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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Physician Scientist Award (K11)
Project #
1K11AI000983-01
Application #
3085373
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Project Start
1990-08-01
Project End
1995-07-31
Budget Start
1990-08-01
Budget End
1991-07-31
Support Year
1
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520