EBV is a ubiquitous human herpesvirus which is the etiologic agent of infection mononucleosis. EBV is also associated with a number of malignancies including Burkitt's lymphoma, Nasopharyngeal carcinoma, Oral Hairy Leukoplakia, Hodgkin's lymphoma, Adult T-cell lymphomas and lymphoproliferative diseases in transplant and AIDs patients. In vitro, EBV infects and growth transforms B lymphocytes so that they proliferate continually into lymphoblastoid cell lines (LCLs). In these infected B lymphocytes EBV expresses eleven genes one of which is the Epstein-Barr nuclear antigen (EBNA) 3C. This protein is essential for B lymphocyte transformation and there is a mounting body of evidence which demonstrates that EBNA3C is linked to cellular and viral transcription regulation by its interaction with the transcription repressor J kappa.
The specific aims of this application are (1) To determine the domains and specific amino acids of EBNA3C essential for the transformation process. (2) To identify cellular proteins interacting with EBNA3C and the critical functional domains interacting with these cellular proteins. (3) To analyze these specific interactions with cellular factors in the context of EBNA3C transcriptional activity using a transient reporter assay.
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