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Cell Metab DOI:10.1016/j.cmet.2019.06.003

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

Publication TypeJournal Article
Year of Publication2019
AuthorsWang, LWei, Shen, H, Nobre, L, Ersing, I, Paulo, JA, Trudeau, S, Wang, Z, Smith, NA, Ma, Y, Reinstadler, B, Nomburg, J, Sommermann, T, Cahir-McFarland, E, Gygi, SP, Mootha, VK, Weekes, MP, Gewurz, BE
JournalCell Metab
Volume30
Issue3
Pages539-555.e11
Date Published2019 Sep 03
ISSN1932-7420
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.

DOI10.1016/j.cmet.2019.06.003
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/31257153?dopt=Abstract

Alternate JournalCell Metab.
PubMed ID31257153
PubMed Central IDPMC6720460
Grant ListR01 GM067945 / GM / NIGMS NIH HHS / United States
R01 AI123420 / AI / NIAID NIH HHS / United States
R01 AI137337 / AI / NIAID NIH HHS / United States
K99 GM124296 / GM / NIGMS NIH HHS / United States
R35 GM122455 / GM / NIGMS NIH HHS / United States