Open AccessEpstein–Barr virus latency programs dynamically sensitize B cells to ferroptosis
Author(s) -
Eric Burton,
Jewel Voyer,
Benjamin E. Gewurz
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2118300119
Subject(s) - epstein–barr virus , virus , biology , reactive oxygen species , lymphoblast , cancer research , lymphoma , cell culture , programmed cell death , virology , microbiology and biotechnology , immunology , biochemistry , genetics , apoptosis
Significance Epstein–Barr virus (EBV) contributes to Burkitt lymphoma and post-transplant lymphoproliferative disease (PTLD). EBV-transforming programs activate lipid metabolism to convert B cells into immortalized lymphoblastoid cell lines (LCL), a PTLD model. We found that stages of EBV transformation generate lipid reactive oxygen species (ROS) byproducts to varying degrees, and that a Burkitt-like phase of B cell outgrowth requires lipid ROS detoxification by glutathione peroxidase 4 and its cofactor glutathione. Perturbation of this redox defense in early stages of transformation or in Burkitt cells triggered ferroptosis, a programmed cell death pathway. LCLs were less dependent on this defense, a distinction tied to EBV latency programs. This highlights ferroptosis induction as a potential therapeutic approach for prevention or treatment of certain EBV+ lymphomas.