Evidence map›Paper›PMID 26802124›Full record

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

Metabolic stress is a barrier to Epstein-Barr virus-mediated B-cell immortalization.

Karyn McFadden, Amy Y Hafez, Rigel Kishton, Joshua E Messinger, Pavel A Nikitin, Jeffrey C Rathmell, Micah A Luftig

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 82 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 1 pooled it
8.1field-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

82 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.

  1. Guideline
  2. A guide to B cell metabolism.Nature reviews. Immunology · 2026
    Review
  3. Review
  4. SIRT2 deacylase modulators control B cell metabolic reprogramming in EBV infection and mitogenic activation.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Sp140L functions as a herpesvirus restriction factor suppressing viral transcription and activating interferon-stimulated genes.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Multiple sclerosis and infection: history, EBV, and the search for mechanism.Microbiology and molecular biology reviews : MMBR · 2025
    Review
  16. Article
  17. Article
  18. Glucose-independent human cytomegalovirus replication is supported by metabolites that feed upper glycolytic branches.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  19. Review
  20. Article

22 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

7 authors at 1 institution in 1 country.

Karyn McFaddenDepartment of Molecular Genetics and Microbiology, Center for Virology, Duke University School of Medicine, Durham, NC 27710;
Amy Y HafezDepartment of Molecular Genetics and Microbiology, Center for Virology, Duke University School of Medicine, Durham, NC 27710;
Rigel KishtonDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710;
Joshua E MessingerDepartment of Molecular Genetics and Microbiology, Center for Virology, Duke University School of Medicine, Durham, NC 27710;
Pavel A NikitinDepartment of Molecular Genetics and Microbiology, Center for Virology, Duke University School of Medicine, Durham, NC 27710;
Jeffrey C RathmellDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710; Department of Immunology, Duke University School of Medicine, Durham, NC 27710; Duke Molecular Physiology Institute, Duke University, Durham, NC 27710.
Micah A LuftigDepartment of Molecular Genetics and Microbiology, Center for Virology, Duke University School of Medicine, Durham, NC 27710; micah.luftig@duke.edu.
Duke University · US

Funding

Social and Behavioral Sciences CoreP30AI064518 · NIAID · DUKE UNIVERSITY · PI Nwora Lance Okeke · 2005 to 2026
$50.5M
Ruth L. Kirschstein National Research Service Award (NRSA)- T32T32AI007392 · NIAID · DUKE UNIVERSITY · PI Amy Lynn Corneli, Guido Ferrari · 1990 to 2026
$9.8M
Viral Oncology Training GrantT32CA009111 · NCI · DUKE UNIVERSITY · PI LUFTIG, MICAH A. · 1985 to 2023
$8.9M
Host pathways regulating Epstein-Barr virus-mediated B cell growth transformationR01CA140337 · NCI · DUKE UNIVERSITY · PI LUFTIG, MICAH ALAN · 2011 to 2025
$5.9M
Exploiting metabolic vulnerabilities of CD4 T cell subsets to control inflammatory diseaseR01DK105550 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jeffrey C Rathmell · 2015 to 2026
$4.7M
NCI NIH HHS R01 CA140337NCI NIH HHS R01-CA140337NCI NIH HHS T32 CA009111NCI NIH HHS T32-CA009111NIAID NIH HHS 5P30 AI064518NIAID NIH HHS P30 AI064518NIAID NIH HHS T32 AI007392NIAID NIH HHS T32-AI007392NIDDK NIH HHS R01 DK105550NIDDK NIH HHS R01-DK105550
6 · The paper itself

Abstract

Epstein-Barr virus (EBV) is an oncogenic herpesvirus that has been causally linked to the development of B-cell and epithelial malignancies. Early after infection, EBV induces a transient period of hyperproliferation that is suppressed by the activation of the DNA damage response and a G1/S-phase growth arrest. This growth arrest prevents long-term outgrowth of the majority of infected cells. We developed a method to isolate and characterize infected cells that arrest after this early burst of proliferation and integrated gene expression and metabolic profiling to gain a better understanding of the pathways that attenuate immortalization. We found that the arrested cells have a reduced level of mitochondrial respiration and a decrease in the expression of genes involved in the TCA cycle and oxidative phosphorylation. Indeed, the growth arrest in early infected cells could be rescued by supplementing the TCA cycle. Arrested cells were characterized by an increase in the expression of p53 pathway gene targets, including sestrins leading to activation of AMPK, a reduction in mTOR signaling, and, consequently, elevated autophagy that was important for cell survival. Autophagy was also critical to maintain early hyperproliferation during metabolic stress. Finally, in assessing the metabolic changes from early infection to long-term outgrowth, we found concomitant increases in glucose import and surface glucose transporter 1 (GLUT1) levels, leading to elevated glycolysis, oxidative phosphorylation, and suppression of basal autophagy. Our study demonstrates that oncogene-induced senescence triggered by a combination of metabolic and genotoxic stress acts as an intrinsic barrier to EBV-mediated transformation.

Indexed as

Cell Transformation, ViralStress, PhysiologicalAutophagyB-LymphocytesCell Cycle CheckpointsCell ProliferationCell RespirationCellular SenescenceDeoxyglucoseDimethylformamideDNA DamageDNA ReplicationHerpesvirus 4, HumanHumansMechanistic Target of Rapamycin Complex 1MetabolomicsDeoxyglucoseDimethylformamideMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesTOR Serine-Threonine KinasesTranscription FactorsTumor Suppressor Protein p53autophagyB cellEpstein–Barr virusmetabolismoncogene-induced senescence

Identifiers

PMID26802124
PMCPMC4760815
OpenAlexW2259398295

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.