美国布莱根妇女医院Benjamin E. Gewurz小组的最新研究发现，甲硫氨酸代谢调控EB病毒(EBV)感染者B细胞的表观基因组和病毒潜伏期。2022年9月6日出版的《细胞-代谢》发表了这项成果。

研究人员使用氨基酸限制、代谢组学和CRISPR方法来确定充足的甲硫氨酸供应、甲硫氨酸和叶酸循环交叉以及维持Burkitt EBV基因沉默对EBV表观基因组的影响。甲硫氨酸限制或甲硫氨酸循环扰动、低甲基化EBV基因组和潜膜蛋白去抑制和裂解基因表达。甲硫氨酸代谢也调控了B细胞永生化所需的EBV潜伏基因。限制饮食甲硫氨酸改变了小鼠Burkitt异种移物的代谢组，并在体内抑制了EBV免疫原。这些结果表明EBV与B细胞生命周期的表观遗传/免疫代谢存在关联，并提出了治疗方法。

据介绍，EBV会导致宿主的表观遗传途径在病毒潜伏基序、定殖B细胞区室和重新激活之间切换。在记忆B细胞中，终身感染的储存库、EBV基因组DNA和组蛋白甲基化标记限制了基因表达。但这种表观遗传策略也使EBV感染的肿瘤（包括伯基特淋巴瘤）细胞能够逃避免疫监视。然而关于宿主细胞代谢如何促进EBV表观基因组改变的途径知之甚少。

附：英文原文

Title: Methionine metabolism controls the B cell EBV epigenome and viral latency

Author: Rui Guo, Jin Hua Liang, Yuchen Zhang, Michael Lutchenkov, Zhixuan Li, Yin Wang, Vicenta Trujillo-Alonso, Rishi Puri, Lisa Giulino-Roth, Benjamin E. Gewurz

Issue&Volume: 2022/09/06

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

DOI: 10.1016/j.cmet.2022.08.008

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00351-5