Evidence map›Paper›PMID 25313069›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Efficient replication of Epstein-Barr virus in stratified epithelium in vitro.

Rachel M Temple, Junjia Zhu, Lynn Budgeon, Neil David Christensen, Craig Meyers, Clare E Sample

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 1 pooled it
7.6field-weighted citation impact, top 2% 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

95 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. EBV Genome Variations and Association With Diseases.Journal of medical virology · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Tissue and cellular tropism ofVeterinary pathology · 2024
    Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Rachel M TempleDepartments of Microbiology and Immunology.
Junjia ZhuPublic Health Sciences, and The Penn State Hershey Cancer Institute, Hershey, PA 17033.
Lynn BudgeonPathology, The Pennsylvania State University College of Medicine, Hershey, PA 17033; and.
Neil David ChristensenDepartments of Microbiology and Immunology, The Penn State Hershey Cancer Institute, Hershey, PA 17033 Pathology, The Pennsylvania State University College of Medicine, Hershey, PA 17033; and.
Craig MeyersDepartments of Microbiology and Immunology, The Penn State Hershey Cancer Institute, Hershey, PA 17033.
Clare E SampleDepartments of Microbiology and Immunology, The Penn State Hershey Cancer Institute, Hershey, PA 17033 csample@hmc.psu.edu.
Penn State Milton S. Hershey Medical Center · USPennsylvania State University · US

Funding

VIRUSES AND CANCERT32CA060395 · NCI · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI MEYERS, CRAIG M · 1994 to 2021
$4.3M
Organotypic Culture as a Model for EBV Infection of Epithelial CellsR21DE021583 · NIDCR · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI SAMPLE, CLARE E · 2010 to 2011
$425k
NCI NIH HHS T32 CA060395NCI NIH HHS T32 CA60395NIDCR NIH HHS DE021583NIDCR NIH HHS R21 DE021583
6 · The paper itself

Abstract

Epstein-Barr virus is a ubiquitous human herpesvirus associated with epithelial and lymphoid tumors. EBV is transmitted between human hosts in saliva and must cross the oral mucosal epithelium before infecting B lymphocytes, where it establishes a life-long infection. The latter process is well understood because it can be studied in vitro, but our knowledge of infection of epithelial cells has been limited by the inability to infect epithelial cells readily in vitro or to generate cell lines from EBV-infected epithelial tumors. Because epithelium exists as a stratified tissue in vivo, organotypic cultures may serve as a better model of EBV in epithelium than monolayer cultures. Here, we demonstrate that EBV is able to infect organotypic cultures of epithelial cells to establish a predominantly productive infection in the suprabasal layers of stratified epithelium, similar to that seen with Kaposi's-associated herpesvirus. These cells did express latency-associated proteins in addition to productive-cycle proteins, but a population of cells that exclusively expressed latency-associated viral proteins could not be detected; however, an inability to infect the basal layer would be unlike other herpesviruses examined in organotypic cultures. Furthermore, infection did not induce cellular proliferation, as it does in B cells, but instead resulted in cytopathic effects more commonly associated with productive viral replication. These data suggest that infection of epithelial cells is an integral part of viral spread, which typically does not result in the immortalization or enhanced growth of infected epithelial cells but rather in efficient production of virus.

Indexed as

Virus ReplicationAcyclovirAntiviral AgentsCell Culture TechniquesCell DifferentiationCytopathogenic Effect, ViralDNA, ViralEpstein-Barr Virus Nuclear AntigensGene Expression Regulation, ViralGingivaHerpesvirus 4, HumanHumansKeratinocytesKeratinsPalatine TonsilPlasmidsAcyclovirAntiviral AgentsBZLF1 protein, Herpesvirus 4, HumanDNA, ViralEBNA-2 protein, Human herpesvirus 4EBV-associated membrane antigen, Epstein-Barr virusEBV-encoded nuclear antigen 1Epstein-Barr virus encoded RNA 1Epstein-Barr Virus Nuclear AntigensinvolucrinKeratinsProtein PrecursorsRNA, ViralTrans-ActivatorsViral Matrix ProteinsViral ProteinsepithelialEpstein–Barr virusorganotypic cultureproductive replication

Identifiers

PMID25313069
PMCPMC4246336
OpenAlexW2029734559

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.