Viral evolution of the fish orthomyxovirus isavirus

水产养殖是世界上增长最快的粮食生产部门，自1970年以来保持8.8%的年增长率，是野生鱼类的一种可接受的补充和替代品。水产养殖将继续在养活世界不断增长的人口方面发挥至关重要的作用。然而，鱼类养殖的集约化和密度的增加给鱼类带来了巨大的压力，从而促进了疾病的发生。疾病的传播是对水产养殖最可怕的威胁。传染性鲑鱼贫血（ISA）是海洋养殖大西洋鲑鱼最重要的病毒性疾病。ISA病毒（ISAV）现在在不同鲑鱼养殖区域的鱼类种群中流行。ISAV的出现、毒力和持久性的遗传特征尚未得到很好的研究。了解养殖鱼类中ISAV的演变对监测和疫苗株的选择和设计具有重要意义。此外，由于对鱼类耐药机制的了解有限，使得开发减轻生物分子（疫苗和抗病毒药物）具有挑战性。拟议研究计划的长期目标是获得ISAV如何在鱼类宿主中进化以产生变异HPR0病毒（其表面包膜糖蛋白血凝素酯酶没有缺失而被称为变异HPR0病毒）及其确切发病机制的详细分子理解。本课题的主要目的是：(1)研究不同ISAV基因在受纳鱼细胞系复制过程中的遗传多样性，研究ISAV基因重组和重配的能力；(2)鉴定细胞特异性抗病毒基因并阐明其作用方式；(3)开发针对ISAV的减轻性生物分子（疫苗和抗病毒药物）。所提出的研究将促进我们对ISAV病毒-细胞和病毒-宿主相互作用的进化的理解。这项研究的结果不仅对水产养殖业有重要的实际应用，而且由于ISAV是唯一已知的变温正黏液病毒，因此也将继续具有重要的局部病毒学意义。

Aquaculture is the world's fastest growing food production sector, sustaining an annual growth rate of 8.8% since 1970 and providing an acceptable supplement to and substitute for wild fish. Aquaculture will continue to be of crucial importance in feeding the world's growing human population. However, the intensification of fish farming and increased densities involves substantial fish stress which facilitates diseases. The spread of diseases is the most feared threat to aquaculture. Infectious salmon anaemia (ISA) is the most important viral disease of marine-farmed Atlantic salmon. ISA virus (ISAV) is now endemic in fish populations in the different salmon farming regions. The genetic features that account for the emergence, virulence and persistence of ISAV are not well studied. Understanding the evolution of ISAV in farmed fish is important for surveillance and vaccine strain selection and design. Moreover, the limited knowledge about the fish resistance mechanisms makes development of mitigating biological molecules (vaccines and antiviral drugs) challenging. The long-term goal of the proposed research program is to gain a detailed molecular understanding of how ISAV is evolving in the fish host to generate variant HPR0 virus (so called for having no deletion in its surface envelope glycoprotein haemagglutinin-esterase) and its precise mechanisms of pathogenesis. The main objectives of this research program are: (1) to study the genetic diversity of the different ISAV genes during replication in permissive fish cell lines, and investigate the capacity for genetic recombination and reassortment in ISAV; (2) to identify cell-specific antiviral genes and elucidate their mode of action; and (3) to develop mitigating biological molecules (vaccines and antiviral drugs) against ISAV. The proposed studies will advance our understanding of the evolution of virus-cell and virus-host interactions of ISAV. The outcomes of this research will not only have important practical applications for the aquaculture industry, but will also continue to be of significant topical virological interest since ISAV is the only known poikilothermic orthomyxovirus.