Epstein-Barr virus latency programs dynamically sensitize B cells to ferroptosis.

Autor:	Burton EM; Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.; Harvard Program in Virology, Harvard Medical School, Boston, MA 02115.; Department of Microbiology, Harvard Medical School, Boston, MA 02115., Voyer J; Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115., Gewurz BE; Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.; Harvard Program in Virology, Harvard Medical School, Boston, MA 02115.; Department of Microbiology, Harvard Medical School, Boston, MA 02115.; Broad Institute of Harvard and MIT, Massachusetts Institute of Technology, Cambridge, MA 02142.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2022 Mar 15; Vol. 119 (11), pp. e2118300119. Date of Electronic Publication: 2022 Mar 11.
DOI:	10.1073/pnas.2118300119
Abstrakt:	SignificanceEpstein-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.
Databáze:	MEDLINE
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