The mechanisms of EBV-induced B cell activation and transformation are under intensive investigation, but are as yet poorly understood. In this proposal we will (a) attempt to reconstitute the transformed phenotype by determining which constellation of EBV genes are necessary and sufficient to transform B cells, and (b) determine whether B cell growth factors can replace the function provided by individual EBV genes. By using the techniques of mutagenesis, we will try to locate functional domains of EBV proteins which are responsible for B cell activation and transformation. These findings should ultimately provide information regarding the mechanisms of viral transformation and oncogenesis. In addition, further knowledge of EBV-induced B cell activation may provide insights into normal B cell activation by antigens and accessory T cells. These findings may lead to new therapeutic modalities for EBV associated cancers and to new strategies for modulation of normal B cell growth and activation in vivo and in vitro. The candidate is currently a fellow in the Department of Infectious Diseases at the Beth Israel and Brigham and Women's Hospitals. He completed an internship and residency in internal medicine and performed research at the NIH on viral hepatitis. At the time of the award, he will have completed the clinical portion of a fellowship in infectious diseases. Research will be performed in the laboratory of Dr. Elliott Kieff at the Department of Microbiology and Molecular Genetics of Harvard Medical School. The laboratory is presently engaged in molecular biology studies of Epstein-Barr virus. Additional facilities in the Department of Microbiology are available.
| Cohen, J I; Wang, F; Kieff, E (1991) Epstein-Barr virus nuclear protein 2 mutations define essential domains for transformation and transactivation. J Virol 65:2545-54 |
| Wang, F; Tsang, S F; Kurilla, M G et al. (1990) Epstein-Barr virus nuclear antigen 2 transactivates latent membrane protein LMP1. J Virol 64:3407-16 |
| Young, L; Alfieri, C; Hennessy, K et al. (1989) Expression of Epstein-Barr virus transformation-associated genes in tissues of patients with EBV lymphoproliferative disease. N Engl J Med 321:1080-5 |
| Cohen, J I; Wang, F; Mannick, J et al. (1989) Epstein-Barr virus nuclear protein 2 is a key determinant of lymphocyte transformation. Proc Natl Acad Sci U S A 86:9558-62 |
