Cover Image

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

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...

Full description

Saved in:
Bibliographic Details
Main Authors: Sommermann, Thomas (Author) , Yasuda, Tomoharu (Author) , Ronen, Jonathan (Author) , Wirtz, Tristan (Author) , Weber, Timm (Author) , Sack, Ulrike (Author) , Caeser, Rebecca (Author) , Zhang, Jingwei (Author) , Li, Xun (Author) , Chu, Van Trung (Author) , Jauch, Anna (Author) , Unger, Kristian (Author) , Hodson, Daniel J. (Author) , Akalin, Altuna (Author) , Rajewsky, Klaus (Author)
Format: Article (Journal)
Language:English
Published: June 10, 2020
In: Proceedings of the National Academy of Sciences of the United States of America
Year: 2020, Volume: 117, Issue: 25, Pages: 14421-14432
ISSN:1091-6490
DOI:10.1073/pnas.1921139117
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1073/pnas.1921139117
Get full text
Author Notes:Thomas Sommermann, Tomoharu Yasuda, Jonathan Ronen, Tristan Wirtz, Timm Weber, Ulrike Sack, Rebecca Caeser, Jingwei Zhang, Xun Li, Van Trung Chu, Anna Jauch, Kristian Unger, Daniel J. Hodson, Altuna Akalin, and Klaus Rajewsky
Description
Summary: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.
Item Description:Gesehen am 09.09.2020
Physical Description:Online Resource
ISSN:1091-6490
DOI:10.1073/pnas.1921139117

Similar Items