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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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