Methionine metabolism controls the B cell EBV epigenome and viral latency.
dietary amino acid restriction
folate metabolism
gamma-herpesvirus
immunometabolism
lytic reactivation
methionine cycle
methionine metabolism
one-carbon metabolism
tumor virus
viral latency
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
06 09 2022
06 09 2022
Historique:
received:
20
02
2022
revised:
13
08
2022
accepted:
15
08
2022
entrez:
7
9
2022
pubmed:
8
9
2022
medline:
11
9
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36070681
pii: S1550-4131(22)00351-5
doi: 10.1016/j.cmet.2022.08.008
pmc: PMC9482757
mid: NIHMS1833895
pii:
doi:
Substances chimiques
Methionine
AE28F7PNPL
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1280-1297.e9Subventions
Organisme : NIDCR NIH HHS
ID : K99 DE031016
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI137337
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI164709
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA228700
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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