Molecular basis of fish defences against viruses

诺达病毒和传染性鲑鱼贫血病毒(ISAV)等病毒病原体对养殖和野生鱼类构成严重威胁。目前已知的关于鱼对病毒和其他免疫刺激的基因和蛋白质表达反应的大部分涉及生命后期的鱼(即从幼鱼到成鱼)。然而，关于鱼类抗病毒反应的比较方面，早期生命阶段(即胚胎和幼体)鱼类如何防御水生病毒，以及热应激等环境应激源如何影响鱼类免疫系统的发育和功能，人们知之甚少。这项拟议的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(如靶基因敲除实验)来研究和比较硬骨鱼从胚胎到成鱼不同生活阶段中参与抗病毒免疫反应的基因、基因产物和机制。此外，我和我的受训者将研究热应激对胚胎和仔鱼先天免疫系统和抗病毒免疫反应的影响。大西洋鲑鱼、大西洋鳕鱼和斑马鱼将作为这项研究的模型。这三种鱼在进化上是不同的，并得到了基因组资源的良好支持，如序列数据库和DNA微阵列。我推测，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、表达和功能进行的比较研究，将有助于识别鱼类防御的保守成分(例如，参与所有硬骨鱼抗病毒防御反应的基因和分子途径)，以及特定谱系的防御机制(例如，存在于鳕鱼中，但不存在于鲑鱼中)。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，通过研究在存在和不存在环境温度升高的情况下，胚胎和仔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无价的价值。*

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. **** ****************