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Müller-Durovic, B.* ; Jäger, J.* ; Engelmann, C.* ; Schuhmachers, P.* ; Altermatt, S.* ; Schlup, Y.* ; Duthaler, U.* ; Makowiec, C.* ; Unterstab, G.* ; Roffeis, S.* ; Xhafa, E.* ; Assmann, N.* ; Trulsson, F.* ; Steiner, R.* ; Edwards-Hicks, J.* ; West, J.* ; Turner, L.* ; Develioglu, L.* ; Ivanek, R.* ; Azzi, T.* ; Dehio, P.* ; Berger, C.* ; Kuzmin, D.* ; Saboz, S.* ; Mautner, J. ; Löliger, J.* ; Geigges, M.* ; Palianina, D.* ; Khanna, N.* ; Dirnhofer, S.* ; Münz, C.* ; Bantug, G.R.* ; Hess, C.* ; Koller, M.* ; Rossi, S.* ; Stampf, S.* ; Müller, N.J.*

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

Science 385:eadk4898 (2024)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 0036-8075
e-ISSN 1095-9203
Journal Science
Quellenangaben Volume: 385, Issue: 6704, Pages: , Article Number: eadk4898 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)