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

Item Type:Article
Title:Functional interplay of Epstein-Barr virus oncoproteins in a mouse model of B cell lymphomagenesis
Creators Name:Sommermann, T. and Yasuda, T. and Ronen, J. and Wirtz, T. and Weber, T. and Sack, U. and Caeser, R. and Zhang, J. and Li, X. and Chu, V.T. and Jauch, A. and Unger, K. and Hodson, D.J. and Akalin, A. and Rajewsky, K.
Abstract: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.
Keywords:Epstein-Barr Virus, LMP1, EBNA, B Cell Lymphomagenesis, Plasma Cell Differentiation, Animals, Mice
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences
Volume:117
Number:25
Page Range:14421-14432
Date:23 June 2020
Official Publication:https://doi.org/10.1073/pnas.1921139117
PubMed:View item in PubMed

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