Epstein-Barr virus protein EBNA-LP engages YY1 through leucine-rich motifs to promote naïve B cell transformation.

Epstein-Barr Virus (EBV) is associated with various B cell lymphomas, particularly in immunosuppressed individuals. In the absence of a functional immune system, viral latency proteins, including EBV Nuclear Antigens (EBNAs) act as oncoproteins to promote tumorigenesis. EBNA-LP is one of the first viral proteins produced after infection and is important for the transformation of naïve B cells. However, the roles of EBNA-LP during infection are largely undefined. In this study, developed an assay in which the role of wild type and mutant EBNA-LP could be investigated in context of primary naïve B cells infected with an EBNA-LP Knock Out virus. Using this assay, we identified highly conserved leucine-rich motifs within EBNA-LP that are important for transformation of EBV-infected naïve B cells. These conserved motifs associate with the cellular transcription factor YY1, an important transcriptional regulator in B cell development and in many cancers, that we now show is essential for outgrowth of EBV infected B cells. Our study provides further insights into the mechanisms by which EBV transforms naïve B cells.