2. Academic Validation
  3. Epstein-Barr virus-driven metabolic alterations contribute to the viral lytic reactivation and tumor progression in nasopharyngeal carcinoma

Epstein-Barr virus-driven metabolic alterations contribute to the viral lytic reactivation and tumor progression in nasopharyngeal carcinoma

  • J Med Virol. 2024 May;96(5):e29634. doi: 10.1002/jmv.29634.
Feng Shi 1 2 3,  Li Shang 1 2 3,  Min Zhou 1 2 3,  Cong Lv 4,  Yueshuo Li 1 3,  Cheng Luo 1 2 3,  Na Liu 1 3,  Jingchen Lu 1 3,  Min Tang 1 3 5 6,  Xiangjian Luo 1 3 5 6,  Jing Xu 7,  Jia Fan 8,  Jian Zhou 8,  Qiang Gao 8,  Weizhong Wu 8,  Weihua Jia 9,  Hailin Wang 4,  Ya Cao 1 3 5 6 10 11
Affiliations

Affiliations

  • 1 Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, XiangYa Hospital, Central South University, Changsha, China.
  • 2 Department of Pathology, National Clinical Research Center for Geriatric Disorders/XiangYa Hospital, Central South University, Changsha, China.
  • 3 Key Laboratory of Carcinogenesis of National Health Commission, Cancer Research Institute and School of Basic Medical Science, Xiangya School of Medicine, Central South University, Changsha, China.
  • 4 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
  • 5 Department of Radiology, National Clinical Research Center for Geriatric Disorders/XiangYa Hospital, Central South University, Changsha, China.
  • 6 Molecular Imaging Research Center of Central South University, Changsha, China.
  • 7 Department of Otolaryngology Head and Neck Surgery, National Clinical Research Center for Geriatric Disorders/XiangYa Hospital, Central South University, Changsha, China.
  • 8 Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Zhongshan Hospital, Shanghai Medical School, Fudan University, Shanghai, China.
  • 9 State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.
  • 10 Research Center for Technologies of Nucleic Acid-Based Diagnostics and Therapeutics Hunan Province, Changsha, China.
  • 11 National Joint Engineering Research Center for Genetic Diagnostics of Infectious Diseases and Cancer, Changsha, China.
PMID: 38682578 DOI: 10.1002/jmv.29634
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.

Keywords

5‐hydroxymethylcytosine; DNA demethylation; D‐2‐hydroxyglutarate; Epstein‐Barr virus; viral lytic reactivation; α‐ketoglutarate.

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