Epstein-Barr virus-driven metabolic alterations contribute to the viral lytic reactivation and tumor progression in nasopharyngeal carcinoma.
J Med Virol
; 96(5): e29634, 2024 May.
Article
en En
| MEDLINE
| ID: mdl-38682578
ABSTRACT
Metabolic reprogramming induced by Epstein-Barr virus (EBV) often mirrors metabolic changes observed in cancer cells. Accumulating evidence suggests that lytic reactivation is crucial in EBV-associated oncogenesis. The aim of this study was to explore the role of metabolite changes in EBV-associated malignancies and viral life cycle control. We first revealed that EBV (LMP1) accelerates the secretion of the oncometabolite D-2HG, and serum D-2HG level is a potential diagnostic biomarker for NPC. EBV (LMP1)-driven metabolite changes disrupts the homeostasis of global DNA methylation and demethylation, which have a significantly inhibitory effect on active DNA demethylation and 5hmC content. We found that loss of 5hmC indicates a poor prognosis for NPC patients, and that 5hmC modification is a restriction factor of EBV reactivation. We confirmed a novel EBV reactivation inhibitor, α-KG, which inhibits the expression of EBV lytic genes with CpG-containing ZREs and the latent-lytic switch by enhancing 5hmC modification. Our results demonstrate a novel mechanism of which metabolite abnormality driven by EBV controls the viral lytic reactivation through epigenetic modification. This study presents a potential strategy for blocking EBV reactivation, and provides potential targets for the diagnosis and therapy of NPC.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Activación Viral
/
Neoplasias Nasofaríngeas
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Herpesvirus Humano 4
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Metilación de ADN
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Infecciones por Virus de Epstein-Barr
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Carcinoma Nasofaríngeo
Límite:
Humans
Idioma:
En
Revista:
J Med Virol
Año:
2024
Tipo del documento:
Article
País de afiliación:
China