The purpose of this study is to determine whether the Epstein-Barr Virus (EBV) genome interacts with the host nuclear matrix in order to coordinate viral DNA replication, genome segregation and gene expression. EBV is a human herpesvirus that primarily infects B-lymphocytes and can establish a latent viral life cycle within the host cell. Mono- and polyclonal B-cell proliferations result from immortalization of infected cells and are a cause of morbidity and mortality primarily in immunosuppressed patients. EBV is a 17U kb double stranded DNA virus which exists as a supercoiled episome with the host nucleus and utilizes host replication and transcription machinery. The nuclear matrix is a dynamic proteinaceous nuclear substructure. It packages the DNA and provides a higher level of organization in the nucleus so that transcription and replication can be performed in an efficient manner. Similarly, this level of organization may be required to maintain EBV latency. Replication of EBV DNA must be coordinate with host cell replication, the EBV episome must segregate upon cell division and transcription of latency-specific viral genes must occur. Interactions of the EBV episome with the host nuclear matrix could coordinate the maintenance of the latent state. This study will determine whether the EBV episome associates the host nuclear matrix in a sequence-specific manner. It is important to ascertain whether this interaction varies in a virus and/or cell cycle dependent fashion. Furthermore, it has recently been shown that EBNA-1, the predominant viral latent protein, binds to the EBV origin of plasmid replication. Therefore, EBNA-1 may be involved in the binding of the viral episome to the nuclear matrix. It is important to understand the nature of the interactions of the EBV episome with the nuclear matrix in order to develop antiviral agents against EBV.
| Jankelevich, S; Kolman, J L; Bodnar, J W et al. (1992) A nuclear matrix attachment region organizes the Epstein-Barr viral plasmid in Raji cells into a single DNA domain. EMBO J 11:1165-76 |
