infectious salmon anemia virus

Identity

Preferred Scientific Name

• infectious salmon anemia virus Hovland et al., 1994

International Common Names

• English: infectious salmon anaemia virus; infectious salmon anemia virus; salmon anaemia agent

English acronym

• ISAV

Taxonomic Tree

• Domain: Virus
•     Group: "Negative sense ssRNA viruses"
•         Group: "RNA viruses"
•             Order: Mononegavirales
•                 Family: Orthomyxoviridae
•                     Genus: Isavirus
•                         Species: infectious salmon anemia virus

Disease/s Table

Distribution Table

The distribution in this summary table is based on all the information available. When several references are cited, they may give conflicting information on the status. Further details may be available for individual references in the Distribution Table Details section which can be selected by going to Generate Report.

Pathogen Characteristics

ISAV is a pleiomorphic enveloped virus, 100-130 nm in diameter, with 10-12 nm surface projections exhibiting haemagglutination, receptor-destroying and fusion activity (Dannevig et al., 1995; Eliassen et al., 2000; Falk et al., 1997; Falk et al., 2004). Endothelial cells are the main target and the virus replicates by budding from the cell membrane (Dannevig et al., 1995; Hovland et al., 1994).

The genome consists of eight single-stranded RNA segments with negative polarity ranging in length from 1.0 to 2.4 kb and with a total size of approximately 14.3 kb (Clouthier et al., 2002; Mjaaland et al., 1997). The morphological, physiochemical and genetic properties of ISAV are consistent with those of the Orthomyxoviridae (Falk et al., 1997; Mjaaland et al., 1997; Rimstad and Mjaaland, 2002; Sandvik et al., 2000), and ISAV has recently been classified as the type species of the new genus Isavirus (ICTVdB Index of Viruses http://www.ncbi.nlm.nih.gov/ICTVdb/Ictv/index.htm) within this virus family.

The nucleotide sequences of all eight genome segments have been described (Clouthier et al., 2002; Krossøy et al., 1999; Krossøy et al., 2001; Mjaaland et al., 1997; Rimstad et al., 2001; Ritchie et al., 2002; Snow and Cunningham, 2001). The viral genome encodes at least ten proteins. Four major structural proteins have been classified, including a 68 kDa nucleoprotein (segment 3; (Aspehaug et al., 2004; Falk et al., 2004; Snow and Cunningham, 2001), a 50 kDa surface glycoprotein with putative fusion activity (segment 5; (Falk et al., 2004); Mikalsen pers. communication), a 42 kDa haemaglutinin-esterase protein (segment 6; (Rimstad et al., 2001; Falk et al., 2004; Krossøy et al., 2001), and a 22 kDa matrix protein (segment 8; (Biering et al., 2002; Falk et al., 2004). Segments 1, 2 and 4 encode the viral polymerases (PB1: (Snow et al., 2003), PB2: (Krossøy et al., 1999), PA: (Clouthier et al., 2002)). The two smallest genomic segments have two open reading frames (ORF) each. The smaller ORF1 of segment 8 encodes a major component of the virus particle most likely representing the 22 kDa matrix protein (Biering et al., 2002; Falk et al., 2004), while the larger ORF2 encodes a structural protein of about 26 kDa with RNA binding properties (own results). Furthermore, preliminary results have revealed that two mRNAs are transcribed from the ISAV genomic segment 7; one is colinear with the viral RNA and the other is spliced (Biering et al., 2002). The large ORF1 of segment 7 encodes a non-structural protein, while the protein encoded by ORF2 has yet to be characterized. Both the small ORF2 protein encoded by segment 8 and the large ORF1 protein encoded by segment 7 exerts interferon type I antagonistic properties.

There is a low amino acid identity between the ISAV proteins and those of other orthomyxoviruses (13 - 25%: (Kibenge et al., 2001b; Krossøy et al., 1999; Ritchie et al., 2002; Snow and Cunningham, 2001), and the order of the genome segments encoding the proteins in ISAV appears to differ from those of influenza viruses. For transcription and expression of ISAV proteins, 8-18 nucleotide 5'-cap structures are cleaved from cellular heteronuclear RNAs (cap-stealing), and the mRNA is polyadenylated from a signal 13-14 nucleotides downstream of the 5'-end terminus of the vRNA (Sandvik et al., 2000). The buoyant density of the complete virus particles in sucrose and cesium chloride is 1.18 g/ml (Falk et al., 1997). The virus is stable between pH 5.7-9.0 (Falk et al., 1997), and the virus has a 3-log10 reduction in titre after 4 months when maintained in sterile sea water at 4°C (Rimstad and Mjaaland, 2002). The optimum temperature for replication in susceptible fish cell lines is 10-15°C. There is no replication in SHK-1 cells at 25°C or higher, and even at 20°C the yield of virus in SHK-1 cells is only 1% of the yield at 15°C (Falk et al., 1997).

The pathogenicity of ISAV varies, observed as differences in disease development and clinical signs. In determining the virulence of the virus, the genes encoding the surface molecules are of particular importance. ISAV has two main surface glycoproteins: the haemagglutinin-esterase encoded by genomic segment 6 responsible for the receptor-binding and receptor-destroying enzyme activity (Falk et al., 2004), while the fusion activity is most likely exerted by the 50 kDa protein encoded by genomic segment 5.

The ISAV molecule with the highest variability is the haemagglutinin-esterase (HE, segment 6). The overall nucleotide and amino acid sequence variability in HE is low (94-97% as compared to the Norwegian reference strain, Glesvaer/2/90. In contrast to influenza A haemagglutinin (HA), where most of the variability is located in distal parts of the molecule, most of the variability within ISAV HE is concentrated in a region predicted to lie immediately outside the viral envelope (Devold et al., 2001; Krossøy et al., 2001; Mjaaland et al., 2002a; Rimstad et al., 2001). This region is characterized by the presence of gaps, rather than single-nucleotide substitutions (Mjaaland et al., 2002a). The variability has been suggested to be generated through differential deletions as a consequence of strong functional selection, possibly related to a recent or ongoing crossing of a species barrier (Mjaaland et al., 2002a). All the European ISAV isolates can be genotyped according to deletion patterns in this highly polymorphic region (HPR). Most viruses belonging to a given HPR group derive from outbreaks with similar disease development, and cell culture replication and cytopathic effects vary between viruses from different HPR groups (Mjaaland et al., 2002a). Whether there is a link between the variation in HPR and a virulence pattern is not known. Although most of the variability between virus isolates lies in this region, other genes are most certainly of importance for virulence, as differences in mortality were found among fish experimentally infected with virus isolates with identical HRP genotype (Mjaaland et al., 2005) One candidate gene is the segment 5 encoding for the fusion protein (A. Mikalsen, pers. comm.). However other genes, such as the IFN-antagonistic gene products from segment 7 and 8 are other candidates.

Host Animals

Vectors and Intermediate Hosts

References

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Biering E, Falk K, Hoel E, Thevarajan J, Joerink M, Nylund A, Endresen C, Krossøy B, 2002. Segment 8 encodes a structural protein of infectious salmon anaemia virus (ISAV); the co-linear transcript from segment 7 probably encodes a non-structural or minor structural protein. Diseases of Aquatic Organisms, 49:117-122.

Clouthier SC, Rector T, Brown NEC, Anderson ED, 2002. Genomic organization of infectious salmon anaemia virus. Journal of General Virology, 83(2):421-428.

Dannevig BH, Falk K, Namork E, 1995. Isolation of the causal virus of infectious salmon anaemia (ISA) in a long-term cell line from Atlantic salmon head kidney. Journal of General Virology, 76(6):1353-1359.

Devold M, Falk K, Dale OB, Krossy B, Biering E, Aspehaug V, Nilsen F, Nylund A, 2001. Strain variation, based on the hemagglutinin gene, in Norwegian ISA virus isolates collected from 1987 to 2001: indications of recombination. Diseases of Aquatic Organisms, 47(2):119-128.

Eliassen TM, Frystad MK, Dannevig BH, Jankowska M, Brech A, Falk K, Romren K, Gjen T, 2000. Initial events in infectious salmon anemia virus infection: evidence for the requirement of a low-pH step. Journal of Virology, 74(1):218-227.

Falk K, Aspehaug V, Vlasak R, Endresen C, 2004. Identification and characterization of viral structural proteins of infectious salmon anemia virus. Journal of Virology, 78:3063-3071.

Falk K, Namork E, Rimstad E, Mjaaland S, Dannevig BH, 1997. Characterization of infectious salmon anemia virus, an orthomyxo-like virus isolated from Atlantic salmon (Salmo salar L.). Journal of Virology, 71(12):9016-9023.

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Links to Websites

Distribution Maps

• = Present, no further details
• = Evidence of pathogen
• = Widespread
• = Last reported
• = Localised
• = Presence unconfirmed
• = Confined and subject to quarantine
• = See regional map for distribution within the country
• = Occasional or few reports

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