Evidence map›Paper›PMID 31257153›Full record

ArticleCell metabolism2019

Epstein-Barr-Virus-Induced One-Carbon Metabolism Drives B Cell Transformation.

Liang Wei Wang, Hongying Shen, Luis Nobre, Ina Ersing, Joao A Paulo, Stephen Trudeau, Zhonghao Wang, Nicholas A Smith, Yijie Ma, Bryn Reinstadler and 7 more

Open access · hybridAbstract read
In one paragraph

Article in Cell metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.

0numbers the graph read from it
0cells of the map it votes in
125citing papers in PubMed
8.8field-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

125 citing papers in PubMed, 197 citations in OpenAlex.

  1. A guide to B cell metabolism.Nature reviews. Immunology · 2026
    Review
  2. Review
  3. 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
  4. A tonsil organoid model reveals Epstein-Barr virus-infected germinal center B cell states during primary infection.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Article
  6. Review
  7. Article
  8. MTHFD2: a promising metabolic checkpoint for diseases.Journal of translational medicine · 2026
    Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
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  15. Article
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  19. MTHFD2: A Retrospective and a Glance into the Future.International journal of molecular sciences · 2025
    Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 6 institutions in 3 countries.

Liang Wei WangGraduate Program in Virology, Division of Medical Sciences, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA; Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
Hongying ShenDepartment of Molecular Biology and Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Luis NobreCambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.
Ina ErsingDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA.
Joao A PauloDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Stephen TrudeauDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA.
Zhonghao WangDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA; Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China.
Nicholas A SmithDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA.
Yijie MaDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA.
Bryn ReinstadlerDepartment of Molecular Biology and Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Jason NomburgGraduate Program in Virology, Division of Medical Sciences, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA; Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA.
Thomas SommermannDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA.
Ellen Cahir-McFarlandDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA.
Steven P GygiDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Vamsi K MoothaDepartment of Molecular Biology and Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Michael P WeekesCambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK. Electronic address: mpw1001@cam.ac.uk.
Benjamin E GewurzGraduate Program in Virology, Division of Medical Sciences, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA; Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: bgewurz@bwh.harvard.edu.
Brigham and Women's Hospital · USHarvard University · USCenter for Systems Biology · USUniversity of Cambridge · GBBroad Institute · USWest China Hospital of Sichuan University · CN

Funding

New Sample Multiplexing Technologies to Identify Chemical Probes and Illuminate Ubiquitin BiologyR01GM067945 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI GYGI, STEVEN P · 2003 to 2024
$10.5M
Mitochondrial Parts, Pathways, and PathogenesisR35GM122455 · NIGMS · BROAD INSTITUTE, INC. · PI MOOTHA, VAMSI KRISHNA · 2017 to 2021
$4.0M
Metabolic Network Remodeling in Epstein-Barr Virus LymphomagenesisR01AI137337 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI GEWURZ, BENJAMIN ELISON · 2018 to 2022
$2.2M
Advancing Multiplexed Isobaric Tag-based Strategies for Proteome ProfilingR01GM132129 · NIGMS · HARVARD MEDICAL SCHOOL · PI PAULO, JOAO A · 2019 to 2023
$1.7M
An integrated approach to the study of mitochondrial vitamin B12 pathway and type II fatty acid synthesisR00GM124296 · NIGMS · YALE UNIVERSITY · PI SHEN, HONGYING · 2020 to 2022
$747k
Resolving the role of nicotine-mediated phosphorylation on pancreatic fibrosisK01DK098285 · NIDDK · HARVARD MEDICAL SCHOOL · PI PAULO, JOAO A · 2013 to 2017
$638k
An integrated approach to the study of mitochondrial vitamin B12 pathway and type II fatty acid synthesisK99GM124296 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI SHEN, HONGYING · 2017 to 2018
$180k
Howard Hughes Medical InstituteNIAID NIH HHS R01 AI137337NIDDK NIH HHS K01 DK098285NIGMS NIH HHS K99 GM124296NIGMS NIH HHS R00 GM124296NIGMS NIH HHS R01 GM067945NIGMS NIH HHS R01 GM132129NIGMS NIH HHS R35 GM122455Wellcome TrustWellcome Trust 108070/Z/15/Z
6 · The paper itself

Abstract

Epstein-Barr virus (EBV) causes Burkitt, Hodgkin, and post-transplant B cell lymphomas. How EBV remodels metabolic pathways to support rapid B cell outgrowth remains largely unknown. To gain insights, primary human B cells were profiled by tandem-mass-tag-based proteomics at rest and at nine time points after infection; >8,000 host and 29 viral proteins were quantified, revealing mitochondrial remodeling and induction of one-carbon (1C) metabolism. EBV-encoded EBNA2 and its target MYC were required for upregulation of the central mitochondrial 1C enzyme MTHFD2, which played key roles in EBV-driven B cell growth and survival. MTHFD2 was critical for maintaining elevated NADPH levels in infected cells, and oxidation of mitochondrial NADPH diminished B cell proliferation. Tracing studies underscored contributions of 1C to nucleotide synthesis, NADPH production, and redox defense. EBV upregulated import and synthesis of serine to augment 1C flux. Our results highlight EBV-induced 1C as a potential therapeutic target and provide a new paradigm for viral onco-metabolism.

Indexed as

Cell Transformation, ViralAminohydrolasesB-LymphocytesEpstein-Barr Virus InfectionsEpstein-Barr Virus Nuclear AntigensFemaleFolic AcidGlycolysisHEK293 CellsHerpesvirus 4, HumanHumansLymphocyte ActivationMethylenetetrahydrofolate Dehydrogenase (NADP)MitochondriaMultifunctional EnzymesNADPAminohydrolasesEpstein-Barr Virus Nuclear AntigensFolic AcidMethylenetetrahydrofolate Dehydrogenase (NADP)MTHFD2 protein, humanMultifunctional EnzymesMYC protein, humanNADPProteomeProto-Oncogene Proteins c-mycSerineB-cell activationde novo serine synthesisfolateisotope tracingmetabolic remodelingmitochondrial one-carbon metabolismquantitative proteomicstandem mass tagtumor virusvirus oncoprotein

Identifiers

PMID31257153
PMCPMC6720460
OpenAlexW2954390295

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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.