EBV 的代谢依赖性可以阻碍 B 细胞转化。
A metabolic dependency of EBV can be targeted to hinder B cell transformation.
发表日期：2024 May 23
作者：
Bojana Müller-Durovic, Jessica Jäger, Christine Engelmann, Patrick Schuhmachers, Sabine Altermatt, Yannick Schlup, Urs Duthaler, Celia Makowiec, Gunhild Unterstab, Sarah Roffeis, Erta Xhafa, Nadine Assmann, Fredrik Trulsson, Rebekah Steiner, Joy Edwards-Hicks, James West, Lorinda Turner, Leyla Develioglu, Robert Ivanek, Tarik Azzi, Philippe Dehio, Christoph Berger, , Dmitry Kuzmin, Sophie Saboz, Josef Mautner, Jordan Löliger, Marco Geigges, Darya Palianina, Nina Khanna, Stefan Dirnhofer, Christian Münz, Glenn R Bantug, Christoph Hess, Christoph Berger, Christoph Hess, Michael Koller, Simona Rossi, Susanne Stampf, Nicolas J Müller
来源：
BIOMEDICINE & PHARMACOTHERAPY
摘要：
B 细胞感染后，EB 病毒 (EBV) 会参与介导细胞增殖和转化的宿主途径，导致病毒倾向于驱动免疫失调和淋巴瘤发生。我们发现EBV蛋白EBNA2通过驱动受感染B细胞中代谢酶IDO1的表达来启动NAD从头生物合成。病毒强制的 NAD 产生维持了线粒体复合物 I 的活性，以使 ATP 的产生与增殖和转化的生物能需求相匹配。在移植患者中，EBV 感染的 B 细胞中 IDO1 表达，以及 IDO1 活性增加的血清特征，先于淋巴瘤发生。在感染 EBV 的人源化小鼠中，抑制 IDO1 可减少病毒血症和淋巴瘤发生。因此，病毒协调的 NAD 生物合成是 EBV 驱动的 B 细胞转化的可药物代谢脆弱性，为 EBV 相关疾病提供了治疗可能性。
Following infection of B cells, Epstein Barr virus (EBV) engages host pathways that mediate cell proliferation and transformation, contributing to the propensity of the virus to drive immune dysregulation and lymphomagenesis. We found that the EBV protein EBNA2 initiates NAD de novo biosynthesis by driving expression of the metabolic enzyme IDO1 in infected B cells. Virus-enforced NAD production sustained mitochondrial complex I activity, to match ATP-production with bioenergetic requirements of proliferation and transformation. In transplant patients, IDO1 expression in EBV-infected B cells, and a serum signature of increased IDO1 activity, preceded development of lymphoma. In humanized mice infected with EBV, IDO1 inhibition reduced both viremia and lymphomagenesis. Virus-orchestrated NAD biosynthesis is, thus, a druggable metabolic vulnerability of EBV-driven B cell transformation-opening therapeutic possibilities for EBV-related diseases.