Dissecting and disrupting Epstein-Barr virus transcription initiation and elongation during latent infection. (360G-Wellcome-078291_Z_05_Z)

This research will test the hypothesis that the switch from W to C promoter usage during initial EBV infection represents a switch from non-processive transcription to EBNA 2-activated CDK9-dependent processive transcription necessary for the efficient production of the long primary transcript and the establishment of latency. We will also investigate whether the requirement for CDK9 for the efficient activation of transcription by EBNA 2 makes the anti-cancer drug and CDK9 inhibitor, Flavopiridol, an effective anti-EBV agent. Additional studies will further dissect the way in which pol II phosphorylation is regulated by EBNA 2. Key goals 1. Determine whether EBNA 2 stimulates transcriptional elongation in addition to initiation. 2. Determine whether EBNA 2 activated transcription can be blocked using Flavopiridol. 3. Dissect how pol II phosphorylation is regulated by EBNA 2.