高级检索
当前位置: 首页 > 详情页

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

文献详情

资源类型:
Pubmed体系:

收录情况: ◇ 自然指数

机构: [1]Graduate Program in Virology, Division of Medical Sciences, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA [2]Division of Infectious Diseases, Department of Medicine, Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, MA 02115, USA [3]Department of Molecular Biology and Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA [4]Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA [5]Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA [6]Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK [7]Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA [8]Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China [9]Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA
出处:
ISSN:

摘要:
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. Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

基金:
语种:
PubmedID:
中科院(CAS)分区:
出版当年[2019]版:
大类 | 1 区 生物学
小类 | 1 区 细胞生物学 1 区 内分泌学与代谢
最新[2023]版:
大类 | 1 区 生物学
小类 | 1 区 细胞生物学 1 区 内分泌学与代谢
第一作者:
第一作者机构: [1]Graduate Program in Virology, Division of Medical Sciences, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA [2]Division of Infectious Diseases, Department of Medicine, Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, MA 02115, USA [9]Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA
共同第一作者:
通讯作者:
通讯机构: [1]Graduate Program in Virology, Division of Medical Sciences, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA [2]Division of Infectious Diseases, Department of Medicine, Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, MA 02115, USA [5]Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA [9]Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA
推荐引用方式(GB/T 7714):
APA:
MLA:

资源点击量:46425 今日访问量:0 总访问量:3323 更新日期:2024-11-01 建议使用谷歌、火狐浏览器 常见问题

版权所有©2020 四川省肿瘤医院 技术支持:重庆聚合科技有限公司 地址:成都市人民南路四段55号