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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,6,23]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1073\/pnas.1921139117","type":"journal-article","created":{"date-parts":[[2020,6,10]],"date-time":"2020-06-10T20:15:31Z","timestamp":1591820131000},"page":"14421-14432","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":28,"title":["Functional interplay of Epstein-Barr virus oncoproteins in a mouse model of B cell lymphomagenesis"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2899-0256","authenticated-orcid":false,"given":"Thomas","family":"Sommermann","sequence":"first","affiliation":[{"name":"Department of Cancer Research, Max Delbr\u00fcck Center for Molecular Medicine, 13215 Berlin, 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