Evidence map›Paper›PMID 30787148›Full record

ArticleJournal of virology2019

Modeling Herpes Simplex Virus 1 Infections in Human Central Nervous System Neuronal Cells Using Two- and Three-Dimensional Cultures Derived from Induced Pluripotent Stem Cells.

Leonardo D'Aiuto, David C Bloom, Jennifer N Naciri, Adam Smith, Terri G Edwards, Lora McClain, Jason A Callio, Morgan Jessup, Joel Wood, Kodavali Chowdari and 8 more

Open access · hybridAbstract read
In one paragraph

Article in Journal of virology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 1 pooled it
10.7field-weighted citation impact, top 1% 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

80 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Organoids: physiologically relevantJournal of virology · 2025
    Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. A Comprehensive Review on Utilizing Human Brain Organoids to Study Neuroinflammation in Neurological Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025
    Review
  17. Review
  18. Host-membrane lipid composition controlsFrontiers in immunology · 2025
    Article
  19. Review
  20. Article

20 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

18 authors at 4 institutions in 2 countries.

Leonardo D'AiutoDepartment of Psychiatry, University of Pittsburgh School of Medicine Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania, USA daiutol@upmc.edu.ORCID 0000-0002-7102-2093
David C BloomDepartment of Molecular Genetics & Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA.
Jennifer N NaciriDepartment of Psychiatry, University of Pittsburgh School of Medicine Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania, USA.
Adam SmithDepartment of Psychiatry, University of Pittsburgh School of Medicine Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania, USA.
Terri G EdwardsDepartment of Molecular Genetics & Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA.
Lora McClainMagee-Women's Research Institute, Pittsburgh, Pennsylvania, USA.
Jason A CallioDepartment of Pathology, Division of Neuropathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Morgan JessupDepartment of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Joel WoodDepartment of Psychiatry, University of Pittsburgh School of Medicine Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania, USA.
Kodavali ChowdariDepartment of Psychiatry, University of Pittsburgh School of Medicine Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania, USA.
Matthew DemersDepartment of Psychiatry, University of Pittsburgh School of Medicine Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania, USA.
Eric E AbrahamsonDepartment of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Milos D IkonomovicDepartment of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Luigi ViggianoDepartment of Biology, University of Bari Aldo Moro, Bari, Italy.
Roberta De ZioDipartimento di Bioscienze, Biotecnologie e Biofarmaceutica, Università degli Studi di Bari, Bari, Italy.
Simon WatkinsDepartment of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Paul R KinchingtonDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.ORCID 0000-0002-1901-9970
Vishwajit L NimgaonkarDepartment of Psychiatry, University of Pittsburgh School of Medicine Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania, USA.
University of Pittsburgh · USUniversity of Bari Aldo Moro · ITUniversity of Florida · USMagee-Womens Research Institute · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOHN C. BYRD · 1988 to 2026
$158.0M
Virus Production and Manipulation of Protein/Gene Expression ModuleP30EY008098 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Ethan A Rossi · 1989 to 2026
$17.8M
A Neurobehavioral Family Study of SchizophreniaR01MH063480 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NIMGAONKAR, VISHWAJIT LAXMIKANT · 2001 to 2018
$6.1M
BASIC MICROBIOLOGY &INFECTIOUS DISEASEST32AI007110 · NIAID · UNIVERSITY OF FLORIDA · PI Stephanie M Karst · 1985 to 2026
$4.3M
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
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
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
Analysis of human-specific aspects of HSV-1 latency in human iPSC-derived neuronsR21NS096405 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI D'AIUTO, LEONARDO · 2016 to 2017
$428k
NCI NIH HHS P30 CA047904NEI NIH HHS P30 EY008098NIAID NIH HHS R01 AI122640NIAID NIH HHS T32 AI007110NIMH NIH HHS R01 MH063480NINDS NIH HHS R01 NS064022NINDS NIH HHS R21 NS096405NINDS NIH HHS R56 NS064022
6 · The paper itself

Abstract

Herpes simplex virus 1 (HSV-1) establishes latency in both peripheral nerve ganglia and the central nervous system (CNS). The outcomes of acute and latent infections in these different anatomic sites appear to be distinct. It is becoming clear that many of the existing culture models using animal primary neurons to investigate HSV-1 infection of the CNS are limited and not ideal, and most do not recapitulate features of CNS neurons. Human induced pluripotent stem cells (hiPSCs) and neurons derived from them are documented as tools to study aspects of neuropathogenesis, but few have focused on modeling infections of the CNS. Here, we characterize functional two-dimensional (2D) CNS-like neuron cultures and three-dimensional (3D) brain organoids made from hiPSCs to model HSV-1-human-CNS interactions. Our results show that (i) hiPSC-derived CNS neurons are permissive for HSV-1 infection; (ii) a quiescent state exhibiting key landmarks of HSV-1 latency described in animal models can be established in hiPSC-derived CNS neurons; (iii) the complex laminar structure of the organoids can be efficiently infected with HSV, with virus being transported from the periphery to the central layers of the organoid; and (iv) the organoids support reactivation of HSV-1, albeit less efficiently than 2D cultures. Collectively, our results indicate that hiPSC-derived neuronal platforms, especially 3D organoids, offer an extraordinary opportunity for modeling the interaction of HSV-1 with the complex cellular and architectural structure of the human CNS.

Indexed as

AnimalsCentral Nervous SystemChlorocebus aethiopsHerpes SimplexHerpesvirus 1, HumanHumansInduced Pluripotent Stem CellsNeuronsVero Cellsherpes simplex virus 1 (HSV-1)human induced pluripotent stem cells (hiPSCs)neurodegenerationorganoidthree-dimensional (3D) neuronal cultures

Identifiers

PMID30787148
PMCPMC6475775
OpenAlexW2916061513

What OpenQuestion holds

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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.