Developing Hydra as a Model Organism for Viral Symbioses

描述(由申请人提供)：在生物、细胞和分子水平上了解病毒与宿主的相互作用对于减轻病毒致病至关重要。的目标 本项目是为了发现病毒微生物群和天然免疫在调节中的作用。 在模式生物九头蛇中的病毒共生。通过这样做，将确定九头蛇是否含有类似人类病毒的病毒，并测试九头蛇特有的基因对病毒的存在做出反应。Hydra提供了一个理想的模型来测试这些宿主-病原体的相互作用，因为它们的组成简单，易于实验操作，并且它们的上皮细胞暴露在没有保护屏障的环境中。此外，九头蛇缺乏获得性免疫功能，不包含可移动的吞噬细胞，只利用粘液作为保护其上皮的手段。因此，Hydra特别适合于研究粘膜上皮中宿主与病原体的相互作用。为此，该项目由两个具体目标组成：1.利用病毒元基因组学识别九头蛇病毒群落。这一目的是为了发现与Hydra相关的病毒，它们是否是在应激条件下诱导的，并推断这些病毒是否参与人类的发病。2.)阐明在胞质核酸存在的情况下九头蛇的抗病毒反应。与苍蝇和蠕虫相比，九头蛇特有的抗病毒先天免疫反应基因与人类具有更大的相似性。因此，监测九头蛇先天免疫基因对病毒存在的反应将澄清病毒在上皮细胞中所产生的影响。通过实现这两个目标，将识别在九头蛇中引起致病条件的病毒，以及在九头蛇中隐藏的类似导致人类发病的病毒。一旦确定，可培养的病毒就可以在这个九头蛇先天免疫模型系统中进行测试。如果病原体不能培养，识别出的病原体基因将被用于测试九头蛇抗病毒识别。此外，通过识别对病毒感染作出反应的Hydra抗病毒基因，将通过基因敲除来操纵Hydra，以确定哪些基因在限制病毒致病或促进病毒共生方面至关重要。

DESCRIPTION (provided by applicant): Understanding viral-host 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 the role of innate immunity in the regulation of viral symbioses in the model organism Hydra. By doing so, it will be determined whether Hydra contain viruses similar to human viruses as well as testing Hydra-specific genes responsive to viral presence. Hydra provide an ideal model to test these host-pathogen 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 motile phagocytic cells, and only utilize mucus as a means to preserve its epithelium. Therefore, Hydra are uniquely suited for the study of host-pathogen interactions at the mucosal epithelium. To establish this, the project consists of two specific aims: 1.) Identify Hydra viral communities utilizing viral metagenomics. The purpose of this aim is to discover the viruses associating with Hydra, whether they are induced under stress, and to deduce whether these viruses are involved in human pathogenesis. 2.) Elucidate the Hydra antiviral response in the presence of cytosolic nucleic acids. Specific Hydra antiviral innate immune response genes possess greater similarities to humans than that of flies and worms. Therefore, monitoring Hydra innate immune genes in response to viral presence will clarify the effects made by viruses at the epithelium. By accomplishing these two aims, viruses that cause pathogenic conditions in Hydra will be identified as well as viruses that similarly cause human pathogenesis harbored within Hydra. Once identified, cultivatable viruses can then be tested in this Hydra innate immunity model system. If the etiologic agent cannot be cultured, the identified agent genes will be used to test Hydra antiviral recognition. Further, by identifying the Hydra antiviral genes responsive to viral infection, Hydra will be manipulated through gene knockdown, to determine which genes are vital in either limiting viral pathogenesis or promoting viral symbiosis.