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A metabolic dependency of EBV can be targeted to hinder B cell transformation.
Müller-Durovic, Bojana; Jäger, Jessica; Engelmann, Christine; Schuhmachers, Patrick; Altermatt, Sabine; Schlup, Yannick; Duthaler, Urs; Makowiec, Celia; Unterstab, Gunhild; Roffeis, Sarah; Xhafa, Erta; Assmann, Nadine; Trulsson, Fredrik; Steiner, Rebekah; Edwards-Hicks, Joy; West, James; Turner, Lorinda; Develioglu, Leyla; Ivanek, Robert; Azzi, Tarik; Dehio, Philippe; Berger, Christoph; Kuzmin, Dmitry; Saboz, Sophie; Mautner, Josef; Löliger, Jordan; Geigges, Marco; Palianina, Darya; Khanna, Nina; Dirnhofer, Stefan; Münz, Christian; Bantug, Glenn R; Hess, Christoph.
Afiliação
  • Müller-Durovic B; Immunobiology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
  • Jäger J; Immunobiology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
  • Engelmann C; Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
  • Schuhmachers P; Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
  • Altermatt S; Immunobiology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
  • Schlup Y; Immunobiology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
  • Duthaler U; Clinical Pharmacology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
  • Makowiec C; Immunobiology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
  • Unterstab G; Immunobiology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
  • Roffeis S; Immunobiology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
  • Xhafa E; Immunobiology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
  • Assmann N; Immunobiology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
  • Trulsson F; Axolabs GmbH, Kulmbach, Germany.
  • Steiner R; Immunobiology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
  • Edwards-Hicks J; Immunobiology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
  • West J; Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, UK.
  • Turner L; Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, UK.
  • Develioglu L; Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, UK.
  • Ivanek R; Immunobiology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
  • Azzi T; Bioinformatics Facility, Department of Biomedicine, University Basel and University Hospital of Basel, Basel, Switzerland.
  • Dehio P; Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zürich, Zürich, Switzerland.
  • Berger C; Children's Research Center, University Children's Hospital of Zürich, Zürich, Switzerland.
  • Kuzmin D; Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zürich, Zürich, Switzerland.
  • Mautner J; Hornet Therapeutics Ltd, London, UK.
  • Löliger J; Department of Medical Oncology, Yale School of Medicine, New Haven, CT, USA.
  • Geigges M; Immunobiology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
  • Palianina D; Department of Gene Vectors, Helmholtz Centre Munich, Munich, Germany.
  • Khanna N; Immunobiology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
  • Dirnhofer S; Immunobiology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
  • Münz C; Laboratory of Infection Biology, Department of Biomedicine, University Basel and University Hospital of Basel, Basel, Switzerland.
  • Bantug GR; Laboratory of Infection Biology, Department of Biomedicine, University Basel and University Hospital of Basel, Basel, Switzerland.
  • Hess C; Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
Science ; 385(6704): eadk4898, 2024 07 05.
Article em En | MEDLINE | ID: mdl-38781354
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos B / Transformação Celular Viral / Trifosfato de Adenosina / Herpesvirus Humano 4 / Antígenos Nucleares do Vírus Epstein-Barr / Infecções por Vírus Epstein-Barr / Indolamina-Pirrol 2,3,-Dioxigenase / NAD Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos B / Transformação Celular Viral / Trifosfato de Adenosina / Herpesvirus Humano 4 / Antígenos Nucleares do Vírus Epstein-Barr / Infecções por Vírus Epstein-Barr / Indolamina-Pirrol 2,3,-Dioxigenase / NAD Idioma: En Ano de publicação: 2024 Tipo de documento: Article