Virus-host interactions in frog virus 3 infected cells

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The research outlined in this proposal is aimed at using a scientifically unexploited but economically important virus family, the Iridoviridae, to identify novel classes of virus-host interacting genes that will help identify previously unidentified cellular anti-viral pathways. We have chosen to look at virus-host interactions in the Iridoviridae for a number of reasons. First, unlike the Herpesviridae and Poxviridae families, there is a lack of significant basic research into the biology of the Iridoviridae. Secondly, by examining new viral families, novel genes that target uncharacterized host anti-viral strategies can be identified. Finally, many Iridoviridae have been confirmed as the causative agent of severe diseases in fish and wildlife, affecting aquaculture and wildlife conservation. To understand how the Iridoviridae family circumvents host defenses, we chose frog virus 3 (FV3), the best-studied member of the Iridoviridae family, as our model system. The genomic sequence of FV3 revealed a gene, 75L that has striking homology to LITAF. 75L is an 84 amino acid protein that has sequence identity with the C-terminus of cellular LITAF, but lacks the N-terminus of LITAF. Because of the similarities between 75L and LITAF, we hypothesize that 75L interferes with LITAF's function. Specifically, we propose that 75L functions in a dominant negative fashion, antagonizing cellular LITAF function by mediating interactions through the C-terminal half of LITAF but lacking the N-terminal binding sites of LITAF. Since the role of LITAF is unknown, our research into the function of this unique cellular gene will help explain the neurodegenerative disease that is associated with mutations in LITAF, as well as advancing viral pathogenesis. Finally, the studies here will help understand how FV3 causes disease and may help management of viral outbreaks in natural populations.