Ehrlich, Elana S.Chmura, Jennifer2015-12-172015-12-172014-07-102014-05TSP2014Chmurahttp://hdl.handle.net/11603/2004(M.S.) -- Towson University, 2014.Kaposi's sarcoma-associated herpesvirus (KSHV) is a gamma-2 herpesvirus that causes lymphoid and endothelial tumors through establishing two replication states: latent and lytic. Latency is maintained in part through expression of viral FLICE inhibitory protein (vFLIP) which inhibits apoptosis and activates nuclear factor-kappaB (NF-KB) signaling. Lytic replication is dependent on the major transactivator of lytic gene expression, replication and transcription activator protein (RTA). vFLIP or NF-KB inhibition results in lytic reactivation, suggesting RTA may have a role in vFLIP stability. Data show RTA destabilizes vFLIP and inhibits vFLIP-induced NF-KB signaling by inducing ubiquitin-proteasome-mediated vFLIP degradation. This thesis provides evidence that the ubiquitin E3-ligase activities of Itch and A20, but not RTA, are required for vFLIP degradation. Immunoprecipitation evidence of A20, Itch, RTA, and vFLIP interaction suggests RTA interacts with the A20/Itch ubiquitin-editing complex to induce vFLIP degradation, inhibiting NF-KB signaling and allowing for lytic reactivation.application/pdfv, 52 pagesengCopyright protected, all rights reserved.Text