Faculty Opinions recommendation of Epstein-Barr-Virus-Induced One-Carbon Metabolism Drives B Cell Transformation.
Year: 2019
Type: peer-review
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 tandemmass-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 EBVdriven 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 poten-tial therapeutic target and provide a new paradigm for viral onco-metabolism.
Author: Micah Luftig
Institution: Duke Medical Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4247832655