Ricerc@Sapienza

The early phase of Epstein-Barr-Virus (EBV) lytic cycle is characterized by translocation of viral capsid from nucleus to cytoplasm, a process called nuclear egress. We already identified and characterized two EBV proteins required for this process called BFRF1 and BFLF2. BFRF1 interacts with BFLF2 and with nuclear lamin B to form the nuclear egress complex (NEC), moreover it is able to dislocate emerin, an integral nuclear membrane protein that binds nuclear lamina (NL) and is involved in wide range of functions including gene regulation, cell signaling, nuclear and genomic architectural organization. Aim of this project is to investigate if EBV NEC interacts with other cellular proteins involved in nuclear membrane dynamics and the impact of these interactions on EBV nuclear egress as well as on cellular processes . One of these proteins is BAF (Barrier to autointegration factor), we hypothesized that it might mediate viral genome targeting to the NL and the subsequent packaging since it is able to bridge chromosomes to the NL. Moreover we should like to investigate the influence of EBV lytic cycle on LINC complex, a structure localized on the nuclear membrane strictly associated to cytoskeleton, whose signaling is critical for determining cell shape, migration and differentiation. These nuclear structural alterations are strongly associated with various severe human diseases including cancer and increasing evidence reveals that Herpesviruses lytic cycle also plays an important role in the carcinogenic process. Finally the study of these viral-nuclear interactions besides representing a progress in understanding viral biology could shed light on mechanisms important for viral carcinogenesis and could provide a useful model for NL associated pathologies.