Evolution of infectious salmon anaemia virus (ISA virus).

Infectious salmon anaemia virus, ISA virus (genus Isavirus, family Orthomyxoviridae), emerged in Norwegian salmon culture in the mid-80s. The genome consists of eight segments coding for at least 10 proteins. ISA viruses show many of similarities to influenza A viruses but differ in many important aspects such as the number of hosts, the host population structure and the route of transmission. The only known hosts and reservoirs for ISA viruses are salmonids found in countries surrounding the North Atlantic. In this study, four different segments of the genome of about 100 ISA viruses have been sequenced in an attempt to understand the evolution of ISA viruses and how these viruses are maintained in and transmitted between populations of farmed Atlantic salmon. The four gene segments code for the nucleoprotein (NP), the putative acid polymerase (PA), the fusion protein (F) and the haemagglutinin-esterase (HE). Analysis of these four genes showed that the substitution rates of the internal proteins (NP and PA) are lower than those of the two surface proteins (F and HE). All four segments are evolving at a lower rate than similar genes in influenza A viruses. The ISA virus populations consist of avirulent viruses and pathogenic strains with variable virulence in Atlantic salmon. Recombination resulting in inserts close to the proteolytic-cleavage site of the precursor F0 protein and deletions in the stalk region of the HE protein seem to be responsible for the transition from avirulent ISA viruses to pathogenic strains. It is also shown that reassortment is a frequent event among the dominating ISA viruses in farmed Atlantic salmon. The pattern that is obtained after phylogenetic analysis of the four gene segments from ISA viruses suggests that the variation is limited to a few distinct clades and that no major changes have occurred in the ISA virus population in Norway since the first viruses were isolated. Calculation of the time of most recent common ancestor (TMRCA) suggests that the Norwegian ISA viruses separated from the European subtype found in North America between 1932 and 1959. The TMRCA data also suggest that the ISA viruses in Chile were transmitted from Norway in the period from 1995 to 2007, depending on which of the four genes were used in the analysis.