Date of Defense
7-11-2024 1:30 PM
Location
Yanah Theatre
Document Type
Thesis Defense
Degree Name
Master of Medical Sciences (Microbiology and Immunology)
College
CMHS
Department
Medical Microbiology and Immunology
First Advisor
Prof. Gulfaraz Khan
Keywords
Primary EBV infection; rabbit model; oral vs IV infection; viral latency and reactivation; cellular targets of EBV.
Abstract
The isolation of Epstein-Barr Virus (EBV) in 1964 from a case of Burkitt lymphoma prompted a surge in research on the biology of this oncogenic virus and its role in the pathogenesis of associated malignancies. Over half a century later, a number of pertinent questions on the dynamics of EBV and the cellular targets of primary infection remain poorly defined. One major obstacle in EBV research has been the lack of a suitable small animal model. EBV is a highly human tropic virus. We have recently established a novel rabbit model of EBV infection that appears to mimic natural infection in humans. This research aimed to compare the oral versus intravenous (IV) mode of EBV transmission, the degree of viral spread in blood and peripheral organs, long-term latency, and viral reactivation. Specifically, the study explored whether oral transmission of EBV is as effective as blood-borne transmission. We investigated the connection between the transmission mode and the extent of viral dissemination in the peripheral organs and the blood. We also examined if the transmission mode influences long-term viral latency and reactivation following immunosuppression. A sample of 34 rabbits was randomly divided into three groups (IV: 15 rabbits, oral: 15 rabbits and controls: 4 rabbits) to address these research questions. Both groups received the same quantity of fresh cell culture-derived EBV via oral or intravenous route. Using histology, PCR/qPCR, EBER-in situ hybridization, and immunohistochemistry, our investigations indicated that rabbits can be infected with EBV via both oral and IV routes of transmission. However, the oral transmission mode is less efficient than the intravenous route. Moreover, immunosuppression of latently EBV-infected rabbits resulted in the reactivation of the virus. The viral load was lower in an oral group compared with the IV. This was also reflected in the degree of viral dissemination in other organs, most notably, the spleen. The rabbit model of EBV infection holds great potential for unraveling the biology of EBV and its associated diseases. In this study, we show that the mode of transmission impacts EBV's long-term latency and reactivation.
Included in
Immune System Diseases Commons, Medical Immunology Commons, Medical Microbiology Commons
USING A RABBIT MODEL TO UNDERSTAND THE IMPACT OF ORAL VERSUS INTRAVENOUS TRANSMISSION OF EPSTEIN-BARR VIRUS
Yanah Theatre
The isolation of Epstein-Barr Virus (EBV) in 1964 from a case of Burkitt lymphoma prompted a surge in research on the biology of this oncogenic virus and its role in the pathogenesis of associated malignancies. Over half a century later, a number of pertinent questions on the dynamics of EBV and the cellular targets of primary infection remain poorly defined. One major obstacle in EBV research has been the lack of a suitable small animal model. EBV is a highly human tropic virus. We have recently established a novel rabbit model of EBV infection that appears to mimic natural infection in humans. This research aimed to compare the oral versus intravenous (IV) mode of EBV transmission, the degree of viral spread in blood and peripheral organs, long-term latency, and viral reactivation. Specifically, the study explored whether oral transmission of EBV is as effective as blood-borne transmission. We investigated the connection between the transmission mode and the extent of viral dissemination in the peripheral organs and the blood. We also examined if the transmission mode influences long-term viral latency and reactivation following immunosuppression. A sample of 34 rabbits was randomly divided into three groups (IV: 15 rabbits, oral: 15 rabbits and controls: 4 rabbits) to address these research questions. Both groups received the same quantity of fresh cell culture-derived EBV via oral or intravenous route. Using histology, PCR/qPCR, EBER-in situ hybridization, and immunohistochemistry, our investigations indicated that rabbits can be infected with EBV via both oral and IV routes of transmission. However, the oral transmission mode is less efficient than the intravenous route. Moreover, immunosuppression of latently EBV-infected rabbits resulted in the reactivation of the virus. The viral load was lower in an oral group compared with the IV. This was also reflected in the degree of viral dissemination in other organs, most notably, the spleen. The rabbit model of EBV infection holds great potential for unraveling the biology of EBV and its associated diseases. In this study, we show that the mode of transmission impacts EBV's long-term latency and reactivation.