ArticleMolecular biology and evolution2019
Fierce Selection and Interference in B-Cell Repertoire Response to Chronic HIV-1.
Article in Molecular biology and evolution, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 55 citations in OpenAlex.
- Dynamics of memory B cells and plasmablasts in healthy individuals.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A Sitewise Model of Natural Selection on Individual Antibodies via a Transformer-Encoder.Molecular biology and evolution · 2025Article
- Combining mutation and recombination statistics to infer clonal families in antibody repertoires.eLife · 2024Article
- A dynamical limit to evolutionary adaptation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- B cell phylogenetics in the single cell era.Trends in immunology · 2024Review
- Steering and controlling evolution - from bioengineering to fighting pathogens.Nature reviews. Genetics · 2023Review
- Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals.Nature communications · 2023Article
- Characterization of B-cell receptor clonality and immunoglobulin gene usage at multiple time points during active SARS-CoV-2 infection.Journal of medical virology · 2023Article
- A dynamical limit to evolutionary adaptation.bioRxiv : the preprint server for biology · 2023Article
- Inspecting the interaction between human immunodeficiency virus and the immune system through genetic turnover.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Genotype-phenotype landscapes for immune-pathogen coevolution.Trends in immunology · 2023Review
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- Design of an optimal combination therapy with broadly neutralizing antibodies to suppress HIV-1.eLife · 2022Article
- Affinity maturation for an optimal balance between long-term immune coverage and short-term resource constraints.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Longitudinal Dynamics of Human B-Cell Response at the Single-Cell Level in Response to Tdap Vaccination.Vaccines · 2021Article
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- Gut bacterial aggregates as living gels.eLife · 2021Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 3 countries.
Funding
Abstract
During chronic infection, HIV-1 engages in a rapid coevolutionary arms race with the host's adaptive immune system. While it is clear that HIV exerts strong selection on the adaptive immune system, the characteristics of the somatic evolution that shape the immune response are still unknown. Traditional population genetics methods fail to distinguish chronic immune response from healthy repertoire evolution. Here, we infer the evolutionary modes of B-cell repertoires and identify complex dynamics with a constant production of better B-cell receptor (BCR) mutants that compete, maintaining large clonal diversity and potentially slowing down adaptation. A substantial fraction of mutations that rise to high frequencies in pathogen-engaging CDRs of BCRs are beneficial, in contrast to many such changes in structurally relevant frameworks that are deleterious and circulate by hitchhiking. We identify a pattern where BCRs in patients who experience larger viral expansions undergo stronger selection with a rapid turnover of beneficial mutations due to clonal interference in their CDR3 regions. Using population genetics modeling, we show that the extinction of these beneficial mutations can be attributed to the rise of competing beneficial alleles and clonal interference. The picture is of a dynamic repertoire, where better clones may be outcompeted by new mutants before they fix.
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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.