1887

Abstract

Salmon pancreas disease virus (SPDV) also referred to as salmonid alphavirus (SAV) is a virus causing pancreas disease in Atlantic salmon ( L.) and rainbow trout (). Although the virus causes an economically important disease, relatively few full-length genome sequences of SAV strains are currently available. Here, we report full-length genome sequences of nine SAV3 strains from sites farming Atlantic salmon geographically spread along the Norwegian coastline. The virus genomes were sequenced directly from infected heart tissue, to avoid culture selection bias. Sequence analysis confirmed a high level of sequence identity within SAV3 strains, with a mean nucleotide diversity of 0.11 %. Sequence divergence was highest in 6K and E2, while lowest in the capsid protein and the non-structural proteins (nsP4 and nsP2). This study reports for the first time that numerous defective viruses containing genome deletions are generated during natural infection with SAV. Deletions occurred in all virus strains and were not distributed randomly throughout the genome but instead tended to aggregate in certain areas. We suggest imprecise homologous recombination as an explanation for generation of defective viruses with genome deletions. The presence of such viruses, provides a possible explanation for the difficulties in isolating SAV in cell culture. Primary virus isolation was successfully achieved for only two of eight strains, despite extensive attempts using three different cell lines. Both SAV isolates were easily propagated further and concomitant viral deletion mutants present in clinically infected heart tissue were maintained following serial passage in CHH-1 cells.

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2013-09-01
2019-10-15
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References

  1. Baird H. A. , Galetto R. , Gao Y. , Simon-Loriere E. , Abreha M. , Archer J. , Fan J. , Robertson D. L. , Arts E. J. , Negroni M. . ( 2006; ). Sequence determinants of breakpoint location during HIV-1 intersubtype recombination. . Nucleic Acids Res 34:, 5203–5216. [CrossRef] [PubMed]
    [Google Scholar]
  2. Bråve A. , Ljungberg K. , Wahren B. , Liu M. A. . ( 2007; ). Vaccine delivery methods using viral vectors. . Mol Pharm 4:, 18–32. [CrossRef] [PubMed]
    [Google Scholar]
  3. Castric J. , Baudin-Laurencin F. , Brèmont M. , Le Ven A. , Bèarzotti M. . ( 1997; ). Isolation of the virus responsible for sleeping-disease in experimentally infected rainbow-trout Oncorhynchus Mykiss. . Bull Eur Assoc Fish Pathol 17:, 27–30.
    [Google Scholar]
  4. Durden L. A. , Linthicum K. J. , Turell M. J. . ( 1992; ). Mechanical transmission of Venezuelan equine encephalomyelitis virus by hematophagous mites (Acari). . J Med Entomol 29:, 118–121.[PubMed] [CrossRef]
    [Google Scholar]
  5. Edgar R. C. . ( 2004; ). MUSCLE: multiple sequence alignment with high accuracy and high throughput. . Nucleic Acids Res 32:, 1792–1797. [CrossRef] [PubMed]
    [Google Scholar]
  6. Forrester N. L. , Guerbois M. , Adams A. P. , Liang X. , Weaver S. C. . ( 2011; ). Analysis of intrahost variation in Venezuelan equine encephalitis virus reveals repeated deletions in the 6-kilodalton protein gene. . J Virol 85:, 8709–8717. [CrossRef] [PubMed]
    [Google Scholar]
  7. Fringuelli E. , Rowley H. M. , Wilson J. C. , Hunter R. , Rodger H. , Graham D. A. . ( 2008; ). Phylogenetic analyses and molecular epidemiology of European salmonid alphaviruses (SAV) based on partial E2 and nsP3 gene nucleotide sequences. . J Fish Dis 31:, 811–823. [CrossRef] [PubMed]
    [Google Scholar]
  8. García-Arriaza J. , Manrubia S. C. , Toja M. , Domingo E. , Escarmís C. . ( 2004; ). Evolutionary transition toward defective RNAs that are infectious by complementation. . J Virol 78:, 11678–11685. [CrossRef] [PubMed]
    [Google Scholar]
  9. Graham D. A. , Wilson C. , Jewhurst H. , Rowley H. . ( 2008; ). Cultural characteristics of salmonid alphaviruses–influence of cell line and temperature. . J Fish Dis 31:, 859–868. [CrossRef] [PubMed]
    [Google Scholar]
  10. Graham D. A. , Fringuelli E. , Wilson C. , Rowley H. M. , Brown A. , Rodger H. , McLoughlin M. F. , McManus C. , Casey E. . & other authors ( 2010; ). Prospective longitudinal studies of salmonid alphavirus infections on two Atlantic salmon farms in Ireland; evidence for viral persistence. . J Fish Dis 33:, 123–135. [CrossRef] [PubMed]
    [Google Scholar]
  11. Graham D. A. , Frost P. , McLaughlin K. , Rowley H. M. , Gabestad I. , Gordon A. , McLoughlin M. F. . ( 2011; ). A comparative study of marine salmonid alphavirus subtypes 1-6 using an experimental cohabitation challenge model. . J Fish Dis 34:, 273–286. [CrossRef] [PubMed]
    [Google Scholar]
  12. Graham D. A. , Fringuelli E. , Rowley H. M. , Cockerill D. , Cox D. I. , Turnbull T. , Rodger H. , Morris D. , Mc Loughlin M. F. . ( 2012; ). Geographical distribution of salmonid alphavirus subtypes in marine farmed Atlantic salmon, Salmo salar L., in Scotland and Ireland. . J Fish Dis 35:, 755–765. [CrossRef] [PubMed]
    [Google Scholar]
  13. Griffin D. E. . ( 2007; ). Alphaviruses. . In Virology, 5th edn , pp. 1023–1067. Edited by Knipe M. , Howley M. . . Philadelphia:: Lippincott Williams & Wilkins;.
    [Google Scholar]
  14. Guindon S. , Delsuc F. , Dufayard J. F. , Gascuel O. . ( 2009; ). Estimating maximum likelihood phylogenies with PhyML. . Methods Mol Biol 537:, 113–137. [CrossRef] [PubMed]
    [Google Scholar]
  15. Hahn C. S. , Lustig S. , Strauss E. G. , Strauss J. H. . ( 1988; ). Western equine encephalitis virus is a recombinant virus. . Proc Natl Acad Sci U S A 85:, 5997–6001. [CrossRef] [PubMed]
    [Google Scholar]
  16. Hjortaas M. J. , Skjelstad H. R. , Taksdal T. , Olsen A. B. , Johansen R. , Bang-Jensen B. , Ørpetveit I. , Sindre H. . ( 2013; ). The first detections of subtype 2-related salmonid alphavirus (SAV2) in Atlantic salmon, Salmo salar L., in Norway. . J Fish Dis 36:, 71–74. [CrossRef] [PubMed]
    [Google Scholar]
  17. Hodneland K. , Bratland A. , Christie K. E. , Endresen C. , Nylund A. . ( 2005; ). New subtype of salmonid alphavirus (SAV), Togaviridae, from Atlantic salmon Salmo salar and rainbow trout Oncorhynchus mykiss in Norway. . Dis Aquat Organ 66:, 113–120. [CrossRef] [PubMed]
    [Google Scholar]
  18. Jansen M. D. , Gjerset B. , Modahl I. , Bohlin J. . ( 2010; ). Molecular epidemiology of salmonid alphavirus (SAV) subtype 3 in Norway. . Virol J 7:, 188. [CrossRef] [PubMed]
    [Google Scholar]
  19. Karlsen M. , Hodneland K. , Endresen C. , Nylund A. . ( 2006; ). Genetic stability within the Norwegian subtype of salmonid alphavirus (family Togaviridae). . Arch Virol 151:, 861–874. [CrossRef] [PubMed]
    [Google Scholar]
  20. Kumaria R. , Iyer L. R. , Hibberd M. L. , Simões E. A. , Sugrue R. J. . ( 2011; ). Whole genome characterization of non-tissue culture adapted HRSV strains in severely infected children. . Virol J 8:, 372. [CrossRef] [PubMed]
    [Google Scholar]
  21. Lai M. M. . ( 1992; ). RNA recombination in animal and plant viruses. . Microbiol Rev 56:, 61–79.[PubMed]
    [Google Scholar]
  22. Lazzarini R. A. , Keene J. D. , Schubert M. . ( 1981; ). The origins of defective interfering particles of the negative-strand RNA viruses. . Cell 26:, 145–154. [CrossRef] [PubMed]
    [Google Scholar]
  23. Linn M. L. , Aaskov J. G. , Suhrbier A. . ( 1996; ). Antibody-dependent enhancement and persistence in macrophages of an arbovirus associated with arthritis. . J Virol 77:, 407–411. [CrossRef]
    [Google Scholar]
  24. López-Dóriga M. V. , Smail D. A. , Smith R. J. , Doménech A. , Castric J. , Smith P. D. , Ellis A. E. . ( 2001; ). Isolation of salmon pancreas disease virus (SPDV) in cell culture and its ability to protect against infection by the ‘wild-type’ agent. . Fish Shellfish Immunol 11:, 505–522. [CrossRef] [PubMed]
    [Google Scholar]
  25. McLoughlin M. F. , Graham D. A. . ( 2007; ). Alphavirus infections in salmonids–a review. . J Fish Dis 30:, 511–531. [CrossRef] [PubMed]
    [Google Scholar]
  26. McLoughlin M. F. , Nelson R. T. , Rowley H. M. , Cox D. I. , Grant A. N. . ( 1996; ). Experimental pancreas disease in Atlantic salmon Salmo salar post-smolts induced by salmon pancreas disease virus (SPDV).. Dis Aquat Organ 26, 117–124.[CrossRef]
    [Google Scholar]
  27. McLoughlin M. F. , Graham D. A. , Norris A. , Matthews D. , Foyle L. , Rowley H. M. , Jewhurst H. , MacPhee J. , Todd D. . ( 2006; ). Virological, serological and histopathological evaluation of fish strain susceptibility to experimental infection with salmonid alphavirus. . Dis Aquat Organ 72:, 125–133. [CrossRef] [PubMed]
    [Google Scholar]
  28. McVicar A. H. . ( 1987; ). Pancreas disease of farmed Atlantic Salmon, Salmo salar, in Scotland: epidemiology and early pathology. . Aquaculture 67:, 71–78. [CrossRef]
    [Google Scholar]
  29. Munang’andu H. M. , Fredriksen B. N. , Mutoloki S. , Brudeseth B. , Kuo T. Y. , Marjara I. S. , Dalmo R. A. , Evensen O. . ( 2012; ). Comparison of vaccine efficacy for different antigen delivery systems for infectious pancreatic necrosis virus vaccines in Atlantic salmon (Salmo salar L.) in a cohabitation challenge model. . Vaccine 30:, 4007–4016. [CrossRef] [PubMed]
    [Google Scholar]
  30. Nelson R. T. , McLoughlin M. F. , Rowley H. M. , Platten M. A. , Mccormick J. I. . ( 1995; ). Isolation of a toga-like virus from farmed Atlantic salmon Salmo salar with pancreas disease. . Dis Aquat Organ 22:, 25–32. [CrossRef]
    [Google Scholar]
  31. Noppornpanth S. , Smits S. L. , Lien T. X. , Poovorawan Y. , Osterhaus A. D. , Haagmans B. L. . ( 2007; ). Characterization of hepatitis C virus deletion mutants circulating in chronically infected patients. . J Virol 81:, 12496–12503. [CrossRef] [PubMed]
    [Google Scholar]
  32. Paradis E. , Claude J. , Strimmer K. . ( 2004; ). APE: Analyses of Phylogenetics and Evolution in R language. . Bioinformatics 20:, 289–290. [CrossRef] [PubMed]
    [Google Scholar]
  33. Pesko K. N. , Fitzpatrick K. A. , Ryan E. M. , Shi P. Y. , Zhang B. , Lennon N. J. , Newman R. M. , Henn M. R. , Ebel G. D. . ( 2012; ). Internally deleted WNV genomes isolated from exotic birds in New Mexico: function in cells, mosquitoes, and mice. . Virology 427:, 10–17. [CrossRef] [PubMed]
    [Google Scholar]
  34. Petterson E. , Sandberg M. , Santi N. . ( 2009; ). Salmonid alphavirus associated with Lepeophtheirus salmonis (Copepoda: Caligidae) from Atlantic salmon, Salmo salar L. . J Fish Dis 32:, 477–479. [CrossRef] [PubMed]
    [Google Scholar]
  35. Poidinger M. , Coelen R. J. , Mackenzie J. S. . ( 1991; ). Persistent infection of Vero cells by the flavivirus Murray Valley encephalitis virus. . J Gen Virol 72:, 573–578. [CrossRef] [PubMed]
    [Google Scholar]
  36. R Development Core Team ( 2010; ). R: A Language and Environment for Statistical Computing. Vienna:: Foundation for Statistical Computing;.
    [Google Scholar]
  37. Roux L. , Simon A. E. , Holland J. J. . ( 1991; ). Effects of defective interfering viruses on virus replication and pathogenesis in vitro and in vivo. . Adv Virus Res 40:, 181–211. [CrossRef] [PubMed]
    [Google Scholar]
  38. Rowley H. M. , Doherty C. E. , McLoughlin M. F. , Welsh M. D. . ( 1998; ). Isolation of salmon pancreas disease virus (SPDV) from farmed Atlantic salmon, Salmo salar L., in Scotland. . J Fish Dis 21:, 469–472. [CrossRef]
    [Google Scholar]
  39. Schlesinger S. , Weiss B. G. . ( 1994; ). Recombination between Sindbis virus RNAs. . Arch Virol Suppl 9:, 213–220.[PubMed]
    [Google Scholar]
  40. Simon-Loriere E. , Holmes E. C. . ( 2011; ). Why do RNA viruses recombine?. Nat Rev Microbiol 9:, 617–626. [CrossRef] [PubMed]
    [Google Scholar]
  41. Smerdou C. , Liljeström P. . ( 1999; ). Non-viral amplification systems for gene transfer: vectors based on alphaviruses. . Curr Opin Mol Ther 1:, 244–251.[PubMed]
    [Google Scholar]
  42. Söding J. , Lupas A. N. . ( 2003; ). More than the sum of their parts: on the evolution of proteins from peptides. . Bioessays 25:, 837–846. [CrossRef] [PubMed]
    [Google Scholar]
  43. Stauffer Thompson K. A. , Rempala G. A. , Yin J. . ( 2009; ). Multiple-hit inhibition of infection by defective interfering particles. . J Gen Virol 90:, 888–899. [CrossRef] [PubMed]
    [Google Scholar]
  44. Tsai K. N. , Tsang S. F. , Huang C. H. , Chang R. Y. . ( 2007; ). Defective interfering RNAs of Japanese encephalitis virus found in mosquito cells and correlation with persistent infection. . Virus Res 124:, 139–150. [CrossRef] [PubMed]
    [Google Scholar]
  45. Weiss B. , Levis R. , Schlesinger S. . ( 1983; ). Evolution of virus and defective-interfering RNAs in BHK cells persistently infected with Sindbis virus. . J Virol 48:, 676–684.[PubMed]
    [Google Scholar]
  46. Weston J. H. , Welsh M. D. , McLoughlin M. F. , Todd D. . ( 1999; ). Salmon pancreas disease virus, an alphavirus infecting farmed Atlantic salmon, Salmo salar L. . Virology 256:, 188–195. [CrossRef] [PubMed]
    [Google Scholar]
  47. Weston J. , Villoing S. , Brémont M. , Castric J. , Pfeffer M. , Jewhurst V. , McLoughlin M. , Rødseth O. , Christie K. E. . & other authors ( 2002; ). Comparison of two aquatic alphaviruses, salmon pancreas disease virus and sleeping disease virus, by using genome sequence analysis, monoclonal reactivity, and cross-infection. . J Virol 76:, 6155–6163. [CrossRef] [PubMed]
    [Google Scholar]
  48. Weston J. H. , Graham D. A. , Branson E. , Rowley H. M. , Walker I. W. , Jewhurst V. A. , Jewhurst H. L. , Todd D. . ( 2005; ). Nucleotide sequence variation in salmonid alphaviruses from outbreaks of salmon pancreas disease and sleeping disease. . Dis Aquat Organ 66:, 105–111. [CrossRef] [PubMed]
    [Google Scholar]
  49. Xu C. , Guo T. C. , Mutoloki S. , Haugland Ø. , Marjara I. S. , Evensen Ø. . ( 2010; ). Alpha interferon and not gamma interferon inhibits salmonid alphavirus subtype 3 replication in vitro. . J Virol 84:, 8903–8912. [CrossRef] [PubMed]
    [Google Scholar]
  50. Xu C. , Guo T. C. , Mutoloki S. , Haugland Ø. , Evensen Ø. . ( 2012; ). Gene expression studies of host response to Salmonid alphavirus subtype 3 experimental infections in Atlantic salmon. . Vet Res 43:, 78. [CrossRef] [PubMed]
    [Google Scholar]
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