Dataset Information

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

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 9 time points after infection. >8000 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Epstein-barr Virus Strain P3hr-1

TISSUE(S): B Cell, Blood

DISEASE(S): Lymphoma

SUBMITTER: Michael Weekes

LAB HEAD: Michael Weekes

PROVIDER: PXD013034 | Pride | 2019-06-28

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	EBVTransformationpeptides.xlsx	Xlsx
	EBVTransformationproteins.xlsx	Xlsx
	PRIDEsubmissionEBV_Transformation.docx	Other
	TRANSF_PM1_a04299.raw	Raw
	TRANSF_PM1_a04300.raw	Raw

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Publications

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

Wang Liang Wei LW Shen Hongying H Nobre Luis L Ersing Ina I Paulo Joao A JA Trudeau Stephen S Wang Zhonghao Z Smith Nicholas A NA Ma Yijie Y Reinstadler Bryn B Nomburg Jason J Sommermann Thomas T Cahir-McFarland Ellen E Gygi Steven P SP Mootha Vamsi K VK Weekes Michael P MP Gewurz Benjamin E BE

Cell metabolism 20190627 3

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 requi ...[more]

PMID: 31257153

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