Molecular and Cellular Basis of Infection. (360G-Wellcome-097005_Z_11_Z)

EBNA3C is a viral protein expressed in human B cells that have been transformed into lymphoblastoid cell lines (LCL) by infection with Epstein-Barr virus. EBNA3C is encoded by one of three related genes (EBNA3A, EBNA3B and EBNA3C), the products of which function as transcription factors regulating host cell genes. A recent exon microarray experiment in our lab identified a small number of B cell genes whose expression is very substantially altered (up to 60-fold changes were seen) by 'switching on' a conditional EBNA3C encoded by recombinant EBV in LCLs. Several of these genes (eg COBLL1, ADAM28 and ADAMDEC1) are repressed by EBNA3C and at least one gene(AICDA) is activated by EBNA3C. We have found that COBLL1 expression is repressed just as dramatically and with similar kinetics shortly after the infection of primary B cells by EBV - indicating that the conditional EBNA3C cell system is likely to be an accurate model for the processes involved in repression during normal infection of primary B cells. . The aim of this project is to use these genes as model targets of EBNA3C and determine the molecular mechanisms underpinning the epigenetic regulation of transcription associated with this large nuclear viral protein.