Infectious Salmon Anemia Virus (ISAV)

atlanticsalmon
http://www.fish.state.pa.us/pafish/atlantic_salmon.jpg

Contents:

History                    

The Virus

Detection of the Virus

Pathogenesis

Risk Factors

Life Cycle of the Atlantic Salmon

Vaccines

Management, Control and Treatment

Links

References


History:

Infectious Salmon Anemia virus (ISAV) is a virus of marine fish, primarily affecting salmonids, especially Atlantic salmon, Salmo salar.5   The main implications of ISAV  at this current date, is its affects on farmed Atlantic salmon.  The clinical disease  within farmed Atlantic salmon caused  by  ISAV is devastating, potentially causing huge economic losses to affected fish farms.   Atlantic salmon with clinical disease have hemorrhagic liver necrosis, pale gills, exophthalmia, ascites, renal interstial hemorrhage, leucopenia and tubular nephrosis, and subsequently high mortalities.1,5  Simply put, diseased fish exhibit lethargy, anorexia, anemia and death.8  The first identification of clinical disease from this virus was described in 1984 in Norway.2  In 1996, a disease presenting very similarly to ISAV occurred in farmed Atlantic salmon in New Brunswick, Canada.2   The initial cases were reported as haemorrhagic kidney syndrome (HKS).7  However, it was later  determined that  the HKS  outbreak  was  actually  caused by the pathogen ISAV.7  Due to the occurrence of ISAV occurring first in Norway and then Canada, it was originally hypothesized that both the North American and European viruses were one and the same.  However, in 2001, Krossy et. al, produced a study which proved that on the basis of mutation rates that the two isolates of the Norwegian and the Canadian infectious anemia viruses diverged around 1900, coinciding with the transportation of salmonids between the two geographical regions.

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The Virus:

ISA  is a virus of the family Orthomyxoviridae, genus Isavirus.5   Since ISA belongs to the viral family Orthomyxoviridae, it shares many of the physiochemical features with influenza viruses.5  The virus is an enveloped single-stranded negative sense mRNA virus 90-140nm in size, with associated HA, hemaglutinin proteins capable of agglutination red blood cells, and a HE protein, which is  an esterase  displaying receptor-destroying enzyme activity.The genome for the virus consists of eight segments, all of which have been sequenced.The genome is 14.3kb in size total, with the segments ranging is size from 1.0 to 2.4kb.5  At least 10 proteins are encoded for via the genome, nine structural and one non-structural.

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Detection of the Virus:

Besides correlation with clinical signs, laboratory techniques are also available for diagnosis.  Tests include histological examination , electron microscopy, virus isolation using cell line SHK-1 and/or CHSE-214 cell lines,  use of RT-PCR, and IFAT on positive virus isolates or on tissue samples from suspected fish, in situ hybridization on tissue samples from suspected fish, ELISA and an indirect competitive ELISA (detecting ISAV-specific antibodies).5

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Pathogenesis:

Transmission of ISAV does not required direct contact and can be passed from infected individuals to non-infected individuals via contaminated water (i.e. horizontal transmission). ISAV can also be passed along via blood, infected tissues, and feces.8  It has also been demonstrated within laboratory settings that sea lice, an external parasite of salmonids, are capable of acting as mechanical transmitters of ISAV.8

First signs of disease are subtle, such as darkening of skin colour.  Two days post skin darkening, individuals begin to show decreased swimming ability.  Shortly after reduced swimming ability, fish become moribund and die.  Pathological results show ascites, exophthalmia with associated hemorrhage, hemorrhagic liver necrosis, pale gills, renal interstial hemorrhage, leucopenia, petechiae in the viscera and tubular nephrosis.1,5,10  Death occurs normally within days to weeks, probably dependent upon the virulence of the ISAV strain.1,5,10

Virulence of the various strains of ISAV range from low to high.  Low virulence strains are designated as <50% mortality, high virulence strains as >90% and mid in between.  High virulence strains are also capable of causing low mortality in rainbow trout (Oncorhynchus mykiss), but with a longer disease course.4

Viral pathogenesis within the host is not fully described as of yet, however, belonging to the viral family Orthomyxoviridae, replication of the virus would closely resemble that of other influenza viruses.5  The HA protein is important in attachment.  However, HA is not cleaved in ISAV as with other influenza viruses.5  Once bound to the host cell, ISAV is internalized into the endosomes and low-pH-dependent fusion of the viral envelope with the endosomal membrane occurs.5   The HA protein of ISA does not demonstrate the high level of variation as with other influenza viruses, having only two variants in comparison with sixteen.  The variation of HA of the ISAV isolates correlates with the genetic variation between the North American and European types.5,6  Even though ISA has HA, virus replication occurs in leucocytes and endothelial cells lining the heart and blood vessels1,5,9,10   

ISAV may be found in many other fish species, including salmonids and non-salmonids: sea trout (Salmo trutta trutta), brown trout (Salmo trutta fario and lacustra), rainbow trout, eels (Anguilla rostrata), herring (Clupea harengus), alewife (Alosa pseudoharengus), arctic char (Salvelinus alpinus), mackerel (Scomber scombrus), Atlantic cod (Gadu morhua), haddock (Melanogrammus aeglefinus), Atlantic halibut (Hippoglossus hippoglossus), pollock (Pollachius virens), American shad (Alosa sapidissima), winter flounder (Pseudopleuronectes americanus).5  Most species besides Atlantic salmon when infected are asymptomatic.5  Susceptibility of Atlantic salmon to ISAV may be related to genetics, specifically MHC classes I and II polymorphisms.1   Pollock and cod collected from ISAV infected nets of salmon farms are capable of infection with ISAV, but are able to clear the virus within a week of infection.  Studies have also been conducted to determine the infectiousness of ISAV to Pacific salmon species.5  Chum (Oncorhynchus keta), steelhead (O. mykiss, ocean run rainbow trout), chinook (O. tshawytscha) and coho (O. kisutch) were resistant to experimental infection, even at doses of 108 TCID50/ml that induces 98% in Atlantic salmon.5  Of all the species above only rainbow trout were susceptible to disease, and only from exposure to high virulence strains.4,5  Concerns with the above mentioned species being capable of infection without clinical signs is as a reservoir and source for further infection to farmed Atlantic salmon. 

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Risk Factors:

Due to the ability of the virus to be transmitted through water, sea lice, affected tissues, blood or feces, risk factors are various.1,3,8  Some risk factors for ISA viral disease are closely associated with horizontal transmission through water.  Factors such as feed boats transporting feed to various fish farm sites may transfer ISAV via such things as ballast water.8  Increased risk of transfer does occur with use of boats transferring fish directly from site to site.8  Also, studies have shown that naive sites withing 500m or an ISAV affected site have increased odds of ISA disease occurring.8   

The most significant risk factor associated with ISAV is related to the life cycle of salmonids.1   The process of  smoltification, in which young salmon transition from a freshwater environment to adapting to a saltwater environment, is a hugely physiologically demanding transformation.  During smoltification, levels of total serum proteins and total serum IgM decrease.1  Also, plasma lysozymal activities and blood leucoyte levels decrease.1   Finally, cortisol levels, a stress hormone that has negative effects on immune response, also increase during the smoltification process.1  All of these physiological and immunological changes during smoltification may significantly reduce immunocompetence, thus implicating the smoltification process as the most significant risk factor for susceptibility to ISAV.1   

As for susceptibility in farmed Atlantic salmon in comparison with wild stocks, the jury is still out.  One study produced results in which farmed stocks were more susceptible, and in another, no difference was noted, except for the process of smoltification.1  However, with regards to farmed Atlantic salmon, stress may be higher due to stocking densities and lack of ability to move (normal behaviour during large migrations through an oceanic environment).  With increased stress, one would also expect higher cortisol levels and other negative aspects, thus further immunocompromissing farmed stocks.  Also, one must remember the studies of genetic differences in MHC I and MHC II polymorphisms between farmed and wild stocks.1

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Life Cycle of the Atlantic Salmon:

Life Cycle
                                                        http://www.asf.ca/Overall/lifecycle.html

Summary of Atlantic Salmon Life Cycle:14

eggs:  deposited by adults into home streams/river gravel beds in fall, hatch in following spring
alevin:  1st stage of hatched individual, remains in gravel beds surviving off of yolk sack, 1-2cm in length
fry:  emergence from gravel beds, begin feeding, grow tho 5-8cm
parr:  parr marks appear (vertical markings on body),  remain in river for 2 to 8 years
smolt:  during spring, at a length of 12-24cm, salmon undergo physiological changes for adaptation from living in fresh water to salt water, colour change from dark with parr markings to silver without horizontal bar parr marks
adult:  undergo large migrations in the ocean, actively hunt and consume other fish species and crustaceans, in the fall, return to streams and rivers to spawn (females lay eggs in beds in the gravel known as reds, males deposit sperm, bury and cover eggs)

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Vaccines:

Within Canada, there is currently only one licensed vaccine for ISAV.  It is a killed vaccine with the trade name Forte VI.  Forte VI also contains Aeromonas salmonicida, Vibrio anguillgrum, Salmonicida ordalii bacterins.  The VBS # is 870V2X/125.0/A8.  It was licensed on 09/17/2001 by Novartis Animal Health Canada Inc, the Aqua Health Business Unit.  Novartis Canada also produces another ISAV vaccine, also a killed virus vaccine, trade name Pentium Forte ILA.  However, Pentium Forte ILA is licensed for 'Export Use Only".11

Vaccines are delivered via intra peritoneal or intramuscular route, requiring vaccination of all individuals, a daunting task considering the high number to be vaccinated and their small size (<24 cm).  Kibenge et al (2004) stated that a better vector for gene delivery of an ISA vaccine to fish organs (gills, skin, and/or gut) as first-feeding fry  could  be useful in  protecting  early stage  salmon, such as parr, before the smoltification process.5

On February 27, 2007, a US patent was granted to a DNA vaccine for ISAV.12  The DNA vaccine induces an immune response similar to that induced via natural infection and provides a better protection versus that induced via the killed virus vaccines currently available.12  Thus, the DNA vaccine may be a better option for vaccination available in the future.

Within the European Union, the location of the first documented cases of ISAV disease, vaccination of aquaculture stocks is not readily permitted.  Policy for controlling ISAV outbreaks consist of other measures, as to be discussed in 'Management, Control and Treatment'.  Vaccination may be authorized according to national contingency plans, but only to protect stocks in non-affected cages on an infected farm or to protect stocked farms adjacent to the affected area, also known as ring vaccination.13

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Management, Control, Treatment:

Due to the fast disease course of ISAV infections progressing rapidly to death, treatment consists of control measures and management.

Management techniques within the European Union consist of eradication of the confirmed population, surveillance, containment and fallowing of the affected farm sites.10,13

Within North America, vaccination is allowed.  However,  measures such as restriction of the movement of fish and eggs from ISA positive areas, sanitation, surveillance, containment, disinfection, fallowing, and sometimes eradication of the diseased population are also implemented.10

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Links:

World Organization for Animal Health.  Manual of Diagnostic Tests for Aquatic Animals 2006.
    http://www.oie.int/eng/Normes/fmanual/A_00026.htm

Canadian Food Inspections Agency.  Aquatic Animal Health Division, National Aquatic Animal Health Program.
   http://active.inspection.gc.ca/eng/searec/searece.asp

Fisheries and Oceans Canada.  National Aquatic Animal Health Registry
    http://www.dfo-mpo.gc.ca/science/aquaculture/aah_e.htm

New Brunswick Salmon Growers Association
    http://www.nbsga.com

New Brunswick Department of Agriculture and Aquaculture.
    http://www.gnb.ca/0027

Atlantic Salmon Federation.
    http://www.asf.ca/default.htm

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References:

1Glover, K.A., C. Skar, K.E. Christie, J. Glette, H. Rudra & O. Skaala (2006).  Size-dependent susceptibility to infectious salmon anemia virus (ISAV) in Atlantic salmon (Salmo salar L.) of farm, hybrid and wild parentage.  Aquaculture 254 (1-4): 82-91.

2Hammel, K.L. & I.R. Dohoo (2005).  Mortality patterns in infectious salmon anemia virus outbreaks in New Brunswick, Canada.  Journal of Fish Diseases.  28: 639-650.

3Jones, S.R.M, & D.B. Groman (2001).  Cohabitation transmission of infectious salmon anemia virus among fresh-water reared Atlantic salmon.  Journal of Aquatic Animal Health 13(4): 340-346.

4Kibenge, F.S.B., M.J.T. Kibenge, D. Groman & S. McGeachy (2006).  In vivo correlates of infectious salmon anemia virus pathogenesis in fish.  Journal of General Virology 87(9): 2645-2652.

5Kibenge, F.S.B, K. Muni, M.J.T. Kibenge, T. Joseph & E. Moneke (2004).  Infectious salmon anemia virus:  causative agent, pathogenesis and immunity.  Animal Health Research Reviews 5(1): 65-78

6Krossoy, B., F. Nilsen, K. Falk, C. Endresen, & A. Nylund (2001).  Phylogenetic analysis of infectious salmon anemia virus isolates from Norway, Canada and Scotland.  Diseases of Aquatic Organisms 44(1):  1-6

7Lovely, J.E., B.H. Dannevig, K. Falk, L. Hutchin, A.M. MacKinnon, K.J. Melville, E. Rimstad, & S.G. Griffiths (1999).  First identification of infectious salmon anemia virus in North America with haemorrhagic kidney syndrome.  Diseases of Aquatic Organisms 35(2): 145-148.

8McClure, C.A., K.L. Hammell  & I.R. Dohoo (2005).  Risk factors for outbreaks of infectious salmon anemia in farmed Atlantic salmon, Salmon salar.  Preventive Veterinary Medicine 72(3-4): 263-280.

9Moneke, E., B.O. Ikede & F.S.B. Kebenge (2005).  Viremia during infectious salmon anemia virus infection of Atlantic salmon is associated with replicating virus in leucocytes.  Diseases of Aquatic Organisms 66(2): 153-157.

10Rolland, J.B. & J.R. Winton (2003).  Relative resistance of Pacific salmon to infectious salmon anemia virus.  Journal of Fish Diseases 26: 511-520.

11 CFIA.  available:  http://active.inspection.gc.ca/eng/searec/searece.asp

12 US Patent 7183404.  Title:  Vaccine against ISA virus.  Source:  BIOSIS Previews

13Anon.  2005.  Final Report of the Aquaculture Health Joint Working Group-Subgroup on Disease Risks and Interactions Between Farmed Salmonids and Emerging Marine Aquaculture Species.  54p.  Publisher:  Fisheries Research Services.  ISBN: 0-9546490-8-7. 
    available:  http://www.marlab.ac.uk/Uploads/Documents/Final%20interactions%20report.pdf

14Atlantic Salmon Federation.  available:  http://www.asf.ca/default.htm

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Author:  Nicole D. Jamieson, April 2007