Understanding host-viral interactions at the organismal, cellular, and molecular levels are vital in mitigating viral pathogenesis. The goals of this project are to discover the viral microbiome and specific antiviral immunity genes in the model organism Hydra. By doing so, we will determine whether Hydra contains viruses similar to human viruses as well as being able to test Hydra specific immunity genes responsive to viral presence. Hydra provides an ideal model to test these host-viral interactions because of their simplistic composition, their ease of experimental manipulation, and their epithelial exposure to the environment without a protective barrier. Further, Hydra lack adaptive immunity features, do not contain any motile phagocytic cells, and only utilize mucous as a means to preserve its epithelium. Therefore, Hydra is uniquely suited for the study of host-viral innate immunity at the mucosal epithelium. To establish this, the project consists of two specific aims: 1.) Determine the Hydra viral composition utilizing viral metagenomics. 2.) Elucidate the Hydra antiviral innate immune response in the presence of cytosolic nucleic acids. By accomplishing these two aims we will identify viruses that cause pathogenic conditions in Hydra as well as discern viruses that similarly cause human pathogenesis. These viruses can then be tested in this innate immunity model system. Further, by identifying the Hydra antiviral genes responsive to viral infection, we will manipulate the Hydra through gene knockdown, to determine which genes are vital in limiting viral pathogenesis.
Establishing Hydra as an antiviral mucosal innate immunity model organism is important for human health as demonstrated by genetic variants in phylogenetically ancient innate immune genes are involved in the etiology of chronic inflammatory diseases of the epithelial barrier, such as Crohn's disease, atopic dermatitis, and asthma. These polygenic diseases are characterized by chronic relapsing inflammation of the mucosa. Such disease states and the response to them can be studied in the Hydra model system.
|Barr, Jeremy J; Auro, Rita; Sam-Soon, Nicholas et al. (2015) Subdiffusive motion of bacteriophage in mucosal surfaces increases the frequency of bacterial encounters. Proc Natl Acad Sci U S A 112:13675-80|
|Quistad, Steven D; Stotland, Aleksandr; Barott, Katie L et al. (2014) Evolution of TNF-induced apoptosis reveals 550 My of functional conservation. Proc Natl Acad Sci U S A 111:9567-72|
|Grasis, Juris A; Lachnit, Tim; Anton-Erxleben, Friederike et al. (2014) Species-specific viromes in the ancestral holobiont Hydra. PLoS One 9:e109952|
|Barr, Jeremy J; Auro, Rita; Furlan, Mike et al. (2013) Bacteriophage adhering to mucus provide a non-host-derived immunity. Proc Natl Acad Sci U S A 110:10771-6|