Evidence map›Paper›PMID 27078099›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

In vitro system using human neurons demonstrates that varicella-zoster vaccine virus is impaired for reactivation, but not latency.

Tomohiko Sadaoka, Daniel P Depledge, Labchan Rajbhandari, Arun Venkatesan, Judith Breuer, Jeffrey I Cohen

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 1 pooled it
5.0field-weighted citation impact, top 4% 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

56 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.

  1. Pooled it
  2. Varicella zoster virus and the central nervous system.Nature reviews. Microbiology · 2026
    Review
  3. Article
  4. Review
  5. Biological relevance ofMicrobiology and molecular biology reviews : MMBR · 2025
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Varicella Zoster Virus Neuronal Latency and Reactivation Modeled in Vitro.Current topics in microbiology and immunology · 2023
    Review
  12. Review
  13. Article
  14. Article
  15. Varicella-Zoster Virus-Genetics, Molecular Evolution and Recombination.Current topics in microbiology and immunology · 2023
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

6 authors at 5 institutions in 2 countries.

Tomohiko SadaokaMedical Virology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
Daniel P DepledgeDivision of Infection and Immunity, MRC Centre for Medical Molecular Virology, University College London, London WC1E 6BT, United Kingdom;
Labchan RajbhandariDivision of Neuroimmunology and Neuroinfectious Diseases, Department of Neurology, Johns Hopkins University School of Medicine, Johns Hopkins Hospital, Baltimore, MD 21287.
Arun VenkatesanDivision of Neuroimmunology and Neuroinfectious Diseases, Department of Neurology, Johns Hopkins University School of Medicine, Johns Hopkins Hospital, Baltimore, MD 21287.
Judith BreuerDivision of Infection and Immunity, MRC Centre for Medical Molecular Virology, University College London, London WC1E 6BT, United Kingdom;
Jeffrey I CohenMedical Virology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; jcohen@niaid.nih.gov.
Johns Hopkins Medicine · USMRC Laboratory for Molecular Cell Biology · GBNational Institute of Allergy and Infectious Diseases · USNational Institutes of Health · USUniversity College London · GB

Funding

Molecular Biology Of Varicella Zoster Virus InfectionZIAAI000430 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI COHEN, JEFFREY · 2009 to 2025
$4.5M
Medical Research Council G0700814MRF_ C0485
6 · The paper itself

Abstract

Varicella-zoster virus (VZV) establishes latency in human sensory and cranial nerve ganglia during primary infection (varicella), and the virus can reactivate and cause zoster after primary infection. The mechanism of how the virus establishes and maintains latency and how it reactivates is poorly understood, largely due to the lack of robust models. We found that axonal infection of neurons derived from hESCs in a microfluidic device with cell-free parental Oka (POka) VZV resulted in latent infection with inability to detect several viral mRNAs by reverse transcriptase-quantitative PCR, no production of infectious virus, and maintenance of the viral DNA genome in endless configuration, consistent with an episome configuration. With deep sequencing, however, multiple viral mRNAs were detected. Treatment of the latently infected neurons with Ab to NGF resulted in production of infectious virus in about 25% of the latently infected cultures. Axonal infection of neurons with vaccine Oka (VOka) VZV resulted in a latent infection similar to infection with POka; however, in contrast to POka, VOka-infected neurons were markedly impaired for reactivation after treatment with Ab to NGF. In addition, viral transcription was markedly reduced in neurons latently infected with VOka compared with POka. Our in vitro system recapitulates both VZV latency and reactivation in vivo and may be used to study viral vaccines for their ability to establish latency and reactivate.

Indexed as

Virus ActivationVirus LatencyCells, CulturedFluorescent Antibody TechniqueHerpesvirus 3, HumanHerpes ZosterHerpes Zoster VaccineHumansIn Vitro TechniquesMicrofluidicsNeural Stem CellsHerpes Zoster Vaccineherpesviruslatencyreactivationvaricella vaccinevaricella-zoster virus

Identifiers

PMID27078099
PMCPMC4855584
OpenAlexW2341565495

What OpenQuestion holds

Textmetadata
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.