Epstein-Barr virus (EBV) is a human herpes virus associated with a variety of tumors including African Burkitt lymphoma, nasopharyngeal carcinoma and immunoblastic sarcoma in immunosuppressed patients. EBV usually establishes a latent infection in B lymphocytes and stimulates them to proliferate. Sustained polyclonal proliferation of EBV infected cells in vivo may occasionally result in monoclonal malignancies. In vitro, B cells are immortalized and provide a model with which to study EBV-induced tumorigenicity. Although the EBV genome contains about 100 genes, only 10 of these are known to be expressed in latently infected, growth transformed lymphocytes. These genes are of interest because they are likely to be involved in the immortalization of lymphocytes as well as in the maintenance of viral latency. One of the genes is the EBV nuclear antigen leader protein (EBNA-LP). The function of EBNA-LP is unknown although preliminary experiments have shown that deletion of the last two exons of EBNA-LP results in a marked reduction in the growth rate of transformed cells.
The aim of the proposed studies is to determine the function of EBNA-LP. Recombinant viruses will be constructed with mutations in EBNA-LP using techniques which our laboratory has used successfully to construct recombinant EBV with mutations in the EBNA2 gene. We then will determine if the mutations in EBNA-LP alter growth rate, RNA metabolism or protein expression of cells transformed by EBV. Finally we will analyze whether transfection of wild-type EBNA-LP into cells expressing mutant EBNA-LP can recreate a wild type phenotype, thus confirming that alterations in phenotype are due to the EBNA-LP mutations. Elucidation of the function of EBNA-LP will lead to a better understanding of EBV-induced transformation which in turn may increase our understanding of oncogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Physician Scientist Award (K11)
Project #
5K11AI000996-05
Application #
2057015
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Project Start
1990-09-30
Project End
1995-08-31
Budget Start
1994-09-01
Budget End
1995-08-31
Support Year
5
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Harvard University
Department
Surgery
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115