The Epstein Barr virus is an oncogenic herpesvirus that is intimately involved in a number of malignancies in humans. The genetic basis of EBV associated oncogenesis is the concerted action of EBV latency associated genes and varying cellular genetic alterations. In immuno-competent individuals minimal EBV latency gene expression can be tolerated due to the high immunogeneticity of several of the EBV encoded latency gene products. In AIDS patients, however, expression of the full repriotrore of latency genes can sometimes be tolerated and therefore fewer cellular genetic alterations are required to give rise to malignant cell populations. This likely explains in part, the greatly increased susceptibility of AIDS patients to EBV associated non-Hodgkin's lymphomas. Unlike KSHV associated malignancies, the use of HAART therapy in AIDS patients has had a minimal influence on the number of AIDS/EBV associated non-Hodgkin's lymphomas. An array of publications in the last few years have provided compelling evidence that the small non-coding RNA genes referred to as microRNAs (miRNAs) not only play important roles in normal cellular signaling but that they are also key players in a wide array of cancers. Based on previous studies showing that EBV latency associated gene products signal through the activation of gene expression and based on the accumulating evidence indicating the role of miRNAs in cellular signaling, we hypothesize that latency associated viral gene products influence cellular miRNA gene expression. We further hypothesize that alterations in cellular miRNA expression profiles regulate key signal transduction pathways that influence the life cycle of the virus and may play a role in EBV associated oncogenesis in AIDS patients.

Public Health Relevance

EBV is associated with a number of human cancers including nasopharyngeal carcinoma, Hodgkin's disease, Burkitt's lymphoma as well as a number of B-cell lymphomas in AIDS patients. Our studies are principally aimed at addressing the role of type III viral latency gene products on cellular miRNA gene expression and how this may influence the host cell environment to facilitate the life cycle of the virus and to influence EBV mediated oncogenesis in AIDS and transplant patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA130752-05
Application #
8212350
Study Section
Special Emphasis Panel (ZRG1-AARR-C (04))
Program Officer
Daschner, Phillip J
Project Start
2008-04-01
Project End
2013-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
5
Fiscal Year
2012
Total Cost
$299,900
Indirect Cost
$98,625
Name
Tulane University
Department
Pathology
Type
Schools of Medicine
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
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