Viral evolution of the fish orthomyxovirus isavirus

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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.