A metabolic dependency of EBV can be targeted to hinder B cell transformation-Reference-Cited by-同舟云学术

A metabolic dependency of EBV can be targeted to hinder B cell transformation

Published:2024-07-05 Issue:6704 Volume:385 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Müller-Durovic Bojana¹^ORCID,Jäger Jessica¹^ORCID,Engelmann Christine²,Schuhmachers Patrick²^ORCID,Altermatt Sabine¹,Schlup Yannick¹,Duthaler Urs³^ORCID,Makowiec Celia¹^ORCID,Unterstab Gunhild¹^ORCID,Roffeis Sarah¹^ORCID,Xhafa Erta¹^ORCID,Assmann Nadine¹⁴^ORCID,Trulsson Fredrik¹^ORCID,Steiner Rebekah¹^ORCID,Edwards-Hicks Joy⁵^ORCID,West James⁵,Turner Lorinda⁵,Develioglu Leyla¹^ORCID,Ivanek Robert⁶^ORCID,Azzi Tarik⁷⁸^ORCID,Dehio Philippe¹^ORCID,Berger Christoph⁷^ORCID, ,Kuzmin Dmitry⁹¹⁰^ORCID,Saboz Sophie¹^ORCID,Mautner Josef¹¹^ORCID,Löliger Jordan¹,Geigges Marco¹^ORCID,Palianina Darya¹²^ORCID,Khanna Nina¹²^ORCID,Dirnhofer Stefan¹³^ORCID,Münz Christian²^ORCID,Bantug Glenn R.¹^ORCID,Hess Christoph¹⁵^ORCID,Berger Christoph,Hess Christoph,Koller Michael,Rossi Simona,Stampf Susanne,Müller Nicolas J.

Affiliation:

1. Immunobiology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.

2. Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.

3. Clinical Pharmacology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.

4. Axolabs GmbH, Kulmbach, Germany.

5. Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, UK.

6. Bioinformatics Facility, Department of Biomedicine, University Basel and University Hospital of Basel, Basel, Switzerland.

7. Experimental Infectious Diseases and Cancer Research, University Children’s Hospital of Zürich, Zürich, Switzerland.

8. Children’s Research Center, University Children’s Hospital of Zürich, Zürich, Switzerland.

9. Hornet Therapeutics Ltd, London, UK.

10. Department of Medical Oncology, Yale School of Medicine, New Haven, CT, USA.

11. Department of Gene Vectors, Helmholtz Centre Munich, Munich, Germany.

12. Laboratory of Infection Biology, Department of Biomedicine, University Basel and University Hospital of Basel, Basel, Switzerland.

13. Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.

Abstract

After 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 nicotinamide adenine dinucleotide (NAD) de novo biosynthesis by driving expression of the metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1) in infected B cells. Virus-enforced NAD production sustained mitochondrial complex I activity, to match adenosine triphosphate (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 therefore a druggable metabolic vulnerability of EBV-driven B cell transformation, opening therapeutic possibilities for EBV-related diseases.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/science.adk4898

Reference84 articles.

1. Epstein-Barr Virus Sequence Variation—Biology and Disease

2. Early Events Associated with Infection of Epstein-Barr Virus Infection of Primary B-Cells

3. Epstein-Barr virus nuclear protein 2 is a key determinant of lymphocyte transformation.

4. EBV Persistence in Memory B Cells In Vivo

5. The Immunology of Epstein-Barr Virus–Induced Disease

Cited by 5 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Epstein–Barr Viruses: Their Immune Evasion Strategies and Implications for Autoimmune Diseases;International Journal of Molecular Sciences;2024-07-26

2. Monovalent Pseudo-Natural Product Degraders Supercharge the Native Degradation of IDO1 by KLHDC3;2024-07-13

3. Proceedings of EIMN’s 1st European Immunometabolism Conference;Immunometabolism;2024-07

4. HUMAN HERPESVIRUS EPSTEIN-BARR (EBV) AND ITS PORCINE HOMOLOGS UNVEIL THE CONSERVED MECHANISM OF RECEPTOR ENDOCYTOSIS: NEW INSIGHTS INTO VIRAL IMMUNE EVASION AND ANTIVIRAL THERAPY POTENTIAL?;Slovenian Veterinary Research;2024-06-19

5. Targeting early EBV-driven IDO1-NAD metabolism as a potential therapeutic strategy for EBV-related diseases;The Innovation Medicine;2024