Molecular phylodynamics and protein modeling of infectious salmon anemia virus (ISAV)

Abstract

BackgroundISAV is a member of the Orthomyxoviridae family that affects salmonids with disastrous results. It was first detected in 1984 in Norway and from then on it has been reported in Canada, United States, Scotland and the Faroe Islands. Recently, an outbreak was recorded in Chile with negative consequences for the local fishing industry. However, few studies have examined available data to test hypotheses associated with the phylogeographic partitioning of the infecting viral population, the population dynamics, or the evolutionary rates and demographic history of ISAV. To explore these issues, we collected relevant sequences of genes coding for both surface proteins from Chile, Canada, and Norway. We addressed questions regarding their phylogenetic relationships, evolutionary rates, and demographic history using modern phylogenetic methods.ResultsA recombination breakpoint was consistently detected in the Hemagglutinin-Esterase (he) gene at either side of the Highly Polymorphic Region (HPR), whereas no recombination breakpoints were detected in Fusion protein (f) gene. Evolutionary relationships of ISAV revealed the 2007 Chilean outbreak group as a monophyletic clade for f that has a sister relationship to the Norwegian isolates. Their tMRCA is consistent with epidemiological data and demographic history was successfully recovered showing a profound bottleneck with further population expansion. Finally, selection analyses detected ongoing diversifying selection in f and he codons associated with protease processing and the HPR region, respectively.ConclusionsOur results are consistent with the Norwegian origin hypothesis for the Chilean outbreak clade. In particular, ISAV HPR0 genotype is not the ancestor of all ISAV strains, although SK779/06 (HPR0) shares a common ancestor with the Chilean outbreak clade. Our analyses suggest that ISAV shows hallmarks typical of RNA viruses that can be exploited in epidemiological and surveillance settings. In addition, we hypothesized that genetic diversity of the HPR region is governed by recombination, probably due to template switching and that novel fusion gene proteolytic sites confer a selective advantage for the isolates that carry them. Additionally, protein modeling allowed us to relate the results of phylogenetic studies with the predicted structures. This study demonstrates that phylogenetic methods are important tools to predict future outbreaks of ISAV and other salmon pathogens.

Low virulent infectious salmon anaemia virus (ISAV-HPR0) is prevalent and geographically structured in Norwegian salmon farming

“…from virulent ISAV to ISAV-HPR0 (Kibenge et al 2009, Castro-Nallar et al 2011, rather than by deletion events (Mjaaland et al 2002, Nylund et al 2003. In the present analyses, the time period between sampling did not contribute to explain the association between ISAV-HPR0 and virulent ISAV, lending no support to either direction of hypothetical transition events.…”

Development of a Reverse Genetic System for Infectious Salmon Anemia Virus: Rescue of Recombinant Fluorescent Virus by Using Salmon Internal Transcribed Spacer Region 1 as a Novel Promoter

“…Modeling the HE protein of ISAV901_09 with GFP inserted within the HPR region. The HE sequence of ISAV 901_09 was obtained from the GenBank database (ADF36510.1) and then aligned with the aid of ClustalW (40) in the context of sequences of the crystal structure of the glycoprotein hemagglutinin-esterase-fusion (HEF) of influenza virus C (PDB entry 1FLC) (41). The PSIPRED prediction server for secondary structures was used to corroborate that the alignment had been done correctly (http://bioinf.cs.ucl.ac.uk/psipred/) (42).…”

Scientific Opinion on infectious salmon anaemia (ISA)

“…The evolutionary rate of different ISAV segments has been estimated to be about an order of magnitude lower than that of influenza A viruses (Plarre et al, 2012), but for the HE gene, the rate estimate was also lower than that obtained for a different ISAV dataset (Castro-Nallar et al, 2011). The evolutionary rate of different ISAV segments has been estimated to be about an order of magnitude lower than that of influenza A viruses (Plarre et al, 2012), but for the HE gene, the rate estimate was also lower than that obtained for a different ISAV dataset (Castro-Nallar et al, 2011).…”

“…To gain further insights into the process of virulence evolution, a quantitative assessment of the different evolutionary forces for ISA would be useful, in particular the relative contribution of mutation and reassortment processes. The evolutionary rate of different ISAV segments has been estimated to be about an order of magnitude lower than that of influenza A viruses (Plarre et al, 2012), but for the HE gene, the rate estimate was also lower than that obtained for a different ISAV dataset (Castro-Nallar et al, 2011). This implies that the tempo and mode of ISAV evolution may need further investigation.…”