Virus-host interactions in frog virus 3

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Background: The overarching goal of my research program is to explore virus-host interactions in frog virus 3 (FV3), a member of the Ranavirus genus of the Iridoviridae family. Ranaviruses are of concern because of their impact on amphibian communities. Amphibian populations are globally threatened with 43% of amphibians demonstrating population declines. One factor contributing to amphibian declines are Ranaviruses. Our lab has been studying FV3 to understand the basic biology of the virus, as well as characterizing how FV3 impacts amphibian populations. To understand mechanisms of pathogenesis and innate immune defenses our lab will explore two parallel ways in which viruses interact with a host cell. One area of investigation explores virus-host protein-protein interactions, the other area studies defences based on small signalling molecules. Hypothesis: We hypothesize that the FV3 gene 97R and cytokinin hormones modulate host defense mechanisms in the cell. Specifically, we will identify and characterize binding partners of FV3 97R. We will also determine what role cytokinins play in vertebrate viral infections. To achieve these goals, we propose to: 1)Establish the role that prohibitin-1 plays during FV3 infections. We demonstrated that the FV3 gene 97R binds to prohibitin-1. We will determine whether the 97R/prohibitin-1 interaction plays a biological role in an FV3 infection, perhaps modulating the cell death pathways in the cell. 2)Ascertain whether endogenous cytokinins are altered in viral infections. Cytokinins are hormones that carry out a variety of roles in plants. We will explore whether an FV3 infection alters the production of cytokinin's by the host cell and if so, what biological pathways are involved. 3)Determine if exogenous cytokinins inhibit viral infections. We have shown that cytokinin's can inhibit an FV3 infection. We propose to determine what stage of the FV3 replication cycle is inhibited as well as determining the full complement of cytokinin's that inhibit FV3 replication. Significance: The research outlined in this proposal is aimed at using a scientifically unexploited but economically important virus family, the Iridoviridae, to explore novel anti-viral strategies, provide new insight into the function of the host immune system, and understand how virus-host interactions lead to viral pathogenesis. This proposal focuses on FV3 97R and its interactions with prohibitin-1, which may shed light on a novel virus-host interaction. In addition, although cytokinin hormones are well documented in plants, their roles in vertebrate systems remain largely unknown. Characterizing cytokinins in vertebrates will provide a better understanding of basic biology and may reveal an uncharacterized host defense mechanism. Ultimately, these studies will help understand how FV3 causes disease and may help management of viral outbreaks in natural populations.