Hydra as an Antiviral Innate Immunity Model System

描述（由申请方提供）：了解生物体、细胞和分子水平上的宿主-病毒相互作用对于减轻病毒发病机制至关重要。该项目的目标是发现模式生物水螅中的病毒微生物组和特异性抗病毒免疫基因。通过这样做，我们将确定水螅是否含有类似于人类病毒的病毒，以及能够测试水螅特异性免疫基因对病毒存在的反应。Hydra提供了一个理想的模型来测试这些宿主-病毒相互作用，因为它们的组成简单，易于实验操作，并且它们的上皮暴露于环境中而没有保护屏障。此外，水螅缺乏适应性免疫功能，不包含任何能动的吞噬细胞，并且仅利用粘液作为保护其上皮的手段。因此，Hydra是唯一适合于粘膜上皮的宿主病毒先天免疫的研究。为了实现这一目标，该项目包括两个具体目标：1。利用病毒宏基因组学确定水螅病毒组成。2.）的情况。阐明水螅抗病毒天然免疫反应在胞质核酸的存在。通过实现这两个目标，我们将确定导致水螅致病条件的病毒，以及辨别病毒，同样导致人类发病。然后可以在这种先天免疫模型系统中测试这些病毒。此外，通过鉴定水螅抗病毒基因对病毒感染的反应，我们将操纵水螅通过基因敲低，以确定哪些基因是至关重要的限制病毒的发病机制。 公共卫生相关性：将水螅建立为抗病毒粘膜先天免疫模式生物体对于人类健康是重要的，如通过遗传学上古老的先天免疫基因中的遗传变体所证明的，所述遗传学上古老的先天免疫基因参与上皮屏障的慢性炎性疾病（例如克罗恩病、特应性皮炎和哮喘）的病因学。这些多基因疾病的特征在于粘膜的慢性复发性炎症。这种疾病状态和对它们的反应可以在Hydra模型系统中进行研究。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.