Evidence map›Paper›PMID 24162921›Full record

ArticleMolecular biology and evolution2014

Deep sequencing of viral genomes provides insight into the evolution and pathogenesis of varicella zoster virus and its vaccine in humans.

Daniel P Depledge, Samit Kundu, Nancy J Jensen, Eleanor R Gray, Meleri Jones, Sharon Steinberg, Anne Gershon, Paul R Kinchington, D Scott Schmid, Francois Balloux and 2 more

Abstract read
In one paragraph

Article in Molecular biology and evolution, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
4.5field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

66 citing papers in PubMed, 104 citations in OpenAlex.

  1. Article
  2. Article
  3. Varicella zoster virus and the central nervous system.Nature reviews. Microbiology · 2026
    Review
  4. Review
  5. A fresh look at varicella vaccination.Human vaccines & immunotherapeutics · 2025
    Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Genomic and geographical structure of human cytomegalovirus.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  11. Article
  12. Varicella-Zoster Virus-Genetics, Molecular Evolution and Recombination.Current topics in microbiology and immunology · 2023
    Article
  13. Varicella Zoster Virus Neuronal Latency and Reactivation Modeled in Vitro.Current topics in microbiology and immunology · 2023
    Review
  14. Article
  15. Article
  16. Review
  17. Human herpesvirus diversity is altered in HLA class I binding peptides.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  18. Review
  19. Article
  20. Article

6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 2 countries.

Daniel P DepledgeMRC Centre for Medical Molecular Virology, Division of Infection and Immunity, London, United Kingdom.
Samit Kundu
Nancy J Jensen
Eleanor R Gray
Meleri Jones
Sharon Steinberg
Anne Gershon
Paul R Kinchington
D Scott Schmid
Francois Balloux
Richard A Nichols
Judith Breuer
Columbia University · USQueen Mary University of London · GBUniversity College London · GBUniversity of Pittsburgh · US

Funding

Virus Production and Manipulation of Protein/Gene Expression ModuleP30EY008098 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Ethan A Rossi · 1989 to 2026
$17.8M
Varicella zoster virus-Induced Pain in a Rat Model of Post-Herpetic NeuralgiaR01NS064022 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KINCHINGTON, PAUL R. · 2009 to 2019
$3.6M
Varicella zoster virus-Induced Pain in a Rat Model of Post-Herpetic NeuralgiaR56NS064022 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KINCHINGTON, PAUL R. · 2015 to 2015
$532k
Medical Research Council G0501446Medical Research Council G0700814Medical Research Council G0900950Medical Research Council G9721629NEI NIH HHS EY08098NEI NIH HHS P30 EY008098NINDS NIH HHS NS064022NINDS NIH HHS R01 NS064022NINDS NIH HHS R56 NS064022
6 · The paper itself

Abstract

Immunization with the vOka vaccine prevents varicella (chickenpox) in children and susceptible adults. The vOka vaccine strain comprises a mixture of genotypes and, despite attenuation, causes rashes in small numbers of recipients. Like wild-type virus, the vaccine establishes latency in neuronal tissue and can later reactivate to cause Herpes zoster (shingles). Using hybridization-based methodologies, we have purified and sequenced vOka directly from skin lesions. We show that alleles present in the vaccine can be recovered from the lesions and demonstrate the presence of a severe bottleneck between inoculation and lesion formation. Genotypes in any one lesion appear to be descended from one to three vaccine-genotypes with a low frequency of novel mutations. No single vOka haplotype and no novel mutations are consistently present in rashes, indicating that neither new mutations nor recombination with wild type are critical to the evolution of vOka rashes. Instead, alleles arising from attenuation (i.e., not derived from free-living virus) are present at lower frequencies in rash genotypes. We identify 11 loci at which the ancestral allele is selected for in vOka rash formation and show genotypes in rashes that have reactivated from latency cannot be distinguished from rashes occurring immediately after inoculation. We conclude that the vOka vaccine, although heterogeneous, has not evolved to form rashes through positive selection in the mode of a quasispecies, but rather alleles that were essentially neutral during the vaccine production have been selected against in the human subjects, allowing us to identify key loci for rash formation.

Indexed as

Genome, ViralAllelesEvolution, MolecularExanthemaGenotypeHerpesvirus 3, HumanHigh-Throughput Nucleotide SequencingHumansMolecular Sequence DataMutation RatePhylogenyPolymorphism, Single NucleotideSelection, GeneticSkinViral VaccinesViral Vaccinesalphaherpesviruspathogenesisviral evolution

Identifiers

PMID24162921
PMCPMC3907055
OpenAlexW2100772193

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.