Evidence map›Paper›PMID 33497421›Full record

ArticlePLoS pathogens2021

A multi-omics approach to Epstein-Barr virus immortalization of B-cells reveals EBNA1 chromatin pioneering activities targeting nucleotide metabolism.

R Jason Lamontagne, Samantha S Soldan, Chenhe Su, Andreas Wiedmer, Kyoung Jae Won, Fang Lu, Aaron R Goldman, Jayamanna Wickramasinghe, Hsin-Yao Tang, David W Speicher and 3 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.3field-weighted citation impact, top 9% 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

33 citing papers in PubMed, 45 citations in OpenAlex.

  1. A guide to B cell metabolism.Nature reviews. Immunology · 2026
    Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. EBV INFECTION OUTCOMES DETERMINED BY MONOCYTE AND TbioRxiv : the preprint server for biology · 2025
    Article
  13. Article
  14. Article
  15. Review
  16. Chromatin Control of EBV Infection and Latency.Current topics in microbiology and immunology · 2025
    Article
  17. Review
  18. Article
  19. Multiple sclerosis and infection: history, EBV, and the search for mechanism.Microbiology and molecular biology reviews : MMBR · 2025
    Review
  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

13 authors at 2 institutions in 2 countries.

R Jason LamontagneThe Wistar Institute, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0002-9068-3348
Samantha S SoldanThe Wistar Institute, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0001-6263-519X
Chenhe SuThe Wistar Institute, Philadelphia, Pennsylvania, United States of America.
Andreas WiedmerThe Wistar Institute, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0002-1153-7896
Kyoung Jae WonBiotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
Fang LuThe Wistar Institute, Philadelphia, Pennsylvania, United States of America.
Aaron R GoldmanThe Wistar Institute, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0001-7605-9592
Jayamanna WickramasingheThe Wistar Institute, Philadelphia, Pennsylvania, United States of America.
Hsin-Yao TangThe Wistar Institute, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0003-1838-018X
David W SpeicherThe Wistar Institute, Philadelphia, Pennsylvania, United States of America.
Louise ShoweThe Wistar Institute, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0002-7818-4220
Andrew V KossenkovThe Wistar Institute, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0002-1536-0418
Paul M LiebermanThe Wistar Institute, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0002-3935-9921
The Wistar Institute · USUniversity of Copenhagen · DK

Funding

Tumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Luis J Montaner · 1985 to 2026
$75.9M
Regulation of Epstein-Barr Virus LatencyR01CA093606 · NCI · WISTAR INSTITUTE · PI LIEBERMAN, PAUL M. · 2002 to 2022
$6.7M
Epigenetic Regulation of Epstein-Barr Virus Latency ProgramsR01DE017336 · NIDCR · WISTAR INSTITUTE · PI PAUL M. LIEBERMAN · 2005 to 2026
$6.5M
Integration of Biomarker Signatures from Peripheral Blood for Diagnosis, Prognosis, Remission and Recurrence of Lung CancerU01CA200495 · NCI · WISTAR INSTITUTE · PI LIU, QIN, SHOWE, LOUISE C. · 2016 to 2021
$4.0M
Drugging EBNA1 to Treat EBV-Associated Cancers - Diversity SupplementR01CA259171 · NCI · WISTAR INSTITUTE · PI MESSICK, TROY E · 2021 to 2025
$3.3M
Regulation of EBV Latency by Purine Metabolism and SignalingR01AI153508 · NIAID · WISTAR INSTITUTE · PI TEMPERA, ITALO · 2021 to 2025
$2.3M
Advancing Cancer Research through Comprehensive Proteomics and Metabolomics AnalysesR50CA221838 · NCI · WISTAR INSTITUTE · PI Hsin-Yao Tang · 2017 to 2026
$2.1M
Integrative Approach to Comprehensive Analysis of High Throughput Data on a Cancer Center LevelR50CA211199 · NCI · WISTAR INSTITUTE · PI Andrew V Kossenkov · 2016 to 2026
$1.6M
NCI NIH HHS P30 CA010815NCI NIH HHS R01 CA093606NCI NIH HHS R01 CA259171NCI NIH HHS R50 CA211199NCI NIH HHS R50 CA221838NCI NIH HHS U01 CA200495NIAID NIH HHS R01 AI153508NIDCR NIH HHS R01 DE017336
6 · The paper itself

Abstract

Epstein-Barr virus (EBV) immortalizes resting B-lymphocytes through a highly orchestrated reprogramming of host chromatin structure, transcription and metabolism. Here, we use a multi-omics-based approach to investigate these underlying mechanisms. ATAC-seq analysis of cellular chromatin showed that EBV alters over a third of accessible chromatin during the infection time course, with many of these sites overlapping transcription factors such as PU.1, Interferon Regulatory Factors (IRFs), and CTCF. Integration of RNA-seq analysis identified a complex transcriptional response and associations with EBV nuclear antigens (EBNAs). Focusing on EBNA1 revealed enhancer-binding activity at gene targets involved in nucleotide metabolism, supported by metabolomic analysis which indicated that adenosine and purine metabolism are significantly altered by EBV immortalization. We further validated that adenosine deaminase (ADA) is a direct and critical target of the EBV-directed immortalization process. These findings reveal that purine metabolism and ADA may be useful therapeutic targets for EBV-driven lymphoid cancers.

Indexed as

Cell Transformation, ViralB-LymphocytesChromatinEpigenesis, GeneticEpstein-Barr Virus InfectionsEpstein-Barr Virus Nuclear AntigensHerpesvirus 4, HumanHost-Pathogen InteractionsHumansMetabolomeNucleotidesTranscriptomeViral ProteinsChromatinEBV-encoded nuclear antigen 1Epstein-Barr Virus Nuclear AntigensNucleotidesViral Proteins

Identifiers

PMID33497421
PMCPMC7864721
OpenAlexW3125790550

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.