Viral evolution of the fish orthomyxovirus isavirus

水产养殖是世界上增长最快的食品生产部门，自1970年以来保持着8.8%的年增长率，为野生鱼类提供了可接受的补充和替代品。水产品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涉及大量的鱼类压力，这助长了疾病。疾病的传播是水产养殖最令人担忧的威胁。传染性鲑鱼贫血症（伊萨）是海洋养殖大西洋鲑鱼最重要的病毒性疾病。伊萨病毒（ISAV）现在在不同鲑鱼养殖区的鱼类种群中流行。解释ISAV的出现、毒力和持久性的遗传特征还没有得到很好的研究。了解养殖鱼类中ISAV的进化对于监测和疫苗株的选择和设计非常重要。此外，由于对鱼类耐药性机制的了解有限，开发缓解生物分子（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HPR 0病毒（所谓的表面包膜糖蛋白血凝素酯酶无缺失）及其确切发病机制的详细分子理解。本研究计划的主要目标是：（1）研究不同ISAV基因在允许的鱼类细胞系中复制过程中的遗传多样性，并研究ISAV的遗传重组和重配能力;（2）鉴定细胞特异性抗病毒基因并阐明其作用模式;（3）开发减轻ISAV的生物分子（疫苗和抗病毒药物）。这些研究将进一步加深我们对ISAV病毒-细胞和病毒-宿主相互作用的理解。这项研究的结果不仅将有重要的实际应用水产养殖业，但也将继续显着的局部病毒学的兴趣，因为ISAV是唯一已知的变温正粘病毒。

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.