Evidence map›Paper›PMID 26042814›Full record

ArticlePLoS pathogens2015

An in vitro model of latency and reactivation of varicella zoster virus in human stem cell-derived neurons.

Amos Markus, Ilana Lebenthal-Loinger, In Hong Yang, Paul R Kinchington, Ronald S Goldstein

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
6.1field-weighted citation impact, top 3% 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

55 citing papers in PubMed, 79 citations in OpenAlex.

  1. Review
  2. Varicella zoster virus and the central nervous system.Nature reviews. Microbiology · 2026
    Review
  3. Review
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  5. Biological relevance ofMicrobiology and molecular biology reviews : MMBR · 2025
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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

5 authors at 3 institutions in 3 countries.

Amos MarkusThe Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Ilana Lebenthal-LoingerThe Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
In Hong YangDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Singapore Institute for Neurotechnology (SINAPSE), National University of Singapore, Singapore.
Paul R KinchingtonDepartment of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Ronald S GoldsteinThe Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Bar-Ilan University · ILNational University of Singapore · SGUniversity 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
Molecular studies of VZV infection, latency and reactivation in human neurons in-vitroR01AI122640 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KINCHINGTON, PAUL R. · 2016 to 2020
$2.3M
A new in vitro neuron model of axonal transport and persistence of varicella zostR21NS082662 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KINCHINGTON, PAUL R. · 2013 to 2014
$390k
NEI NIH HHS EY08098NEI NIH HHS P30 EY008098NIAID NIH HHS R01 AI122640NINDS NIH HHS NS082662NINDS NIH HHS R21 NS082662
6 · The paper itself

Abstract

Varicella zoster virus (VZV) latency in sensory and autonomic neurons has remained enigmatic and difficult to study, and experimental reactivation has not yet been achieved. We have previously shown that human embryonic stem cell (hESC)-derived neurons are permissive to a productive and spreading VZV infection. We now demonstrate that hESC-derived neurons can also host a persistent non-productive infection lasting for weeks which can subsequently be reactivated by multiple experimental stimuli. Quiescent infections were established by exposing neurons to low titer cell-free VZV either by using acyclovir or by infection of axons in compartmented microfluidic chambers without acyclovir. VZV DNA and low levels of viral transcription were detectable by qPCR for up to seven weeks. Quiescently-infected human neuronal cultures were induced to undergo renewed viral gene and protein expression by growth factor removal or by inhibition of PI3-Kinase activity. Strikingly, incubation of cultures induced to reactivate at a lower temperature (34°C) resulted in enhanced VZV reactivation, resulting in spreading, productive infections. Comparison of VZV genome transcription in quiescently-infected to productively-infected neurons using RNASeq revealed preferential transcription from specific genome regions, especially the duplicated regions. These experiments establish a powerful new system for modeling the VZV latent state, and reveal a potential role for temperature in VZV reactivation and disease.

Indexed as

Embryonic Stem CellsHerpesvirus 3, HumanHerpes ZosterHumansIn Situ HybridizationIn Vitro TechniquesNeural Stem CellsNeuronsPolymerase Chain ReactionVirus ActivationVirus Latency

Identifiers

PMID26042814
PMCPMC4456082
OpenAlexW1591361110

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.