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Research Interests:
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The research in our laboratory encompasses efforts to understand the pathogenesis of arboviruses, particularly those associated with hemorrhagic fevers in humans. The viruses that we utilize for our research include the flaviviruses yellow fever virus and Omsk hemorrhagic fever virus. We utilize these virus models as both provide unique opportunities to examine specific mechanisms of pathogenesis.
Yellow fever virus, the first recognized hemorrhagic fever virus, affects an estimated 200,000 people annually, making it the most prolific of all hemorrhagic fevers. The existence of a live attenuated vaccine strain for yellow fever allows us to compare the disease caused by the wild-type virus to the infection caused by the vaccine strain. We have established that the infection of HUVECs with either strain results in a variable cytokine response following infection which suggests that endothelial cells may play a role in propagation of the virus during infection and may also play a significant role in the increased severity of infection by wild-type virus. This variable cytokine response is hypothesized to directly affect the susceptibility of other cells or tissues to infection and to stimulate the release of acute phase proteins from the liver. It is also hypothesized that infection with wild-type virus plays a significant role in affecting the permeability of the vascular endothelium which would contribute to vascular leakage. We are currently examining a number of different aspects of yellow fever virus infection in cell culture so that we can test their role during the course of disease in the hamster model. We will use the finding from this work for the development of therapies for the treatment of yellow fever infection.
Omsk hemorrhagic fever virus (OHFV) is a tick-borne flavivirus found in a localized region of Siberia. While this virus does not present a significant health risk to the United States or the population at-large, it does provide a unique opportunity to determine which host or viral factors play a role in determining whether a virus causes an encephalitic disease or hemorrhagic fever. We have developed a mouse model for OHFV and shown that the disease caused in this model is quite a bit different that that caused by other tick-borne flaviviruses despite significant genetic similarity. We are currently examining the pathogenicity of OHFV and a strain of Far-eastern tick-borne encephalitis virus in cell culture and in the mouse model. The objective of this research is to identify components of the host immune response that may play a role in dictating whether a virus gains access to the central nervous system. We are also examining several other factors that may play a role in a viruses ability to breach the blood-brain barrier. As with our work with yellow fever virus, the objective of this research is to utilize the results of our work for the development of therapeutics to combat viral infection.
Our studies include both mosquito- and tick-borne flaviviruses in the study of viral hemorrhagic fevers. The use of viruses that include different arthropod vectors in their “life" cycle will provide the opportunity to compare the potential role of vector specific factors in disease. The flaviviruses also represent only a few of the known viruses that cause hemorrhagic fever. We believe that these model systems will provide fundamental information that can be incorporated into studies with arenaviruses or filoviruses. The BSL-4 facilities available at UTMB will allow us to test our findings with OHFV or yellow fever virus in other viral systems as well.
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