Teresa C. Michelle B., Evan R.

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 since it was first described in 1987, but has
recently been attributed to salmon alphavirus (SAV) infection. Currently, SAV has been
categorized based on genetic differences in RNA sequencing into subtypes, numbered 1-6. The
subtypes differ in their pathological intensities and in their geographical distributions. S. salar
experience intense tissue damage in the pancreas and heart upon SAV infection. 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.





Teresa C. Michelle B., Evan R.

Introduction
Pancreas disease (PD) in Atlantic salmon (Salmo salar) was first described in 1987 [8].
Since then, it has become well-known that PD affects salmon by causing total necrosis of
exocrine pancreas, loss of feeding response, and emaciation [8]. The occurrence of PD in S.
salar greatly contributes to economic losses in numerous European fishing industries and
aquaculture businesses. In southern Norway, where numerous S. salar farming sites exist, PD
outbreak reports were highest from Jan 2009 to Dec 2010 [10]. The outbreak reports were also
associated with high mortality rates, interrupted reproduction cycles, and decreased growth rates
[10]. 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) [3,11].
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 [2]. This study utilized real time Reverse
Transcriptase Polymerase Chain Reaction (qRT-PCR) in order to track the number of genetic

Teresa C. Michelle B., Evan R.

differences between subtypes. Sequencing analysis produced data on genetic differences and the
subtypes were categorized based on percent similarity [2]. Pathological differences between
subtypes were explored once the subtypes were categorized. Pathological infliction varies
between subtypes and viral subtypes are spread via horizontal disease transmission (transmission
between species members not in a parent-offspring relationship) [4]. This study 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 [4].


Graham et al. 2011


SAV subtypes were categorized based on their geographic distribution in Ireland and
Scotland [5]. RT-PCR data showed a mixture of subtypes across the regions studied while SAV
1 was most abundant. The experiment 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

Teresa C. Michelle B., Evan R.

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 [6]. These changes were
examined via immunohistopathology, which allowed researchers to provide the amount of tissue
damage a score based on a tissue damage interval scaled [6]. 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 [6]. SAV 1 infection was also associated with a fast-acting immune response
measured via interferon load and production of Mx proteins [6]. 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 [1]. The highest levels tissue damage were again observed in
the pancreas, along with lower levels in the heart, and in red and white muscles. The absence of
recorded tissue damage in the red and white muscle may be attributed to differences in
pathological responses between SAV subtypes [6]. 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 [1]. S. salar are negatively
affected by SAV in that the virus results in tissue damage and growth rate reduction. Better

Teresa C. Michelle B., Evan R.

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
[12]. S. salar vaccinated with IWV experienced complete protection against mortality, while
virus replication and pathological changes were inhibited in the pancreas and heart [12].
Similarly, IWVs were used to demonstrate effective protection against SAV infection and
resulting PD [7]. 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
Interferon, Mx protein, and changes in protein abundance possess the qualities of acting
as biomarkers to detect SAV infection [1,6]. The methods in these studies provide the basis for
developing reliable SAV detection. The examination of early immune responses 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 [6]. 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

Teresa C. Michelle B., Evan R.

inactive SAV strains provide the best, most available option for inhibiting viral replication and
protection from mortality caused by PD.






















Teresa C. Michelle B., Evan R.

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