Hydra as an Antiviral Innate Immunity Model System

Hydra 作为抗病毒先天免疫模型系统

• 批准号: 8233283
• 负责人: FOREST L ROHWER
• 金额: $ 18.69万
• 依托单位: SAN DIEGO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8233283
• 关键词: Animal Model; Antiviral Agents; Antiviral Response; Asthma; Atopic Dermatitis; Biological Models; Chronic; Crohn' s disease; DNA; Disease; Environment; Epithelial; Epithelium; Etiology; Exposure to; Filtration; Flowcharts; Genes; Goals; Health; Housing; Human; Human Virus; Hydra Polyps; Immune; Immune response; Immunity; In Vitro; Inflammation; Inflammatory; Interferons; Life; Metagenomics; Modeling; Molecular; Monitor; Mucous Membrane; Mucous body substance; Natural Immunity; Nucleic Acids; Pathogenesis; Pathway interactions; Phagocytes; RNA; RNA Interference; Receptor Gene; Relapse; Reverse Transcriptase Polymerase Chain Reaction; Satellite Viruses; Small Interfering RNA; Stimulus; Testing; Up-Regulation; Viral; Viral Pathogenesis; Virus; Virus Diseases; adaptive immunity; cesium chloride; genetic variant; knock-down; metagenome; microbiome; particle; public health relevance; receptor; response; virome

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.

描述（由申请人提供）：了解生物，细胞和分子水平的宿主病毒相互作用对于缓解病毒发病机理至关重要。该项目的目标是发现模型有机体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Hydra是否含有类似于人类病毒的病毒，并能够测试响应病毒存在的特异性免疫基因。 Hydra提供了一个理想的模型来测试这些宿主病毒相互作用，因为它们的简单组成，易于实验操作以及它们在没有保护性屏障的情况下对环境的暴露。此外，Hydra缺乏适应性免疫特征，不含任何运动吞噬细胞，并且仅利用粘液作为保存其上皮的手段。因此，HYDRA独特地适合研究粘膜上皮的宿主病毒先天免疫。为了确定这一点，该项目由两个特定的目的组成：1。）确定利用病毒宏基因组学的九头蛇病毒组成。 2.）在存在胞质核酸的情况下阐明氢抗病毒先天免疫反应。通过实现这两个目标，我们将鉴定出引起Hydra致病状况的病毒以及类似引起人类发病机理的病毒。然后可以在此先天免疫模型系统中测试这些病毒。此外，通过确定对病毒感染有反应的Hydra抗病毒基因，我们将通过基因敲低来操纵Hydra，以确定哪些基因对于限制病毒发病机理至关重要。 公共卫生相关性：将Hydra建立为一种抗病毒粘膜先天免疫模型有机体对人类健康很重要，这是由遗传变异物中的遗传变异体现在系统发育性的古老的先天免疫基因中，与上皮性障碍的慢性炎症性疾病有关，例如克罗恩病，例如克罗恩病，例如克罗恩病，例如克罗恩病，例如克罗恩病的植物性疾病。这些多基因疾病的特征是粘膜的慢性复发。可以在Hydra模型系统中研究此类疾病状态及其对它们的反应。

项目成果

Using viromes to predict novel immune proteins in non-model organisms.

使用病毒组预测非模型生物中的新型免疫蛋白。

• DOI: 10.1098/rspb.2016.1200
• 发表时间: 2016
• 期刊: Proceedings. Biological sciences
• 作者: Quistad,StevenD;Lim,YanWei;Silva,GenivaldoGueirosZ;Nelson,CraigE;Haas,AndreasF;Kelly,LindaWegley;Edwards,RobertA;Rohwer,ForestL
• 通讯作者: Rohwer,ForestL