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

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  • معلومة اضافية
    • Corporate Authors:
      Swiss Transplant Cohort Study
    • المصدر:
      Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE
    • بيانات النشر:
      Publication: : Washington, DC : American Association for the Advancement of Science
      Original Publication: New York, N.Y. : [s.n.] 1880-
    • الموضوع:
      Adenosine Triphosphate*/metabolism ; B-Lymphocytes*/immunology ; B-Lymphocytes*/metabolism ; Cell Transformation, Viral* ; Epstein-Barr Virus Infections*/virology ; Epstein-Barr Virus Nuclear Antigens*/metabolism ; Herpesvirus 4, Human*/physiology ; Indoleamine-Pyrrole 2,3,-Dioxygenase*/metabolism ; Indoleamine-Pyrrole 2,3,-Dioxygenase*/genetics ; NAD*/metabolism; Animals ; Humans ; Mice ; Cell Proliferation ; Electron Transport Complex I/metabolism ; Lymphoma/virology ; Viral Proteins ; Viremia
    • نبذة مختصرة :
      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.
    • Contributed Indexing:
      Investigator: C Berger; C Hess; M Koller; S Rossi; S Stampf; NJ Müller
    • الرقم المعرف:
      8L70Q75FXE (Adenosine Triphosphate)
      0 (EBNA-2 protein, Human herpesvirus 4)
      EC 7.1.1.2 (Electron Transport Complex I)
      0 (Epstein-Barr Virus Nuclear Antigens)
      0 (IDO1 protein, human)
      0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
      0U46U6E8UK (NAD)
      0 (Viral Proteins)
    • الموضوع:
      Date Created: 20240523 Date Completed: 20240704 Latest Revision: 20240802
    • الموضوع:
      20240803
    • الرقم المعرف:
      10.1126/science.adk4898
    • الرقم المعرف:
      38781354