We research and teach virology.
About the Virology Unit
The research in the Virology Unit is aimed at central viral infections in Norwegian fish farming and cattle production and at viruses that can infect humans through food and water. We are responsible for teaching veterinary and veterinary nursing students in virology.
The research unit has for many years had viral infections in farmed fish as a central focus due to the importance of these infections for the aquaculture industry nationally. The fish virus group (link) has the main focus on Piscint orthoreovirus (PRV) which causes the disease cardiovascular inflammation (HSMB); Salmonid alphavirus (SAV) which is the cause of Pancreatic Disease (PD) and Infectious salmon anemia virus (ILAV). The long-term goal is to understand basic disease mechanisms, ie: «Why does the fish get sick». It can help to establish preventive measures and vaccines to be able to control the infections. «What can be done to prevent disease?»
The Virology Unit has worked with bovine coronavirus (BCoV) for several years, in close collaboration with the Production Animal Clinic at Faculty for Veterinary Medicine at NMBU. BCoV causes intestinal and respiratory infections in cattle and is widespread in Norwegian herds. The research has formed part of the basis for the establishment of the control program for BCoV and BRSV (bovine respiratory syncytial virus).
In the area of food safety, the unit's focus has been on norovirus (NoV), adenovirus (AdV) and hepatitis A virus (HAV). NoV is the most common cause of foodborne illness, both in Norway and globally. Our work has been particularly focused on establishing a methodology for virus detection in food and water. The Virology Unit is the national reference laboratory for viruses in food and water.
The Virology Unit has for several years been the national reference laboratory for viral infections in bees. There is a lot of attention in society around increased mortality in bees. We have shown that Deformed wing viruses (DWV) and Sacbrood viruses (bagpipe viruses) are important for increased mortality in bees in Norway.
We teach veterinary students in virology in the blocks General pathology, Infectious diseases and Food safety, and veterinary students who have specialization in aquaculture. A main goal in the theory of infection is that students gain an understanding of the properties of viruses that are important for the virus' ability to cause disease, what kind of diseases they cause, how they are transmitted, and that they gain knowledge about disease mechanisms, epidemiology and prevention. The focus is on viral infections in production animals (including fish), sports and family animals in Norway, but also on important viral diseases internationally. In food safety, the focus is on NoV and HAV and infection of humans via Norwegian-produced and imported foods.
The teaching of our veterinary nursing students will provide knowledge about viruses in general, cleaning, disinfection, vaccination and about the most important viruses that cause disease in sports and family animals in Norway or that we fear may establish themselves in Norway.
- Virus infection models
- Receptor research
- Reverse genetics
- Replicone vaccines / DNA vaccines
- Next generation sequencing (NGS) of viruses
- RNAseq
- In situ hybridization
- Flow cytometry of virus-infected cells
- Quantification of «live» viruses (culture and PMAxx treatment)
- Virus quantification (qPCR and droplet digital PCR)
- SARS-CoV2 in sewage (NIVA and SLU)
- BarriNor (Norwegian Water and Water Producers)
- NoV in Pacific Oysters (Institute of Marine Research)
- BCoV and Cryptosporidium parvum in vitro co-infection [Department of Parasitology]
- Establishing bovine enteroids for cultivation of enteric pathogens (FG for parasitology)
- APPV in pigs (Production Animal Clinic and SLU)
- Detection of Salmonid Alphavirus in water (Veterinary Institute)
- PlastPath (FG for food safety, FG for pathology and Weltzienlab)
- Hantavirus and hepatitis E virus in rats (FG for bacteriology)
- VivaAct (funded by NFR) Vaccine development fish, (Univ in Tromsø, Veterinary Institute, Technical University of Denmark, INRA France)
- Verification (funded by NFR) Cellular receptor for PRV. (SINTEF, UNiv of Pittsburgh, USA, Miguel Hernández de Elche University, Spain)
- Red Flag (funded by the NFR, headed by the Veterinary Institute). Immunological significance of red blood cells in fish. (Veterinary Institute, Univ of British Columbia, Canada)
- Red and black spots in salmon fillet (funded by FHF) (Expert group for anatomy, Prepat)
- PRV - vaccine candidate. (Funded by Elanco, USA)
- Emergence and spread of PRV-3 (Funded by the Danish Research Council, led by the Technical University of Denmark)
- Expression studies of DNA constructs (Funded by Stonehaven, UK)
- Effect of ISA vaccine (financed by industry)Is PMCV an infection of salmon? (funded by FHF) (Pharmaq Analytic)
- Fresh varroa resistant honey bees (funded by NFR) (Beekeepers' team)
- Management support virus bees (MT
Research in the fish virus group is targeted at key virus infections in Norwegian farming.
Research in the fish virus group is targeted at key virus infections in Norwegian farming. The main focus is on Piscint orthoreovirus (PRV), which causes the disease Heart and skeletal muscle inflammation (HSMI); Salmonid alphavirus which is the cause of Pancreas disease (PD) and Infectious salmon anemia virus (ILAV).
The long-term goal of research into these viruses and the infections they cause is to understand basic disease mechanisms. It can contribute to arriving at preventive measures and vaccines that can be used to effectively control the infections.
The research is to a large extent externally financed (NFR, FHF, Industry). Much activity is directed towards basic research into properties of agents that are important in virus-host interaction, and for innate and acquired response (=immunity). We therefore collaborate with environments that focus on characteristics of host animals (responses in general, morphology, expression analysis etc.) and with special expertise in protein chemistry.
There are about 10 of us in the fish virus group. The research activity is dependent on access to external project funds
10 years ago we published the discovery of a new and unknown virus, PRV. The virus was discovered using NGS, as a new methodology at the time. Since then, we have focused on describing the virus, in terms of distribution, significance for disease development, and functions of the individual viral proteins. PRV is the most widespread virus in Atlantic salmon aquaculture, and it is the cause of heart and skeletal muscle inflammation, which is an important and widespread disease in farmed salmon.
There is no commercial vaccine available against PRV, and the development of a vaccine has been hampered by the fact that the virus cannot be grown in known cell cultures. This stops the classic strategies of virus vaccines and studies of infection. Therefore, much of the research has been carried out using infection models with PRV in salmon. We have found that erythrocytes are the target cells of PRV in salmon, and we have succeeded in purifying virus particles from erythrocytes and from serum.
This has made it possible to study the uptake of the virus in cells. Red blood cells in fish have a nucleus and some intracellular transcription and translation activity, while red blood cells in mammals do not have a nucleus. There are no known viral infections in mammals where the virus replicates in red blood cells. Therefore, PRV has also become a very useful tool for studying the functions of red blood cells in fish, where they have other functions than being pure gas transporters.
An important focus in the next few years will be the identification of the cellular receptor(s) for PRV. This will provide a valuable new tool for vaccine development and possibly also for selective breeding, which may ultimately lead to reducing the incidence of this virus in Atlantic salmon farming. By using expertise from human virology research to promote receptor research on fish viruses, we will create a basic toolbox for studying the key current and future viral diseases in aquaculture.
There has been considerable international interest from other countries where salmon farming is also an important industry. The group's international publications on PRV in recent years can be found here: [1-30].
Pancreas disease is a disease that is notifiable to the OIE. It is widespread in Norwegian farming up to around the Nordland border. In the past, in collaboration with UiB, we have developed reverse genetics for the virus, that is, we can reproduce viruses by transfecting cell cultures with plasmids that contain the entire viral genome. We have further utilized this in the immunization of fish where the structural genes of SAV have been removed and replaced with proteins from other viruses and SAV's replication machinery has been used to express these. These are often called replicon vaccines. We have shown that this provides protection against Infectious salmon anemia and Infectious pancreatic necrosis.
Most virus vaccines in humans and also in sports and family animals are effective and consist of live, weakened viruses, but there are no such attenuated vaccines for salmon. By using the reverse genetics model, we have modified the virus's properties by deglycosylating, that is to say removing sugar molecules, the surface proteins of SAV. When we deglycosylated the protein E1 the virus was no longer infectious, but when we deglycosylated the protein E2 we were able to revive the virus. We also showed that E2 deglycosylated viruses were attenuated in cell culture since they produce less virus and cause less cell damage than intact viruses. However, when E2 deglycosylated viruses were given to salmon they were infectious to others and caused disease. The attenuation observed in cell culture could not be transferred to salmon. Several different living mutants have therefore been developed and will be tested in salmon.
The group's international publications on SAV in recent years can be found here: [31-37]
Pancreas disease is a disease that is notifiable to the OIE. It is widespread in Norwegian farming up to around the Nordland border. In the past, in collaboration with UiB, we have developed reverse genetics for the virus, that is, we can reproduce viruses by transfecting cell cultures with plasmids that contain the entire viral genome. We have further utilized this in the immunization of fish where the structural genes of SAV have been removed and replaced with proteins from other viruses and SAV's replication machinery has been used to express these. These are often called replicon vaccines. We have shown that this provides protection against Infectious salmon anemia and Infectious pancreatic necrosis.
Most virus vaccines in humans and also in sports and family animals are effective and consist of live, weakened viruses, but there are no such attenuated vaccines for salmon. By using the reverse genetics model, we have modified the virus's properties by deglycosylating, that is to say removing sugar molecules, the surface proteins of SAV. When we deglycosylated the protein E1 the virus was no longer infectious, but when we deglycosylated the protein E2 we were able to revive the virus. We also showed that E2 deglycosylated viruses were attenuated in cell culture since they produce less virus and cause less cell damage than intact viruses. However, when E2 deglycosylated viruses were given to salmon they were infectious to others and caused disease. The attenuation observed in cell culture could not be transferred to salmon. Several different living mutants have therefore been developed and will be tested in salmon.
The group's international publications on SAV in recent years can be found here: [31-37]
ISA is also a notifiable disease to the OIE. The virus exists in two forms, ISAV-HPRΔ, which causes classic ILA disease, and ISAV-HPR0, which is apathogenic and cannot be grown in cell culture. ISAV-HPR0 is widespread and is the origin of ISAV-HPRΔ which is only found in connection with disease.
Our research has been directed at ISAV-HPRΔ. In the past, we have tested inactivated whole virus vaccines that provide very good protection, but are too expensive to produce, and also made and tested replicon vaccines against ISA. Our basic research for ISAV in recent years has focused on functions of regulatory viral proteins in the replication cycle of ISAV.
The group's international publications about ISAV in recent years can be found here: [38-43]
- Adamek, M.; Hellmann, J.; Flamm, A.; Teitge, F.; Vendramin, N.; Fey, D.; Risse, K.; Blakey, F.; Rimstad, E.; Steinhagen, D. Detection of piscine orthoreoviruses (prv-1 and prv-3) in atlantic salmon and rainbow trout farmed in germany. Transbound Emerg Dis 2019, 66, 14-21.
- Bjorgen, H.; Haldorsen, R.; Oaland, O.; Kvellestad, A.; Kannimuthu, D.; Rimstad, E.; Koppang, E.O. Melanized focal changes in skeletal muscle in farmed atlantic salmon after natural infection with piscine orthoreovirus (prv). Journal of fish diseases 2019, 42, 935-945.
- Bjorgen, H.; Wessel, O.; Fjelldal, P.G.; Hansen, T.; Sveier, H.; Saebo, H.R.; Enger, K.B.; Monsen, E.; Kvellestad, A.; Rimstad, E., et al. Piscine orthoreovirus (prv) in red and melanised foci in white muscle of atlantic salmon (salmo salar). Veterinary research 2015, 46, 89.
- Dahle, M.K.; Wessel, O.; Timmerhaus, G.; Nyman, I.B.; Jorgensen, S.M.; Rimstad, E.; Krasnov, A. Transcriptome analyses of atlantic salmon (salmo salar l.) erythrocytes infected with piscine orthoreovirus (prv). Fish & shellfish immunology 2015, 45, 780-790.
- Dhamotharan, K.; Bjørgen, H.; Malik, M.; Nyman, I.; Markussen, T.; Dahle, M.; Koppang, E.; Wessel, Ø.; Rimstad, E.J.P. Dissemination of piscine orthoreovirus-1 (prv-1) in atlantic salmon (salmo salar) during the early and regenerating phases of infection. 2020, 9.
- Dhamotharan, K.; Tengs, T.; Wessel, O.; Braaen, S.; Nyman, I.B.; Hansen, E.F.; Christiansen, D.H.; Dahle, M.K.; Rimstad, E.; Markussen, T. Evolution of the piscine orthoreovirus genome linked to emergence of heart and skeletal muscle inflammation in farmed atlantic salmon (salmo salar). Viruses 2019, 11.
- Dhamotharan, K.; Vendramin, N.; Markussen, T.; Wessel, O.; Cuenca, A.; Nyman, I.B.; Olsen, A.B.; Tengs, T.; Krudtaa Dahle, M.; Rimstad, E. Molecular and antigenic characterization of piscine orthoreovirus (prv) from rainbow trout (oncorhynchus mykiss). Viruses 2018, 10.
- Di Cicco, E.; Ferguson, H.W.; Schulze, A.D.; Kaukinen, K.H.; Li, S.; Vanderstichel, R.; Wessel, O.; Rimstad, E.; Gardner, I.A.; Hammell, K.L., et al. Heart and skeletal muscle inflammation (hsmi) disease diagnosed on a british columbia salmon farm through a longitudinal farm study. PloS one 2017, 12, e0171471.
- Finstad, O.W.; Dahle, M.K.; Lindholm, T.H.; Nyman, I.B.; Lovoll, M.; Wallace, C.; Olsen, C.M.; Storset, A.K.; Rimstad, E. Piscine orthoreovirus (prv) infects atlantic salmon erythrocytes. Veterinary research 2014, 45, 35.
- Finstad, O.W.; Falk, K.; Lovoll, M.; Evensen, O.; Rimstad, E. Immunohistochemical detection of piscine reovirus (prv) in hearts of atlantic salmon coincide with the course of heart and skeletal muscle inflammation (hsmi). Veterinary research 2012, 43, 27.
- Haatveit, H.M.; Hodneland, K.; Braaen, S.; Hansen, E.F.; Nyman, I.B.; Dahle, M.K.; Frost, P.; Rimstad, E. DNA vaccine expressing the non-structural proteins of piscine orthoreovirus delay the kinetics of prv infection and induces moderate protection against heart -and skeletal muscle inflammation in atlantic salmon (salmo salar). Vaccine 2018, 36, 7599-7608.
- Haatveit, H.M.; Nyman, I.B.; Markussen, T.; Wessel, O.; Dahle, M.K.; Rimstad, E. The non-structural protein muns of piscine orthoreovirus (prv) forms viral factory-like structures. Veterinary research 2016, 47, 5.
- Haatveit, H.M.; Wessel, O.; Markussen, T.; Lund, M.; Thiede, B.; Nyman, I.B.; Braaen, S.; Dahle, M.K.; Rimstad, E. Viral protein kinetics of piscine orthoreovirus infection in atlantic salmon blood cells. Viruses 2017, 9.
- Johansen, L.H.; Dahle, M.K.; Wessel, O.; Timmerhaus, G.; Lovoll, M.; Rosaeg, M.; Jorgensen, S.M.; Rimstad, E.; Krasnov, A. Differences in gene expression in atlantic salmon parr and smolt after challenge with piscine orthoreovirus (prv). Molecular immunology 2016, 73, 138-150.
- Lund, M.; Krudtaa Dahle, M.; Timmerhaus, G.; Alarcon, M.; Powell, M.; Aspehaug, V.; Rimstad, E.; Jorgensen, S.M. Hypoxia tolerance and responses to hypoxic stress during heart and skeletal muscle inflammation in atlantic salmon (salmo salar). PloS one 2017, 12, e0181109.
- Lund, M.; Rosaeg, M.V.; Krasnov, A.; Timmerhaus, G.; Nyman, I.B.; Aspehaug, V.; Rimstad, E.; Dahle, M.K. Experimental piscine orthoreovirus infection mediates protection against pancreas disease in atlantic salmon (salmo salar). Veterinary research 2016, 47, 107.
- Malik, M.S.; Bjorgen, H.; Dhamotharan, K.; Wessel, O.; Koppang, E.O.; Di Cicco, E.; Hansen, E.F.; Dahle, M.K.; Rimstad, E. Erythroid progenitor cells in atlantic salmon (salmo salar) may be persistently and productively infected with piscine orthoreovirus (prv). Viruses 2019, 11.
- Markussen, T.; Dahle, M.K.; Tengs, T.; Lovoll, M.; Finstad, O.W.; Wiik-Nielsen, C.R.; Grove, S.; Lauksund, S.; Robertsen, B.; Rimstad, E. Sequence analysis of the genome of piscine orthoreovirus (prv) associated with heart and skeletal muscle inflammation (hsmi) in atlantic salmon (salmo salar). PloS one 2013, 8, e70075.
- Palacios, G.; Lovoll, M.; Tengs, T.; Hornig, M.; Hutchison, S.; Hui, J.; Kongtorp, R.T.; Savji, N.; Bussetti, A.V.; Solovyov, A., et al. Heart and skeletal muscle inflammation of farmed salmon is associated with infection with a novel reovirus. PloS one 2010, 5, e11487.
- Rosaeg, M.V.; Lund, M.; Nyman, I.B.; Markussen, T.; Aspehaug, V.; Sindre, H.; Dahle, M.K.; Rimstad, E. Immunological interactions between piscine orthoreovirus and salmonid alphavirus infections in atlantic salmon. Fish & shellfish immunology 2017, 64, 308-319.
- Teige, L.H.; Lund, M.; Haatveit, H.M.; Rosaeg, M.V.; Wessel, O.; Dahle, M.K.; Storset, A.K. A bead based multiplex immunoassay detects piscine orthoreovirus specific antibodies in atlantic salmon (salmo salar). Fish & shellfish immunology 2017, 63, 491-499.
- Tengs, T.; Rimstad, E. Emerging pathogens in the fish farming industry and sequencing-based pathogen discovery. Developmental and comparative immunology 2017, 75, 109-119.
- Vendramin, N.; Alencar, A.L.F.; Iburg, T.M.; Dahle, M.K.; Wessel, O.; Olsen, A.B.; Rimstad, E.; Olesen, N.J. Piscine orthoreovirus infection in atlantic salmon (salmo salar) protects against subsequent challenge with infectious hematopoietic necrosis virus (ihnv). Veterinary research 2018, 49, 30.
- Vendramin, N.; Cuenca, A.; Sorensen, J.; Alencar, A.L.F.; Christiansen, D.H.; Jacobsen, J.A.; Axen, C.; Lieffrig, F.; Ruane, N.M.; Martin, P., et al. Presence and genetic variability of piscine orthoreovirus genotype 1 (prv-1) in wild salmonids in northern europe and north atlantic ocean. Journal of fish diseases 2019.
- Vendramin, N.; Dhamotharan, K.; Olsen, A.B.; Cuenca, A.; Teige, L.H.; Wessel, O.; Iburg, T.M.; Dahle, M.K.; Rimstad, E.; Olesen, N.J. Piscine orthoreovirus subtype 3 (prv-3) causes heart inflammation in rainbow trout (oncorhynchus mykiss). Veterinary research 2019.
- Wessel, O.; Braaen, S.; Alarcon, M.; Haatveit, H.; Roos, N.; Markussen, T.; Tengs, T.; Dahle, M.K.; Rimstad, E. Infection with purified piscine orthoreovirus demonstrates a causal relationship with heart and skeletal muscle inflammation in atlantic salmon. PloS one 2017, 12, e0183781.
- Wessel, O.; Haugland, O.; Rode, M.; Fredriksen, B.N.; Dahle, M.K.; Rimstad, E. Inactivated piscine orthoreovirus vaccine protects against heart and skeletal muscle inflammation in atlantic salmon. Journal of fish diseases 2018, 41, 1411-1419.
- Wessel, O.; Krasnov, A.; Timmerhaus, G.; Rimstad, E.; Dahle, M.K. Antiviral responses and biological concequences of piscine orthoreovirus infection in salmonid erythrocytes. Frontiers in immunology 2018, 9, 3182.
- Wessel, O.; Nyman, I.B.; Markussen, T.; Dahle, M.K.; Rimstad, E. Piscine orthoreovirus (prv) o3 protein binds dsrna. Virus research 2015, 198, 22-29.
- Wessel, O.; Olsen, C.M.; Rimstad, E.; Dahle, M.K. Piscine orthoreovirus (prv) replicates in atlantic salmon (salmo salar l.) erythrocytes ex vivo. Veterinary research 2015, 46, 26.
- Abdullah, A.; Olsen, C.M.; Hodneland, K.; Rimstad, E. A polyprotein-expressing salmonid alphavirus replicon induces modest protection in atlantic salmon (salmo salar) against infectious pancreatic necrosis. Viruses 2015, 7, 252-267.
- Hikke, M.C.; Braaen, S.; Villoing, S.; Hodneland, K.; Geertsema, C.; Verhagen, L.; Frost, P.; Vlak, J.M.; Rimstad, E.; Pijlman, G.P. Salmonid alphavirus glycoprotein e2 requires low temperature and e1 for virion formation and induction of protective immunity. Vaccine 2014, 32, 6206-6212.
- Karlsen, M.; Villoing, S.; Ottem, K.F.; Rimstad, E.; Nylund, A. Development of infectious cdna clones of salmonid alphavirus subtype 3. BMC research notes 2010, 3, 241.
- Karlsen, M.; Villoing, S.; Rimstad, E.; Nylund, A. Characterization of untranslated regions of the salmonid alphavirus 3 (sav3) genome and construction of a sav3 based replicon. Virology journal 2009, 6, 173.
- Karlsen, M.; Yousaf, M.N.; Villoing, S.; Nylund, A.; Rimstad, E. The amino terminus of the salmonid alphavirus capsid protein determines subcellular localization and inhibits cellular proliferation. Archives of virology 2010, 155, 1281-1293.
- Wolf, A.; Hodneland, K.; Frost, P.; Braaen, S.; Rimstad, E. A hemagglutinin-esterase-expressing salmonid alphavirus replicon protects atlantic salmon (salmo salar) against infectious salmon anemia (isa). Vaccine 2013, 31, 661-669.
- Wolf, A.; Hodneland, K.; Frost, P.; Hoeijmakers, M.; Rimstad, E. Salmonid alphavirus-based replicon vaccine against infectious salmon anemia (isa): Impact of immunization route and interactions of the replicon vector. Fish & shellfish immunology 2014, 36, 383-392.
- Lauscher, A.; Krossoy, B.; Frost, P.; Grove, S.; Konig, M.; Bohlin, J.; Falk, K.; Austbo, L.; Rimstad, E. Immune responses in atlantic salmon (salmo salar) following protective vaccination against infectious salmon anemia (isa) and subsequent isa virus infection. Vaccine 2011, 29, 6392-6401.
- Olsen, C.M.; Braaen, S.; Falk, K.; Rimstad, E. Multiple passage of infectious salmon anaemia virus in rainbow trout, oncorhynchus mykiss (walbaum), did not induce increased virus load. Journal of fish diseases 2012, 35, 827-838.
- Olsen, C.M.; Markussen, T.; Thiede, B.; Rimstad, E. Infectious salmon anaemia virus (isav) rna binding protein encoded by segment 8 orf2 and its interaction with isav and intracellular proteins. Viruses 2016, 8.
- Ramly, R.B.; Olsen, C.M.; Braaen, S.; Hansen, E.F.; Rimstad, E. Transcriptional regulation of gene expression of infectious salmon anaemia virus segment 7. Virus research 2014, 190, 69-74.
- Ramly, R.B.; Olsen, C.M.; Braaen, S.; Rimstad, E. Infectious salmon anaemia virus nuclear export protein is encoded by a spliced gene product of genomic segment 7. Virus research 2013, 177, 1-10.
- Rimstad, E.; Markussen, T.J.J.O.A.M. Infectious salmon anaemia virus-molecular biology and pathogenesis of the infection. 2020.