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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Physician Scientist Award (K11)
Project #
5K11CA001392-02
Application #
3085789
Study Section
Cancer Institutional Fellowship Review Committee (CT)
Project Start
1988-07-01
Project End
1993-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Mi, Shuangli; Zhang, Jian; Zhang, Wei et al. (2013) Circulating microRNAs as biomarkers for inflammatory diseases. Microrna 2:63-71
Swaminathan, S; Huneycutt, B S; Reiss, C S et al. (1992) Epstein-Barr virus-encoded small RNAs (EBERs) do not modulate interferon effects in infected lymphocytes. J Virol 66:5133-6
Swaminathan, S; Tomkinson, B; Kieff, E (1991) Recombinant Epstein-Barr virus with small RNA (EBER) genes deleted transforms lymphocytes and replicates in vitro. Proc Natl Acad Sci U S A 88:1546-50