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

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Item Type:	Article
Title:	Functional interplay of Epstein-Barr virus oncoproteins in a mouse model of B cell lymphomagenesis
Creators Name:	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. 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
Additional Information:	Published under the PNAS license. https://www.pnas.org/authors/fees-and-licenses . Copyright © 2020, The Author(s), under exclusive licence to publish to PNAS.
Official Publication:	https://doi.org/10.1073/pnas.1921139117
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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