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Sommermann, T.* ; Yasuda, T.* ; Ronen, J.* ; Wirtz, T.* ; Weber, T.* ; Sack, U.* ; Caeser, R.* ; Zhang, J.* ; Li, X.* ; Chu, V.T.* ; Jauch, A.* ; Unger, K. ; Hodson, D.J.* ; Akalin, A.* ; Rajewsky, K.*

Functional interplay of Epstein -Barr virus oncoproteins in a mouse model of B cell.

Proc. Natl. Acad. Sci. U.S.A. 117, 14421-14432 (2020)
Publ. Version/Full Text Postprint DOI PMC
Epstein-Barr virus (EBV) is a B cell transforming virus that causes B cell malignancies under conditions of immune suppression. EBV orchestrates B cell transformation through its latent membrane proteins (LMPs) and Epstein-Barr nuclear antigens (EBNAs). We here identify secondary mutations in mouse B cell lymphomas induced by LMP1, to predict and identify key functions of other EBV genes during transformation. We find aberrant activation of early B cell factor 1 (EBF1) to promote transformation of LMP1-expressing B cells by inhibiting their differentiation to plasma cells. EBV EBNA3A phenocopies EBF1 activities in LMP1-expressing B cells, promoting transformation while inhibiting differentiation. In cells expressing LMP1 together with LMP2A, EBNA3A only promotes lymphomagenesis when the EBNA2 target Myc is also overexpressed. Collectively, our data support a model where proproliferative activities of LMP1, LMP2A, and EBNA2 in combination with EBNA3A-mediated inhibition of terminal plasma cell differentiation critically control EBV-mediated B cell lymphomagenesis.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Epstein-barr Virus ; Lmp1 ; Ebna ; B Cell Lymphomagenesis ; Plasma Cell Differentiation; Nf-kappa-b; Tumor-suppressor; Lymphoproliferative Disorders; Nuclear Antigen-1; Genome-wide; In-vivo; C-rel; Ebv; Expression; Lymphoma
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Journal Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Volume: 117, Issue: 25, Pages: 14421-14432 Article Number: , Supplement: ,
Publisher National Academy of Sciences
Publishing Place 2101 Constitution Ave Nw, Washington, Dc 20418 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Translational Metabolic Oncology (TMO)