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研究发现EB病毒促进B细胞转化
作者:小柯机器人 发布时间:2019/9/4 15:14:57

剑桥大学Michael P. Weekes和Benjamin E. Gewurz研究团队合作研究发现爱泼斯坦-巴尔二氏病毒(EBV)诱导的一碳代谢促进B细胞转化。 这一研究成果于2019年9月3日发表在国际学术期刊《细胞—代谢》上。

为了研究爱泼斯坦-巴尔二氏病毒(EBV)如何促进B细胞生长,研究人员通过基于串联-质谱标签的蛋白质组学对原发性B细胞在感染前和感染后的9个时间点进行分析,超过 8,000个宿主和29个病毒蛋白被定量,揭示线粒体重塑和诱导一碳(1C)代谢。 EBV编码的EBNA2及其靶蛋白MYC是上调中枢线粒体1C酶MTHFD2所必需的,MTHFD2在EBV驱动的B细胞生长和存活中起关键作用。 MTHFD2对于维持感染细胞中NADPH水平升高至关重要,并且线粒体NADPH的氧化减少B细胞增殖。后续研究强调了一碳代谢对核苷酸合成、NADPH产生和抗氧化的作用。 EBV促进丝氨酸的进入细胞和合成以增加1C代谢的通量。研究人员的研究结果突出了EBV诱导的1C代谢作为潜在的治疗靶点,并提供了病毒-癌代谢的新范例。

研究人员介绍,爱泼斯坦-巴尔二氏病毒(EBV)导致Burkitt、霍奇金和移植后B细胞淋巴瘤。但是, EBV如何重塑代谢途径来维持B细胞快速生长仍然很大程度上未知。

附:英文原文

Title: Epstein-Barr-Virus-Induced One-Carbon Metabolism Drives B Cell Transformation

Author: Vamsi K. Mootha, Michael P. Weekes,et al

Issue&Volume: Volume 30 Issue 3

Abstract: Epstein-Barr virus (EBV) causes Burkitt, Hodgkin, and post-transplant B cell lymphomas. How EBV remodels metabolic pathways to support rapid B cell outgrowth remains largely unknown. To gain insights, primary human B cells were profiled by tandem-mass-tag-based proteomics at rest and at nine time points after infection; >8,000 host and 29 viral proteins were quantified, revealing mitochondrial remodeling and induction of one-carbon (1C) metabolism. EBV-encoded EBNA2 and its target MYC were required for upregulation of the central mitochondrial 1C enzyme MTHFD2, which played key roles in EBV-driven B cell growth and survival. MTHFD2 was critical for maintaining elevated NADPH levels in infected cells, and oxidation of mitochondrial NADPH diminished B cell proliferation. Tracing studies underscored contributions of 1C to nucleotide synthesis, NADPH production, and redox defense. EBV upregulated import and synthesis of serine to augment 1C flux. Our results highlight EBV-induced 1C as a potential therapeutic target and provide a new paradigm for viral onco-metabolism.

DOI: https://doi.org/10.1016/j.cmet.2019.06.003

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30306-7

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx