Molecular basis of fish defences against viruses

鱼类防御病毒的分子基础

• 批准号: 341304-2012
• 负责人: Rise, Matthew
• 金额: $ 2.26万
• 依托单位: Memorial University of Newfoundland
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=595365
• 关键词: Molecular; basis; fish; defences; against

Viral pathogens such as nodaviruses and infectious salmon anemia virus (ISAV) are serious threats to cultured and wild fish. Much of what is currently known regarding fish gene and protein expression responses to viruses and other immune stimuli involves later life stage fish (i.e. juveniles to adults). However, little is known regarding comparative aspects of antiviral responses in fishes, how early life stage (i.e. embryonic and larval) fish defend themselves against aquatic viruses, and how environmental stressors such as heat stress influence the development and function of fish immune systems. The proposed research utilizes functional genomics tools such as DNA microarrays (also called "gene chips") and other approaches (e.g. target gene knockdown experiments) to study and compare the genes, gene products, and mechanisms involved in antiviral immune responses during different life stages of teleost fish from embryo to adult. In addition, I and my trainees will investigate the impact of heat stress on embryonic and larval fish innate immune systems and antiviral immune responses. Atlantic salmon, Atlantic cod, and zebrafish will be used as models in this research. These three species of fish are evolutionarily diverged, and are well-supported by genomic resources such as sequence databases and DNA microarrays. I hypothesize that our comparative studies of interferon pathway and other immune-relevant gene structure, expression, and function using salmon, cod, and zebrafish as models will allow identification of conserved components of fish defence (e.g. genes and molecular pathways involved in antiviral defence responses of all teleost fish), as well as lineage-specific mechanisms of defence (e.g. present in cod but not salmon). I anticipate that this research will make important contributions to the field of developmental and comparative immunology (e.g. by investigating the genes and proteins involved in embryonic and larval fish responses to viral stimuli in the presence and absence of elevated ambient temperature), and be invaluable to several research areas including evolutionary biology, fisheries, and aquaculture.

病毒性病原体，如诺达病毒和传染性鲑鱼贫血病毒（ISAV）是对养殖和野生鱼类的严重威胁。关于鱼类基因和蛋白质表达对病毒和其他免疫刺激的反应，目前已知的大部分内容涉及鱼类的后期生活阶段（即幼年到成年）。然而，关于鱼类抗病毒反应的比较方面，鱼类如何在生命早期阶段（即胚胎和幼虫）保护自己免受水生病毒的侵害，以及热应激等环境应激因素如何影响鱼类免疫系统的发育和功能，人们知之甚少。本研究利用功能基因组学工具，如DNA微阵列（也称为“基因芯片”）和其他方法（如靶基因敲低实验），研究和比较硬骨鱼从胚胎到成鱼的不同生命阶段中参与抗病毒免疫反应的基因、基因产物和机制。此外，我和我的学员将研究热应激对胚胎和幼鱼先天免疫系统和抗病毒免疫反应的影响。本研究将以大西洋鲑鱼、大西洋鳕鱼和斑马鱼为模型。这三种鱼类在进化上是不同的，并得到序列数据库和DNA微阵列等基因组资源的充分支持。我假设，我们以鲑鱼、鳕鱼和斑马鱼为模型，对干扰素途径和其他免疫相关基因结构、表达和功能的比较研究，将允许鉴定鱼类防御的保守成分（例如，所有硬骨鱼的抗病毒防御反应中涉及的基因和分子途径），以及谱系特异性防御机制（例如，存在于鳕鱼中，而不存在于鲑鱼中）。我预计这项研究将对发育和比较免疫学领域做出重要贡献（例如，通过研究在环境温度升高和不升高的情况下，胚胎和幼鱼对病毒刺激的反应所涉及的基因和蛋白质），并对包括进化生物学、渔业和水产养殖在内的几个研究领域具有不可估量的价值。