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年以来保持了8.8%的年增长率，是野生鱼类的可接受补充和替代品。水产养殖将继续在养活世界日益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，这容易导致疾病。疾病的传播是水产养殖业最令人担忧的威胁。传染性三文鱼贫血(ISA)是海水养殖大西洋鲑鱼最重要的病毒性疾病。ISA病毒(ISAV)目前在不同鲑鱼养殖区的鱼类种群中流行。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ISAV在养殖鱼中的演变对于监测和疫苗株的选择和设计很重要。此外，对鱼类抗药性机制的有限了解使缓解生物分子(疫苗和抗病毒药物)的开发具有挑战性。拟议的研究计划的长期目标是获得详细的分子理解，了解ISAV是如何在鱼类宿主中进化产生变异的HPR0病毒(即其表面包膜糖蛋白血凝素-酯酶没有缺失)及其确切的致病机制。本研究的主要目的是：(1)研究不同ISAV基因在鱼类细胞系复制过程中的遗传多样性，并探讨ISAV的基因重组和重组能力；(2)鉴定细胞特异性的抗病毒基因并阐明其作用机制；(3)开发针对ISAV的缓解生物分子(疫苗和抗病毒药物)。这些研究将促进我们对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将对水产养殖业具有重要的实际应用，而且将继续具有重大的局部病毒学兴趣，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.