Developing Hydra as a Model Organism for Viral Symbioses

描述（由申请方提供）：了解生物体、细胞和分子水平上的病毒-宿主相互作用对于减轻病毒发病机制至关重要。的目标 该项目旨在发现病毒微生物组和先天免疫在调节中的作用。 在模式生物九头蛇体内的病毒共生体通过这样做，它将确定水螅是否含有类似于人类病毒的病毒，以及测试水螅特异性基因对病毒存在的反应。水螅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，因为它们的简单的组成，它们的实验操作，和它们的上皮暴露于环境中没有保护屏障。此外，水螅缺乏适应性免疫功能，不含能动的吞噬细胞，并且仅利用粘液作为保护其上皮的手段。因此，水螅是唯一适合研究宿主-病原体相互作用的粘膜上皮。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鉴定水螅病毒群落。本研究的目的是发现与水螅相关的病毒，它们是否在应激条件下被诱导，并推断这些病毒是否参与人类的发病机制。2.）阐明水螅在胞质核酸存在下的抗病毒反应。水螅抗病毒先天免疫反应基因与人类的相似性大于苍蝇和蠕虫。因此，监测水螅先天免疫基因对病毒存在的反应将阐明病毒对上皮细胞的影响。通过实现这两个目标，导致水螅致病条件的病毒将被确定，以及病毒，类似地导致人类致病水螅内窝藏。一旦鉴定，可培养的病毒然后可以在该水螅先天免疫模型系统中进行测试。如果病原体无法培养，则将使用鉴定的病原体基因来测试水螅抗病毒识别。此外，通过鉴定对病毒感染有反应的水螅抗病毒基因，将通过基因敲低来操纵水螅，以确定哪些基因在限制病毒发病机制或促进病毒共生中至关重要。

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.