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Cell Metab DOI:10.1016/j.cmet.2022.08.008

Methionine metabolism controls the B cell EBV epigenome and viral latency.

Publication TypeJournal Article
Year of Publication2022
AuthorsGuo, R, Liang, JHua, Zhang, Y, Lutchenkov, M, Li, Z, Wang, Y, Trujillo-Alonso, V, Puri, R, Giulino-Roth, L, Gewurz, BE
JournalCell Metab
Volume34
Issue9
Pages1280-1297.e9
Date Published2022 Sep 06
ISSN1932-7420
Abstract

Epstein-Barr virus (EBV) subverts host epigenetic pathways to switch between viral latency programs, colonize the B cell compartment, and reactivate. Within memory B cells, the reservoir for lifelong infection, EBV genomic DNA and histone methylation marks restrict gene expression. But this epigenetic strategy also enables EBV-infected tumors, including Burkitt lymphomas, to evade immune detection. Little is known about host cell metabolic pathways that support EBV epigenome landscapes. We therefore used amino acid restriction, metabolomic, and CRISPR approaches to identify that an abundant methionine supply and interconnecting methionine and folate cycles maintain Burkitt EBV gene silencing. Methionine restriction, or methionine cycle perturbation, hypomethylated EBV genomes and de-repressed latent membrane protein and lytic gene expression. Methionine metabolism also shaped EBV latency gene regulation required for B cell immortalization. Dietary methionine restriction altered murine Burkitt xenograft metabolomes and de-repressed EBV immunogens in vivo. These results highlight epigenetic/immunometabolism crosstalk supporting the EBV B cell life cycle and suggest therapeutic approaches.

DOI10.1016/j.cmet.2022.08.008
Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/36070681?dopt=Abstract

Alternate JournalCell Metab
PubMed ID36070681