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  • Abstract The family Orthomyxoviridae is well known for containing influenza viruses with a segmented RNA genome that is prone to gene reassortment in mixed infections (known as antigenic shift) resulting in new virus subtypes that cause pandemics, and cumulative mutations (known as antigenic drift), resulting in new virus strains that cause epidemics. This family also contains infectious salmon anemia virus (ISAV) and tilapia lake virus (TiLV), which are a unique orthomyxoviruses that infect fish and is unable to replicate above room temperature (24°C). This chapter describes the comparative virology of members in the family Orthomyxoviridae in general, helping to understand the emergent teleost orthomyxoviruses, ISAV and TiLV. The most current information on virus–host interactions of the fish orthomyxoviruses, particularly ISAV, as they relate to variations in virus structure, virulence, persistence, host range and immunological aspects is presented in detail.
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