EPSTEIN-BARR VIRUS NUCLEAR ANTIGEN 1 FUCNTIONS REQUIRED IN BURKITT'S LYMPHOMAS
Document Type
Presentation
Start Date
22-10-2010 2:45 PM
End Date
22-10-2010 3:00 PM
Description
Epstein-Barr Virus (EBV) is an oncogenic human herpesvirus predominantly infecting Blymphocytes that is etiologically associated with Burkitt's lymphoma, AIDS-related immunoblastic lymphomas, post-transplant lymphoproliferative disease, nasopharyngeal carcinoma, and gastric carcinoma. Very few viral genes are expressed in these malignancies and diseases, and infectious virus is almost never released. Therefore, this type of EBV infection is called latency. Though EBNA 1 is expressed in all latency types, it does not transactivate viral genes during Type I latency, which is observed in malignancies such as Burkitt's lymphomas. In addition, a study published recently demonstrates that EBNA1 induces reactive oxygen species (ROS) when expressed in Burkitt's lymphomas, and thereby negatively affects genomic stability. EBNA1 generates ROS by increasing the expression of cytochrome b-245 heavy chain (NOX2). Because existing therapies against EBV-associated malignancies have severe limitations and may prove unsuccessful in many cases, there is a need for a more specific agent that can be utilized in all forms of viral latency. In order to design a successful therapeutic agent directed specifically against EBNA1, the domains and functions of this viral protein responsible for lymphoma development and aggression must be understood more clearly. Therefore, I have investigated the functions and domains of EBNA1 required for the aggressive proliferation of malignant Burkitt's lymphoma cells and the functions of EBNA 1 required for the detrimental activation of NOX2. This was accomplished by using a novel, dual-expression RNAi-resistant retroviral vector designed to remove endogenous EBNA1 from Burkitt's Lymphoma cells while simultaneously expressing wildtype EBNA 1 or mutants deleted in one or more domains. Using the same panel of mutants, luciferase assays were performed to identify the domains and, subsequently, their functions responsible for NOX2 overexpression. I conclude that knowing the mechanism by which EBNA 1 enhances lymphoma aggression and activates NOX2 will allow us to determine if oncogenicity can be reduced or resolved upon inhibition of this mechanism.
Recommended Citation
Washington, Amber and Aiyar, A., "EPSTEIN-BARR VIRUS NUCLEAR ANTIGEN 1 FUCNTIONS REQUIRED IN BURKITT'S LYMPHOMAS" (2010). Dr. Joseph M. Moerschbaecher, III Graduate Research Day. 8.
https://digitalscholar.lsuhsc.edu/grad_rs/2010/presentation2/8
EPSTEIN-BARR VIRUS NUCLEAR ANTIGEN 1 FUCNTIONS REQUIRED IN BURKITT'S LYMPHOMAS
Epstein-Barr Virus (EBV) is an oncogenic human herpesvirus predominantly infecting Blymphocytes that is etiologically associated with Burkitt's lymphoma, AIDS-related immunoblastic lymphomas, post-transplant lymphoproliferative disease, nasopharyngeal carcinoma, and gastric carcinoma. Very few viral genes are expressed in these malignancies and diseases, and infectious virus is almost never released. Therefore, this type of EBV infection is called latency. Though EBNA 1 is expressed in all latency types, it does not transactivate viral genes during Type I latency, which is observed in malignancies such as Burkitt's lymphomas. In addition, a study published recently demonstrates that EBNA1 induces reactive oxygen species (ROS) when expressed in Burkitt's lymphomas, and thereby negatively affects genomic stability. EBNA1 generates ROS by increasing the expression of cytochrome b-245 heavy chain (NOX2). Because existing therapies against EBV-associated malignancies have severe limitations and may prove unsuccessful in many cases, there is a need for a more specific agent that can be utilized in all forms of viral latency. In order to design a successful therapeutic agent directed specifically against EBNA1, the domains and functions of this viral protein responsible for lymphoma development and aggression must be understood more clearly. Therefore, I have investigated the functions and domains of EBNA1 required for the aggressive proliferation of malignant Burkitt's lymphoma cells and the functions of EBNA 1 required for the detrimental activation of NOX2. This was accomplished by using a novel, dual-expression RNAi-resistant retroviral vector designed to remove endogenous EBNA1 from Burkitt's Lymphoma cells while simultaneously expressing wildtype EBNA 1 or mutants deleted in one or more domains. Using the same panel of mutants, luciferase assays were performed to identify the domains and, subsequently, their functions responsible for NOX2 overexpression. I conclude that knowing the mechanism by which EBNA 1 enhances lymphoma aggression and activates NOX2 will allow us to determine if oncogenicity can be reduced or resolved upon inhibition of this mechanism.
Comments
See abstract book page 44