Epstein-Barr virus latency programs dynamically sensitize B cells to ferroptosis.
Proc Natl Acad Sci U S A
; 119(11): e2118300119, 2022 03 15.
Article
in En
| MEDLINE
| ID: mdl-35275790
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
B-Lymphocytes
/
Cell Transformation, Viral
/
Burkitt Lymphoma
/
Virus Latency
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Herpesvirus 4, Human
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Ferroptosis
Limits:
Humans
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2022
Document type:
Article