Research - The Epstein-Barr Virus is the cause of acute infectious mononucleosis. Malignant cells from African Burkitt's lymphoma and nasopharyngeal carcinoma contain EBV genomes as do lymphocytes from many of the polyclonal B cell lymphomas currently seen in transplant recipients and among patients with AIDS. It has recently been shown that the EBVR is a 140,000 Mr cell surface glycoprotein that is identical to the receptor for the cleavage fragment of the third component of complement, C3d (CR2). The receptor whose function is unknown, is normally expressed on mature human B lymphocytes, but is absent on pre-B cells and plasma cells. It is anticipated that recombinant bacterial synthesis of the virion envelope glycoprotein(s) which mediate attachment to the receptor will form the basis of a future antitumor vaccine. During the first three years of this proposal the EBV receptor will be cloned. The cloned EBVR gene will be sequenced and evaluated. The chromosomal location of the receptor gene will be determined and its expression during differentiation will be monitored. Experiments will begin to examine the receptor for Herpesvirus Saimiri, another lymphotrophic herpesvirus expressed exclusively on primate T cells which may share conserved functions with the EBVR. The long term goal is to express and mutagenize the cloned receptor in order to study the virus-receptor interaction in detail. Candidate - The applicant's long term objective is to continue to do research and practice clinical infectious diseases in an academic setting. She completed a three-year infectious disease fellowship in July, 1983. Since that time, she has had an appointment as an Instructor at Harvard Medical School, and as a Research Fellow in the laboratory of Dr. Jack Strominger at the Dana-Farber Cancer Institute. Her primary research interest is on the nature of the EBV (C3d) receptor, and the consequences of the receptor-virus interaction. Environment - The primary sponsor's laboratory is expert in both protein biochemistry and molecular biology. These techniques have been applied in recent years to elucidation of human histocompatibility antigens and of the human T cell receptor. The laboratory of the secondary sponsor is equally expert in viral immunology and mechanisms of host-viral interaction.
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