Piscine Orthoreovirus (PRV) and Heart and Skeletal Muscle Inflammation (HSMI)

Preface

Fisheries and Oceans Canada (DFO) has received a number of inquiries regarding the presence of PRV (also known as Piscine Reovirus) and HSMI on the Pacific Coast.

The Government of Canada has an internationally recognized National Aquatic Animal Health Program (NAAHP) that is co-delivered by the Canadian Food Inspection Agency (CFIA) and DFO under the authority of CFIA’s Health of Animals Act and Health of Animals Regulations. Under NAAHP, DFO’s laboratory system provides the diagnostic testing, research and scientific advice regarding reportable pathogens of finfish, molluscs, and crustaceans.

In addition to the NAAHP, DFO’s Pacific Aquaculture Management Division has a role in fish health management through its audit program that conducts fish health audits at up to 30 active farm sites per calendar quarter. As the primary regulator for aquaculture in BC, DFO works closely with the CFIA, the aquaculture industry and other partners to identify and manage potential risks to the health of wild and farmed salmon.

DFO also engages in research associated with other microbes that may impact salmonids but are not listed in acts and regulations. As a science-based department, DFO draws on existing scientific knowledge, conducts its own research and collaborates with others. Some of this research is being conducted under the Program for Aquaculture Regulatory Research (PARR), a DFO program that supports research on aquatic animal diseases. Additionally, the Strategic Salmon Health Initiative (SSHI), co-funded by DFO, Pacific Salmon Foundation and Genome BC, is an international consortium of scientists conducting research on microbes potentially impacting BC’s wild, enhanced and farmed salmon. Both the PARR and the SSHI are also providing scientific data and information pertinent to PRV and HSMI in BC salmon.

PRV

Distribution and susceptible species

PRV is known to be present in Norway, the United Kingdom, Ireland, Chile, the United States and Canada (Biering and Garseth 2012; Kibenge et al. 2013; Siah et al. 2015). In Canada, PRV was first detected in 2011 on the west coast through RT-PCR tests from farmed Chinook salmon (Oncorhynchus tshawytscha) (K.M. Miller, pers. comm.). Since that time, additional survey work through various labs and agencies in Canada and the United States has expanded the known host range of PRV in the North Pacific Ocean to include: wild Cutthroat Trout (Oncorhynchus clarkii), wild Chinook Salmon, wild Sockeye Salmon (Oncorhynchus nerka), wild Steelhead Trout (Oncorhynchus mykiss), wild Coho Salmon (Oncorhynchus kisutch), wild Chum Salmon (Oncorhynchus keta) and farmed Atlantic Salmon (Salmo salar) (DFO 2015). These species have all tested positive for PRV through molecular testing. Detections have been made from both farmed and wild fish populations which have extended from the state of Washington north through BC to Alaska (DFO 2015; Marty et al. 2015; Siah et al. 2015).

PRV has been found in a variety of species of salmonid and non-salmonid fish. In North Atlantic waters these include farmed and wild Atlantic Salmon (Salmo salar), wild Sea-Trout (Salmo trutta), wild Great Silver Smelt (Argentina silus), wild Atlantic Horse Mackerel (Trachurus trachurus), wild Atlantic Herring (Clupea harengus) and wild Capelin (Mallotus villosus) (Wiik-Nielson et al. 2012; Garseth et al. 2013).

Genomic variability

Genomic sequencing of PRV from BC has revealed some genetic differences when compared to PRV from other regions (Kibenge et al. 2013). Based on an analysis of these genetic differences, these authors proposed that PRV first arrived in BC from Norway sometime around 2007. However, recent testing of archived samples held by DFO has revealed that PRV has been present in salmonids on the Pacific coast of North America for a much longer time than reported in that paper (Marty et al. 2015; Siah et al. 2015).

Infectivity

There is a large body of literature that has established the infectivity of PRV in Norway and its co-occurrence with the disease HSMI. More recently, DFO scientists have been investigating the infectivity and disease-causing potential of the strain of PRV present in BC. Their studies have demonstrated that PRV from BC can infect Sockeye, Chinook, and Atlantic Salmon.

After infection, PRV can reach high levels in the blood and is capable of being present for many months; these findings are similar to those from Norwegian challenge studies. However, unlike in Norway, as yet, all experimental exposures of the BC strain of PRV to Pacific and Atlantic salmon in BC have failed to induce disease or mortality. This suggests PRV in BC has a low ability to cause disease (low virulence) for these species (Garver et al. 2016a; Garver et al. 2016b).

In a collaborative study led by researchers at the DFO Pacific Biological Station, it was revealed that sockeye salmon infected with PRV exhibit a remarkable lack of response to the virus at 2 and 3 weeks after infection even though substantial viral amplification occurred during this period (Polinski et al. 2016). In contrast, when sockeye salmon were infected with infectious hematopoietic necrosis virus (IHNV), a highly pathogenic rhabdovirus enzootic to the west coast of North America, substantial changes in host immune pathways were observed including antiviral and inflammatory responses. Moreover, when sockeye salmon infected with PRV were subsequently exposed to IHNV, the PRV infection had no significant effect on the sockeye’s response to the superinfecting IHNV. Consequently, concurrent infections of PRV and IHNV do not appear to significantly influence the infectivity or severity of IHNV-associated disease in sockeye although timing of virus exposures may prove to be an important factor for determining inter-viral relationships (Polinski et al. 2016).

HSMI

The disease HSMI was first reported in farmed Atlantic Salmon in Norway in 1999 (Kongtorp et al. 2004a) resulting in farm production losses. Since then, the number of cases in Norway has steadily increased to a peak of 181 farm outbreaks reported in 2014. HSMI continues to cause reduced survival of farmed fish in Norway (Marine Harvest 2015). The disease has also been reported in farmed Atlantic Salmon in Scotland (Ferguson et al. 2005) and Chile (Godoy et al. 2016).

HSMI is characterized by mortality that ranges from negligible up to 20%, and morbidity (defined as the percentage of fish with indications of disease) that can be as high as 100% within affected populations (Kongtorp et al. 2004a). HSMI often occurs 5 to 9 months after transfer to seawater, occasionally in freshwater, and can last for several months (Kongtorp at el., 2009; Johansen at el., 2016).

In addition to morbidity, clinical signs may include accumulation of fluids in the body cavity (ascites), pale heart and liver, enlarged spleen and diffused, pinpoint hemorrhages in the internal organs (visceral petechiae). However, fish with HSMI do not necessarily all have the same clinical signs and during the early stages of the disease fish can appear healthy despite the presence of internal lesions.

Although field observations have suggested that surviving fish in affected sea cages may recover (unpublished field observations; Kongtorp et al., 2004a), non-lethal outbreaks are still considered a significant problem in Norwegian Atlantic salmon farming due to poor growth and general performance of fish following infection.

The disease HSMI is diagnosed by the occurrence of histopathologic lesions in the heart and skeletal muscle; moderate to severe panmyocarditis (inflammation in the compact and spongy layers of the myocardium); and myocardial degeneration and necrosis (Biering and Garseth 2012). The skeletal muscle also shows moderate to severe myodegeneration and necrosis of the red muscle fibres, as well as inflammation (Kongtorp et al. 2004a). Lesions in the skeletal muscle tend to occur mostly during the peak of the outbreak and, to a lesser extent, in the recovery phase (Kongtorp et al. 2006). Histopathological lesions in other organs include liver necrosis and congestion / hemorrhages in liver, kidney, spleen and gills (Kongtorp et al. 2004a).

In Norway, the diagnosis of HSMI often occurs after fish have experienced a stressful event (Lovoll et al. 2012), as is true of many diseases. Injection of Norwegian Atlantic Salmon with tissue homogenates from fish diagnosed with HSMI has, across multiple studies (Kongtorp et al. 2004a; Watanabe et al. 2006; Alne et al. 2009; Kongtorp and Taksdal 2009; Yousaf et al. 2014, Saddique 2014; Johansen et al. 2015; Johansen et al. 2016), resulted in the formation of heart and skeletal muscle lesions diagnostic of HSMI.

Association between PRV and HSMI

To date the disease HSMI always occurs in the presence of PRV. While there have been other agents in addition to PRV which have been found in fish with HSMI disease, researchers agree that PRV is one of the leading candidates to be a causative agent. PRV was first identified through sequencing of heart tissue obtained from Atlantic Salmon (Salmo salar) farmed in Norway that displayed signs of HSMI and Cardiomyopathy Syndrome (Lovoll et al. 2010; Palacios et al. 2010). Since this discovery, PRV has consistently been observed concurrently with HSMI outbreaks on farms in Norway (Lovoll et al. 2012; Wiik-Nielsen et al. 2016), and recently in Chile (Godoy et al. 2016), and HSMI has never been reproduced in the laboratory without the presence of PRV (Finstad et al. 2012; Mikalsen et al. 2012; Finstad et al. 2014).

Recently, PRV-like sequences were also found concurrently with three diseases in farmed salmonids: in Rainbow Trout in Norway, the disease grossly described as circulatory failure with haemorrhages and anaemia pathologically included liver necrosis and HSMI lesions (Olsen et al. 2015); in Coho Salmon in Chile, the disease grossly described as jaundice and anemia pathologically includes liver necrosis and HSMI-like lesions (Godoy et al. 2016) and; in farmed Coho Salmon in Japan with a condition noted as erythrocytic inclusion body syndrome (Takano et al. 2016).

While it is common for fish with HSMI to carry higher loads of PRV than disease-free fish in Norway (Palacios et al. 2010; Finstad et al. 2012; Lovoll et al. 2012), a high prevalence and load of PRV has also been seen in apparently healthy fish with no or only low-level myocarditis lesions (Lovoll et al. 2010; Palacios et al. 2010; Garseth et al. 2013). Further, although HSMI has been repeatedly transmitted to naïve fish in Norway via injection of PRV-infected material obtained from fish with HSMI (Finstad et al. 2012; Mikalsen et al. 2012; Finstad et al. 2014), similar transmission studies on the BC variant of PRV conducted at DFO have failed to generate disease in Atlantic, sockeye, or chinook salmon (Garver et al. 2016a; Garver et al. 2016b). This supports the view that factors in addition to PRV may be required for the development of HSMI.

DFO scientists, along with provincial and international colleagues, are conducting investigations to better understand the biology of PRV and HSMI in wild and farmed salmon on the west coast of North America. Examples include studies assessing the association between PRV infections and spawning success of sockeye salmon in the Fraser River (Miller et al. 2014), the potential association of PRV with disease in Pacific salmon, and the assessment of infectious agents and histological evidence of disease in farmed, wild, and enhancement salmon. Studies are also investigating whether infection with PRV in the absence of HSMI would affect how a fish may respond when exposed to other naturally occurring viruses.

A study documenting the first farm-level diagnosis of HSMI in BC was recently published (Di Cicco et al. 2017). The study showed inflammatory lesions in heart and skeletal muscle tissue diagnostic of this disease in a longitudinal study from one Atlantic Salmon farm in BC. At an individual level, not all fish carried both heart and skeletal lesions at any given point in time, but at the farm level, both were present and diagnostic of the disease.

Mild clinical signs were observed along with other gross changes in the heart, liver and spleen consistent with heart failure and no associated elevation in mortalities reported at the farm level. While this study was not designed to prove or disprove a cause and effect relationship between PRV and HSMI, PRV was found to be correlated with the development of lesions diagnostic of HSMI and spatially located within the affected tissue, consistent with HSMI etiology from other countries.

The finding of inflammatory (myocarditis) heart lesions in this study is consistent with heart lesions of suspected viral origin that have been reported through the DFO audit program since 2008, and from industry fish possibly as early as 2002, but never diagnosed to a specific disease.

This webpage will be updated with the results of significant new studies once they are available.


References

  • Alne H, Thomassen MS, Takle H, Terjesen BF, Grammes F, Oehme M, Refstie S, Sigholt T, Berge RK, Rorvik KA. 2009. Increased survival by feeding tetradecylthioacetic acid during a natural outbreak of Heart and Skeletal Muscle Inflammation in S0 Atlantic Salmon, Salmo salar L. Journal of Fish Diseases 32: 953–961.
  • Biering E, Garseth AH. 2012. Heart and Skeletal Muscle Inflammation (HSMI) of farmed Atlantic Salmon (Salmo salar L.) and the associated Piscine Reovirus (PRV). In: Feist S, editor. ICES Identification Leaflets for Diseases and Parasites of Fish and Shellfish. Copenhagen: International Council for the Exploration of the Sea; p. 6.
  • DFO. 2015. Assessment of the Occurrence, Distribution and Potential Impacts of Piscine Reovirus on the West Coast of North America. DFO Can. Sci. Advis. Sec. Sci. Resp. 2015/037.
  • DFO. 2016. Potential Diagnosis of Heart and Skeletal Muscle Inflammation in Atlantic salmon at a B.C. Fish Farm. http://news.gc.ca/web/article-en.do?nid=1069579.
  • Di Cicco E, Ferguson HW, Schulze AD, Kaukinen KH, Li S, Vanderstichel R, Wessel Ø, Rimstad, E, Gardner IA, Hammell KL, Miller KM. 2017. Heart and skeletal muscle inflammation (HSMI) disease diagnosed on a British Columbia salmon farm through a longitudinal farm study. PLOS One: http://dx.doi.org/10.1371/journal.pone.0171471
  • Finstad OW, Falk K, Lovoll M, Evensen O, Rimstad R. 2012. Immunohistochemical detection of Piscine Reovirus (PRV) in hearts of Atlantic Salmon coincides with the course of Heart and Skeletal Muscle Inflammation (HSMI). Veterinary Research 43:27.
  • Finstad OW, Dahle MK, Lindholm TH, Nyman IB, Lovoll M, Wallace C, Olsen CM, Storset AK, Rimstad E. 2014. Piscine orthoreovirus (PRV) infects Atlantic salmon erythrocytes. Veterinary Research 45(35):1297–9716.
  • Ferguson HW, Kongtorp RT, Taksdal T, Graham D, Falk K. 2005. An outbreak of disease resembling Heart and Skeletal Muscle Inflammation in Scottish farmed salmon, Salmo salar L., with observations on myocardial regeneration. Journal of Fish Diseases 28:119–123.
  • Finstad ØW. 2014. Pathogenesis of Piscine orthoreovirus (PRV) infection in Atlantic Salmon (Salmo salar). Philosophiae Doctor (PhD) Thesis 2014:28. Norwegian University of Life Science; 2014.Salmon erythrocytes. Veterinary Research 45: 35.
  • Garseth AH, Fritsvold C, Opheim M, Skjerve E Biering E. 2013. Piscine Reovirus (PRV) in wild Atlantic Salmon, Salmo salar L., and Sea-Trout, Salmo trutta L., in Norway. Journal of Fish Diseases 36:483–493.
  • Garver KA, Marty GD, Cockburn SN, Richard J, Hawley LM, Müller A, et al. 2016a. Piscine reovirus, but not jaundice syndrome, was transmissible to Chinook Salmon, Oncorhynchus tshawytscha (Walbaum), Sockeye Salmon, Oncorhynchus nerka (Walbaum), and Atlantic Salmon, Salmo salar L. Journal of Fish Diseases 39:117–128.
  • Garver KA, Johnson SC, Polinski MP, Bradshaw JC, Marty GD, Snyman HN, et al. 2016b. Piscine Orthoreovirus from Western North America is transmissible to Atlantic Salmon and Sockeye Salmon but fails to cause Heart and Skeletal Muscle Inflammation. PLoS ONE 11(1):e0146229. DOIoi:10.1371/journal.pone.0146229.
  • Godoy MG, Kibenge MJT, Wang Y, Suarez R, Leiva C, Vallejos F and Kibenge FSB. 2016. First description of clinical presentation of piscine orthoreovirus (PRV) infections in salmonid aquaculture in Chile and identification of a second genotype (Genotype II) of PRV. Virology Journal 13:98. doi:10.1186/s12985-016-0554-y.
  • Johansen LH, Thim HL, Jorgensen SM, Afanasyev S, Strandskog G, Taksda T, Fremmerlid K, McLoughlin M, Jorgensen JB, Krasnov A. 2015. Comparison of transcriptomic responses to pancreas disease (PD) and heart and skeletal muscle inflammation (HSMI) in heart of Atlantic Salmon (Salmo salar L.). Fish Shellfish Immunol. 46:612–623.
  • Johansen LH, Dahle MK, Wessel Ø, Timmerhaus G, Løvoll M, Røsæg M, Jørgensen SM, Rimstad E, Krasnov A. 2016. Differences in gene expression in Atlantic Salmon parr and smolt after challenge with Piscine orthoreovirus (PRV). Molecular Immunology 73:138–150.
  • Kibenge MJT, Iwamoto T, Wang Y, Morton A, Godoy MG, Kibenge F. 2013. Whole-genome analysis of Piscine Reovirus (PRV) shows PRV represents a new genus in Family Reoviridae and its genome segment S1 sequences group it into two separate sub-genotypes. Virology Journal 10:230.
  • Kongtorp R-T, Kjerstad A, Taksdal T, Guttvik A, Falk K. 2004. Heart and Skeletal Muscle Inflammation in Atlantic salmon, Salmo salar L: a new infectious disease. Journal of Fish Diseases 27: 351–8. doi:10.1111/j.1365-2761.2004.00549.x.
  • Kongtorp RT, Halse M, Taksdal T, Falk K. 2006. Longitudinal study of a natural outbreak of heart and skeletal muscle inflammation in Atlantic Salmon, Salmo salar L. Journal of Fish Dieases 29: 233–244.
  • Kongtorp RT, Taksdal T. 2009. Studies with experimental transmission of Heart and Skeletal Muscle inflammation in Atlantic Salmon, Salmo salar L. Journal of Fish Diseases 32:253–262.
  • Løvoll M, Wiik-Nelson J, Grove S, Wiik-Nelson C, Kristoffersen AB, Faller R, Poppe T, Jung J, Pedamallu CS, Nederbragt AJ, Meyerson M, Rimstad E, Tengs T. 2010. A novel Totivirus and Piscine Reovirus (PRV) in Atlantic Salmon (Salmo salar) with Cardiomyopathy Syndrome (CMS). Virology Journal 7:309.
  • Løvoll M, Allercon M, Jensen BB, Taksdal AB, Kristoffersen AB, Tengs T. 2012. Quantification of Piscine Reovirus (PRV) at different stages of Atlantic salmon Salmo salar production. Diseases of Aquatic Organisms 99:7–12.
  • Marine Harvest annual report 2015. http://www.marineharvest.com/investor/annual-reports/
  • Marty GD, Morrison DB, Bidulka J, Joseph T, Siah A. 2015. Piscine reovirus in wild and farmed salmonids in British Columbia, Canada: 1974–2013. Journal of Fish Diseases 38(8):713–728.
  • Mikalsen AB, Haugland O, Rode M, Solbakk IT, Evensen O. 2012. Atlantic Salmon Reovirus Infection Causes a CD8 T Cell Myocarditis in Atlantic Salmon (Salmo salar L.). PLoS ONE 7(6):e37269.
  • Miller KM, Teffer A, Tucker S, Li S, Schulze AD, Trudel M, Juanes F, Tabata A, Kaukinen KH, Ginther NG, Ming TJ. 2014. Infectious disease, shifting climates, and opportunistic predators: cumulative factors potentially impacting wild salmon declines. Evolutionary Applications 7(7):812–855.
  • Olsen AB, Hjortaas M, Tengs T, Hellberg H, Johansen R. 2015. First description of a new disease in Rainbow Trout (Oncorhynchus mykiss (Walbaum)) similar to Heart and Skeletal Muscle Inflammation (HSMI) and detection of a gene sequence related to Piscine Orthoreovirus (PRV). PLoS One 10:e0131638. DOI:10.1371/journal.pone.0131638
  • Palacios G, Lovoll M, Tengs, T, Hornig, M, Hutchison, S, Hui, J, Kongtorp RT, Savji N, Bussetti AV, Solovyov A, Kristoffersen AB. 2010. Heart and Skeletal Muscle Inflammation of farmed salmon is associated with infection with a novel reovirus. PLOS One 5(7):e11487.
  • Polinski MP, Bradshaw JC, Inkpen SM, Richard JR, Fritsvold C, Poppe TT, Rise ML, Garver KA, Johnson SC. 2016. De novo assembly of Sockeye salmon kidney transcriptomes reveal a limited early response to piscine reovirus with or without infectious hematopoietic necrosis virus superinfection. BMC Genomics (2016) 17:848 DOI 10.1186/s12864-016-3196-y
  • Saddique MA. 2014. Study of the Piscine orthoreovirus (PRV) associated with heart and skeletal muscle inflammation (HSMI) in Atlantic salmon. Msc Thesis, Hedmark University College.
  • Watanabe K, Karlsen M, Devold M, Isdal E, Litlabo A, Nylund A. 2006. Virus-like particles associated with heart and skeletal muscle inflammation (HSMI). Diseases of Aquatic Organisms 70:183–192.
  • Siah A, Morrison DB, Fringuelli E, Savage P, Richmond Z, Johns R, Purcell MK, Johnson SC, Saksida SM. 2015. Piscine reovirus: Genomic and molecular phylogenetic analysis from farmed and wild salmonids collected on the Canada/US Pacific Coast. PLoS ONE 10(11):e0141475.
  • Takano T, Nawata A, Sakai T, Matsuyama T, Ito T, Kurita J, et al. (2016) Full-Genome Sequencing and Confirmation of the Causative Agent of Erythrocytic Inclusion Body Syndrome in Coho Salmon Identifies a New Type of Piscine Orthoreovirus. PLoS ONE 11(10): e0165424. doi:10.1371/journal.pone.0165424
  • Wiik-Nielsen CR, Løvoll M, Sandlund N, Faller, R, Wiik-Nielen, J, Jensen, BB. 2012. First detection of Piscine Reovirus (PRV) in marine fish species. Diseases of Aquatic Organisms 97:255–258.
  • Wiik-Nielson J, Alarcon M, Bang Jensen B, Haugland O, Mikalsen AB. 2016. Viral coinfections in farmed Atlantic salmon, Salmo salar L., displaying myocarditis. Journal of Fish Diseases doi:10.1111/jfd.12487.
  • Yousaf MN, Koppang EO, Skjødt K, Köllner B, Hordvik I, Zou J, Secombes C, Powell MD. 2012. Cardiac pathological changes of Atlantic salmon (Salmo salar L.) affected with heart and skeletal muscle inflammation (HSMI). Fish & Shellfish Immunology 33:305e315.
Date modified: