The objective of the proposed project is to evaluate the cellular immune response to Rift Valley fever virus (RVFV) wild-type (ZH501) and vaccine strain (MP-12) infections. There is very little published data pertaining to the effect of RVFV infection on the host cellular immune response. RVFV is a very important human pathogen and it is listed as a Category A agent on the NIAID list of priority pathogens. RVFV is also a significant agricultural risk as the virus causes severe disease in ruminants. In outbreaks, there is a nearly 100% abortion rate in infected pregnant livestock and a 5%-60% mortality rate in adult animals. During outbreaks, this virus infects humans and in some cases results in severe disease and potentially death in the form of encephalitis or hemorrhagic fever. Even though RVFV is a typically transmitted by mosquitoes, there is evidence suggesting that RVFV can be transmitted by aerosol. My preliminary efforts to characterize the effect of MP-12 infection on cellular immunity in mice have found that the MP-12 vaccine strain can significantly inhibit Th1 associated cytokines including interferon-? and Th1 associated proinflammatory cytokines. Furthermore, I have found that the phosphorylation of the pro-apoptotic proteins examined to date show an increase when comparing uninfected cells to infected cells. These data point to a distinct mechanism for inhibiting the host response to viral infection in mice;however, the MP-12 vaccine strain does not cause lethal disease in mice while the wild-type virus is highly lethal to mice. The long-term goal of this project is to differentiate the host response to infection by wild-type and vaccine strains of RVFV in an effort to identify specific mechanisms associated with disease pathogenesis. My hypothesis is that there is a marked difference in phosphoprotein expression that can be correlated with cytokine induction between RVFV and MP-12 infections and this difference can be associated with disease pathogenesis. Both of these infections should result in a decrease of pro-inflammatory and Th1 cytokines and the increase of various pro-apoptotic phosphoproteins. With a better understanding of the host response to RVFV infection, we will be able to pursue intelligently designed vaccines and therapeutics that stimulate a protective immune response without potentially deleterious effects that could lead to encephalitis or hemorrhagic disease. Relevance: This project will lead to a better understanding of how the immnune system interacts with RVFV. By knowing how the host protects itself it will be possible to create better vaccanies and treatments that will be available after infection by the virus. Since very little is known about cellular response in RVFV infections, a foundation needs to be laid that can be built upon in the future in the case of treatment and vaccines.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZRG1-DIG-E (29))
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Adger-Johnson, Diane S
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University of Texas Medical Br Galveston
Schools of Medicine
United States
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Roberts, Kimberly K; Hill, Terence E; Davis, Melissa N et al. (2015) Cytokine response in mouse bone marrow derived macrophages after infection with pathogenic and non-pathogenic Rift Valley fever virus. J Gen Virol 96:1651-1663
Gray, Kimberly K; Worthy, Melissa N; Juelich, Terry L et al. (2012) Chemotactic and inflammatory responses in the liver and brain are associated with pathogenesis of Rift Valley fever virus infection in the mouse. PLoS Negl Trop Dis 6:e1529