Evidence map›Paper›PMID 28604764›Full record

ArticleOncogenesis2017

Limited nucleotide pools restrict Epstein-Barr virus-mediated B-cell immortalization.

A Y Hafez, J E Messinger, K McFadden, G Fenyofalvi, C N Shepard, G M Lenzi, B Kim, M A Luftig

Open access · goldAbstract read
In one paragraph

Article in Oncogenesis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

27 citing papers in PubMed, 36 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Chromatin Control of EBV Infection and Latency.Current topics in microbiology and immunology · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Contribution of viral and bacterial infections to senescence and immunosenescence.Frontiers in cellular and infection microbiology · 2023
    Review
  12. Review
  13. Review
  14. Review
  15. Oncogenic Viruses as Entropic Drivers of Cancer Evolution.Frontiers in virology (Lausanne, Switzerland) · 2021
    Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review
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

8 authors at 2 institutions in 1 country.

A Y HafezDepartment of Molecular Genetics and Microbiology, Center for Virology, Duke University School of Medicine, Durham, NC, USA.
J E MessingerDepartment of Molecular Genetics and Microbiology, Center for Virology, Duke University School of Medicine, Durham, NC, USA.
K McFaddenDepartment of Molecular Genetics and Microbiology, Center for Virology, Duke University School of Medicine, Durham, NC, USA.
G FenyofalviDepartment of Molecular Genetics and Microbiology, Center for Virology, Duke University School of Medicine, Durham, NC, USA.
C N ShepardDepartment of Pediatrics, Center for Drug Discovery, School of Medicine, Emory University, Atlanta, GA, USA.
G M LenziDepartment of Pediatrics, Center for Drug Discovery, School of Medicine, Emory University, Atlanta, GA, USA.
B KimDepartment of Pediatrics, Center for Drug Discovery, School of Medicine, Emory University, Atlanta, GA, USA.
M A LuftigDepartment of Molecular Genetics and Microbiology, Center for Virology, Duke University School of Medicine, Durham, NC, USA.
Duke University · USEmory 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
Graduate Training in the Pharmacological StudiesT32GM008602 · NIGMS · EMORY UNIVERSITY · PI HALL, RANDY A. · 1996 to 2021
$5.1M
Replication fidelity and lentiviral pathogenesisR01AI049781 · NIAID · UNIVERSITY OF ROCHESTER · PI KIM, BAEK · 2002 to 2016
$4.9M
SAMHD1 controls dNTP pool and HIV sensitivity to NRTIsR01GM104198 · NIGMS · UNIVERSITY OF ROCHESTER · PI KIM, BAEK · 2012 to 2018
$2.3M
Replicational Fidelity and Lentivial PathogenesisR56AI049781 · NIAID · EMORY UNIVERSITY · PI KIM, BAEK · 2017 to 2017
$390k
NCI NIH HHS R01 CA140337NCI NIH HHS T32 CA009111NIAID NIH HHS P30 AI064518NIAID NIH HHS R01 AI049781NIAID NIH HHS R56 AI049781NIAID NIH HHS T32 AI007392NIGMS NIH HHS R01 GM104198NIGMS NIH HHS T32 GM008602
6 · The paper itself

Abstract

Activation of cellular oncogenes as well as infection with tumor viruses can promote aberrant proliferation and activation of the host DNA damage response. Epstein-Barr virus (EBV) infection of primary human B cells induces a transient period of hyper-proliferation, but many of these infected cells succumb to an ataxia telangiectasia mutated/checkpoint kinase 2 (ATM/Chk2)-mediated senescence-like growth arrest. In this study, we assessed the role of DNA replicative stress and nucleotide pool levels in limiting EBV-infected B-cell outgrowth. We found that EBV triggered activation of the ataxia telangiectasia and Rad3-related (ATR) signaling pathway in the early rapidly proliferating cells, which were also significantly more sensitive to inhibition of the ATR pathway than late attenuated proliferating cells. Through nuclear halo assays, we determined that early EBV-infected cells displayed increased replicative stress and DNA damage relative to late proliferating cells. Finally, we found that early after infection, hyper-proliferating B cells exhibited limited deoxyribonucleotide triphosphate (dNTP) pools compared with late proliferating and EBV-immortalized lymphoblastoid cell lines with a specific loss of purine dNTPs. Importantly, supplementation with exogenous nucleosides before the period of hyper-proliferation markedly enhanced B-cell immortalization by EBV and rescued replicative stress. Together our results suggest that purine dNTP biosynthesis has a critical role in the early stages of EBV-mediated B-cell immortalization.

Identifiers

PMID28604764
PMCPMC5519195
OpenAlexW2624297192

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Registered trials

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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.