Epstein-Barr virus (EBV) infects most of the world's population, is the etiological agent of Infectious mononucleosis, and is also associated with a number of malignancies including Burkitt's Lymphoma, Nasopharyngeal Carcinoma, Oral Hairy Leukoplakia, Hodgkin's Lymphoma, Adult T-Cell Lymphomas and Lymphoproliferative Diseases in AIDS patients. In vitro, EBV infects and growth transforms B-lymphocytes so that they proliferate continually into lymphoblastoid cell lines (LCLs). In these infected B-lymphocytes, EBV expresses a repertoire of latent genes. EBNA2, EBNA3A and 3C and LMP1 are essential for B lymphocyte transformation. The increase in the number of immune compromised patients in the population due to other factors like co-infection with other viral agents and genetic defects has led to an increase in the ability of EBV strains to undergo recombinantion. We propose that immune suppression provides an opportunity for selection and emergence of new EBV strains through intertypic recombination that are more potent in their ability to transform and induce proliferation of infected human cells. In this study we will investigate carcinomas and lymphomas from head and neck patients who are immune-compromised. We will specifically target samples positive for EBV based on the aggressiveness of the tumors and the immune status of the patients. The EBV genome will be analyzed for the possibility of intertypic strains of the virus from type I and type II EBV having a greater potency of transforming human B-cells. Additionally, we will create cell lines (LCLs) using the virus from these tumors to further analyze the genomes and determine the gene expression patterns of these intertypic viruses and characterize the activation markers of LCLs induced by infection with the intertypic recombinants. Finally, the new strains will be analyzed for determination of their infectivity, virulence and transformation potency. These studies will generate information for determining the potential emergence of new EBV strains in a population of immunocompromised patients with head and neck cancers and lymphomas.
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