitis C virus.
Article in Gastroenterology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.
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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
142 citing papers in PubMed, 232 citations in OpenAlex.
- Elucidation of hepatitis C virus transmission and early diversification by single genome sequencing.PLoS pathogens · 2012Trial
- Targets of protective immunity and opportunities in hepatitis C virus vaccine development.Nature reviews. Immunology · 2026Review
- mAbClust with AlphaFold 3 avoids hallucinations to define a quaternary broadly neutralizing HCV epitope.bioRxiv : the preprint server for biology · 2026Article
- Article
- Broadly Neutralizing Antibody Characteristics in Hepatitis C Virus Infection and Implications for Vaccine Design.Vaccines · 2025Review
- Sustained Long-Term Decline in Anti-HCV Neutralizing Antibodies in HIV/HCV-Coinfected Patients Five Years after HCV Therapy: A Retrospective Study.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Update on Hepatitis C Vaccine: Results and Challenges.Viruses · 2024Review
- Article
- Hepatitis C virus hypervariable region 1 antibodies interrupt E2-SR-B1 interaction to suppress viral infection.iScience · 2023Article
- HCV E1 influences the fitness landscape of E2 and may enhance escape from E2-specific antibodies.Virus evolution · 2023Article
- Convergent antibody responses are associated with broad neutralization of hepatitis C virus.Frontiers in immunology · 2023Article
- Repeated exposure to heterologous hepatitis C viruses associates with enhanced neutralizing antibody breadth and potency.The Journal of clinical investigation · 2022Article
- Mesenchymal stem cells-based therapy in liver diseases.Molecular biomedicine · 2022Review
- Computational identification of HCV neutralizing antibodies with a common HCDR3 disulfide bond motif in the antibody repertoires of infected individuals.Nature communications · 2022Review
- Intra-host analysis of hepaciviral glycoprotein evolution reveals signatures associated with viral persistence and clearance.Virus evolution · 2022Article
- In the era of rapid mRNA-based vaccines: Why is there no effective hepatitis C virus vaccine yet?World journal of hepatology · 2021Review
- Review
- Where to Next? Research Directions after the First Hepatitis C Vaccine Efficacy Trial.Viruses · 2021Review
- A conserved epitope III on hepatitis C virus E2 protein has alternate conformations facilitating cell binding or virus neutralization.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Characterization of linear epitope specificity of antibodies potentially contributing to spontaneous clearance of hepatitis C virus.PloS one · 2021Article
82 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
5 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsDespite recent characterization of hepatitis C virus-specific neutralizing antibodies, it is not clear to what extent immune pressure from neutralizing antibodies drives viral sequence evolution in vivo. This lack of understanding is particularly evident in acute infection, the phase when elimination or persistence of viral replication is determined and during which the importance of the humoral immune response has been largely discounted.
methodsWe analyzed envelope glycoprotein sequence evolution and neutralization of sequential autologous hepatitis C virus pseudoparticles in 8 individuals throughout acute infection.
resultsAmino acid substitutions occurred throughout the envelope genes, primarily within the hypervariable region 1 of E2. When individualized pseudoparticles expressing sequential envelope sequences were used to measure neutralization by autologous sera, antibodies neutralizing earlier sequence variants were detected at earlier time points than antibodies neutralizing later variants, indicating clearance and evolution of viral variants in response to pressure from neutralizing antibodies. To demonstrate the effects of amino acid substitution on neutralization, site-directed mutagenesis of a pseudoparticle envelope sequence revealed amino acid substitutions in hypervariable region 1 that were responsible for a dramatic decrease in neutralization sensitivity over time. In addition, high-titer neutralizing antibodies peaked at the time of viral clearance in all spontaneous resolvers, whereas chronically evolving subjects displayed low-titer or absent neutralizing antibodies throughout early acute infection.
conclusionsThese findings indicate that, during acute hepatitis C virus infection in vivo, virus-specific neutralizing antibodies drive sequence evolution and, in some individuals, play a role in determining the outcome 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.