Review article: Salmon alphavirus (SAV 1-6) and potential

Vaccinations in Atlantic salmon (Salmo salar)

By Michelle Bua

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 into subtypes based on genetic differences in RNA sequencing, 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. This paper will review some scientific articles involving the impact of
SAV on salmon and the salmon farming community, and the possible vaccines against it.












Introduction
Pancreas disease (PD) in Atlantic salmon (Salmo salar) was first described in 1987 [1].
Since then, it has become well-known that PD affects salmon by causing 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. In southern Norway, where numerous S. salar farming sites exist, PD
outbreak reports were highest from Jan 2009 to Dec 2010 [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]. Once the subtypes were
categorized, researchers began to explore the pathological differences between them.
Pathological infliction varies between subtypes. Viral subtypes are spread via horizontal disease
transmission, which is transmission between species members not in a parent-offspring
relationship [6]. In 2011, Grahams 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 [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. Grahams experiment in 2012 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 by Graham 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 vaccination, diagnosis, and
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. This allowed researchers to provide the amount of tissue
damage based on a scaled tissue damage interval [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 of tissue damage were again observed
in the pancreas, along with lower levels in the heart, and in red and white muscles by Braceland
in 2013. 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]. Karlsen 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
The methods in Herath and Braceland provide the foundation for developing reliable
SAV detection based on the abundance of interferons, and Mx proteins [8,10]. Interferons are
proteins that are released by naturally occurring cells in the presence of a virus or pathogen.
These proteins are important for early immune response since they increase the ability of healthy
cells to resist infection, and activate killer T cells, which fight infection. Mx proteins have
antiviral activity and are induced by interferons. 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 [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
1. McVicar, A. H. (1987). Pancreas disease of farmed Atlantic salmon, Salmo salar, in
Scotland: Epidemiology and early pathology. Aquaculture, 67(1), 71-78.McVicar
2. Tavornpanich, S., Paul, M., Viljugrein, H., Abrial, D., Jimenez, D., & Brun, E. (2012). Risk
map and spatial determinants of pancreas disease in the marine phase of Norwegian Atlantic
salmon farming sites. BMC veterinary research, 8(1), 172.
3. Graham, D. A., Wilson, C., Jewhurst, H., & Rowley, H. (2008). Cultural characteristics of
salmonid alphavirusesinfluence of cell line and temperature. Journal of fish
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