A Review of Salmon Alphavirus (SAV 1-6) and Potential Vaccinations

in Atlantic Salmon (Salmo salar)

Biological Science,
California State University Fullerton,
800 N State College Blvd,
Fullerton, CA, 92831, US



Abstract
Pancreas disease (PD) in Atlantic salmon (S. salar) has been a major factor contributing
to salmon mortality, causing considerable economic losses to European fisheries and aquaculture
businesses. The cause of PD went undiscovered when first described in 1987, since then its
been attributed to salmon alphavirus (SAV) infection. Currently, SAV has been categorized into
6 subtypes based on genetic differences in RNA sequencing. The subtypes differ in their
pathological intensities and in their geographical distributions. Upon SAV infection, S.salar
experience intense heart and pancreas tissue damage. However, increased interferon and Mx
protein load in conjunction with changes in blood serum protein abundance were associated with
a fast-acting immune responses. Vaccines based on inactivated whole SAV strains have been
developed to combat the spread of SAV and protect vital salmon stock from mortality. In this
review article, we will compare SAV subtypes 1 and 3, possible vaccinations, and their effects
on S. salar.




Introduction
Since first described in 1987, Pancreas disease (PD) has been associated with total
necrosis of exocrine pancreas, loss of feeding response and emaciation [1]. The occurrence of
PD in S. salar greatly contributes to economic losses in numerous European fishing industries
and aquaculture businesses. From January 2009 to December 2010, Southern Norway farming
S.salar had reported highest PD outbreaks [2]. The outbreak reports were also associated with
high mortality rates, interrupted reproduction cycles, and decreased growth rates [2]. Research
efforts had not pinpointed the diseases causative agent, but closer examination of the pathology
of PD may have been required to do so. Although research communities have known the
consequences of PD for some time, its origin has only recently been discovered.
The cause of PD in S. salar has been attributed to the salmon alphavirus (SAV) [3,4]. As
a result, various research communities have increased efforts to scrutinize SAV and its effects on
S. salar in order to find methods to alleviate economic losses. Increased knowledge of SAV
spurred efforts to design vaccinations based on genomic strains of SAV subtypes and test them.
In this review, we aim to determine the importance of the different SAV subtypes (1-6) and how
subtypes are differentiated. We also explore research carried out to produce viable treatments
and preventative methods. Determining the effects of SAV on S. salar and the success of
potential vaccinations may benefit salmon farming industries in the future.
SAV Subtypes
The SAV subtypes have been described and categorized by number (1-6), based on
genetic differences in their respective RNA sequences [5]. Fringuellis study utilized real time
Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR) in order to track the number of
genetic differences between subtypes. Sequencing analysis produced data on genetic differences
and the subtypes were categorized based on percent similarity [5]. Pathological differences
between subtypes were explored once the subtypes were categorized. Pathological inflictions
vary between subtypes. Grahams study found that viral subtypes are spread via horizontal
disease transmission; which is transmission between species members and not in a parent-
offspring relationship [6]. Grahams study also showed that subtypes 1 and 3 cause higher
intensities of pathological effects, including tissue damage to the heart and pancreas (Table 1).
As a result, much of the research done on the effects of SAV and SAV vaccinations have tested
SAV subtypes 1 and 3. Histology and qRT-PCR were used to determine differences in
pathological effects, however, histology was claimed to be the better method for determination
[6].


Graham et al. 2011


SAV subtypes were categorized based on their geographic distribution in Ireland and
Scotland [7]. RT-PCR data showed a mixture of subtypes across the regions studied while SAV
1 was most abundant. Graham and Fringuelli [7] did not include SAV 3 as it occurs
predominantly off the coast of Norway. SAV subtypes occur simultaneously across geographic
regions with the exception of SAV 3, which is thought to occur only in Norway. The subtypes
differ genetically and in the pathological intensity subsequent to infection. These findings are
valuable for future studies that will explore vaccinations, diagnosis, and the epidemiology of
SAV.
Effects of SAV on S. salar
Infection of SAV in S. salar is detrimental to their growth and health. Young S. salar
experimentally infected with SAV-1 experienced pathological changes to the heart and pancreas
which resulted in damaged tissue as early as three days after infection [8]. These changes were
examined via immunohistopathology, which allowed researchers to provide a score for the
amount of tissue damage, onto a tissue damage interval scaled [8]. SAV 1 infection resulted in
more tissue damage to the pancreas than the heart, which is expected since SAV is a causative
agent of PD in S. salar [8]. SAV 1 infection was also associated with a fast-acting immune
response measured via interferon load and production of Mx proteins [8]. Interestingly, salmon
mortality was not observed in this study. However, mortality rates may be associated with
season changes [9]. The connection between S. salars potential sensitivity to environmental
changes and SAV susceptibility has not been explored.
Changes in protein abundance upon infection of SAV 3 were associated with variable
pathological responses in S. salar [10]. The highest levels tissue damage were again observed in
the pancreas, along with lower levels in the heart, and in red and white muscles [10]. The
absence of recorded tissue damage in the red and white muscle may be attributed to differences
in pathological responses between SAV subtypes [8]. Upon alteration of S. salars expressed
blood serum proteins, protein abundance was associated with two phenomena: increased
pancreas and heart damage or intensified early immune responses to infection [10]. S. salar are
negatively affected by SAV in that the virus results in tissue damage and growth rate reduction.
Better understanding of the immune responses and proteome modifications S. salar undergo
post-infection will provide applicable treatments of SAV.
Vaccines
Since the association between SAV and PD was made, efforts have increased in order to
produce viable vaccinations to combat SAV transmittance. Inactivated whole virus (IWV)
vaccines were shown to provide better protection against SAV than DNA and subunit vaccines
[11]. S. salar vaccinated with IWV experienced complete protection against mortality, while
virus replication and pathological changes were inhibited in the pancreas and heart [11].
Similarly, IWVs were used to demonstrate effective protection against SAV infection and
resulting PD [12]. This study was the first to explore the efficacy of vaccinations both in
laboratory and field conditions. The consensus is that vaccinations based on inactivated SAV
strains provide the most superior protection against infection, which prevents the development of
PD.
Implications
Proteins such as interferon proteins, Mx proteins, and changes in protein abundance
possess the ability for acting as biomarkers to detect SAV infection [1,6]. The examination of
early immune responses by measuring changes in protein levels (interferon proteins or Mx
proteins) may also be developed to utilize an artificial selection regime. The regime would
consist of selecting individuals that possess the highest interferon and Mx protein production
levels [8]. Those individuals could then be bred to pass on genetic advantages and so forth.
Prior research would be necessary to develop safe and ethical methods for carrying out artificial
selection of S. salar. SAV has been described in detail and research communities continue to
seek out solutions to deter its spread and its effects on S. salar populations. Safe and effective
vaccinations based on inactive SAV strains provide the best, most available option for inhibiting
viral replication and protection from mortality caused by PD.
References
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