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

Thomas Sommermann | Zendy; Tomoharu Yasuda | Zendy; Jonathan Ronen | Zendy; Tristan Wirtz | Zendy; Timm Weber | Zendy; Ulrike Sack | Zendy; Rebecca Caeser | Zendy; Jingwei Zhang | Zendy; Xun Li | Zendy; Van Trung Chu | Zendy; Anna Jauch | Zendy; Kristian Unger | Zendy; Daniel J. Hodson | Zendy; Altuna Akalin | Zendy; Klaus Rajewsky | Zendy

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

Author(s) -

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,

Klaus Rajewsky

Publication year - 2020

Publication title -

proceedings of the national academy of sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.011

H-Index - 771

eISSN - 1091-6490

pISSN - 0027-8424

DOI - 10.1073/pnas.1921139117

Subject(s) - epstein–barr virus , biology , b cell , virus , cell , cancer research , phenocopy , virology , microbiology and biotechnology , gene , immunology , antibody , genetics , phenotype

Significance Epstein-Barr virus (EBV) efficiently transforms human B cells and causes B cell lymphomagenesis especially in immunocompromised patients. We study this process in genetically engineered mice to untangle the interplay of EBV oncogenes. We find Epstein-Barr nuclear antigen (EBNA) 3A to have both oncogenic and tumor suppressive roles. First, EBNA3A promotes B cell transformation by inhibiting LMP-driven plasma cell differentiation, a function which can be mimicked by aberrant activation of early B cell factor 1 (EBF1). Second, EBNA3A blunts Myc-driven proliferation, rendering B cell transformation dependent on Myc activation by the EBV protein EBNA2. The presented mouse model thus highlights the role of EBV oncogenes in orchestrating B cell transformation through control of B cell differentiation and Myc levels.

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