Paper Chase

Paper Chase is a research database designed to offer abstracts of research articles published in journals that have a highly rated impact factor as determined by ISI Impact Factor and PageRank. Abstracts are organized by date, with the most recently published papers listed first.

Cell metabolism
Sep 03, 2019 30 (3) 539-555.e11
Vol. 30, Issue 3, Medline Page 539-555.e11

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

Authors: Wang LW, 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
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.