Epstein-Barr virus, (EBV), is believed to be an etiologic agent of Burkitt's lymphoma, nasopharyngeal carcinoma, and B cell lymphomas in immunocompromised patients. EBV is capable of immortalizing B cells, enabling them to proliferate in vitro. A limited repertoire of EBV genes is expressed in such transformed cells, as well as in EBV-infected Burkitt's lymphoma cells. The roles of these genes in inducing cell proliferation and maintaining latent infection is currently under investigation. The mechanisms by which the expression of these EBV genes is controlled are poorly understood. These control mechanisms are central to maintaining latent EBV infection and cell immortalization. The specific goals of this goals of this project are to investigate the role of two small molecular weight RNAs synthesized in large amounts in EBV-transformed cells, (EBV-encoded RNA: EBER 1 and EBER 2), in the transcriptional and translational regulation of other latent-cycle genes. The EBERs are functionally and structurally similar to adenovirus-associated RNAs (VA RNAs), which are known to be essential for translational and transcriptional control in adenovirus infection. The EBER genes will be introduced into B cell lines, along with one or more of the EBV genes expressed in latent infection. This will allow analysis of the effects of EBER RNA on the expression of the genes necessary for cell transformation. At least two of the proteins expressed in latent infection are translated from a bicistronic mRNA. This investigation will also analyze the role of EBER RNA in the translation of this unusual mRNA. This could provide further insights into a mechanism of regulation of eukaryotic protein translation.
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