Host specificity is a phenomenon exhibited by all viruses. For the fish rhabdovirus infectious hematopoietic necrosis virus (IHNV), differential specificity of virus strains from the U and M genogroups has been established both in the field and in experimental challenges. In rainbow trout (), M IHNV strains are consistently more prevalent and more virulent than U IHNV. The basis of the differential ability of these two IHNV genogroups to cause disease in rainbow trout was investigated in live infection challenges with representative U and M IHNV strains. When IHNV was delivered by intraperitoneal injection, the mortality caused by U IHNV increased, indicating that the low virulence of U IHNV is partly due to inefficiency in entering the trout host. Analyses of replication showed that U IHNV consistently had lower prevalence and lower viral load than M IHNV during the course of infection. In analyses of the host immune response, M IHNV-infected fish consistently had higher and longer expression of innate immune-related genes such as . This suggests that the higher virulence of M IHNV is not due to suppression of the immune response in rainbow trout. Taken together, the results support a kinetics hypothesis wherein faster replication enables M IHNV to rapidly achieve a threshold level of virus necessary to override the strong host innate immune response.


Article metrics loading...

Loading full text...

Full text loading...



  1. Amend, D. F., Yasutake, W. T. & Mead, R. W.(1969). A hematopoietic virus disease of rainbow trout and sockeye salmon. Trans Am Fish Soc 98, 796–804.[CrossRef] [Google Scholar]
  2. Anderson, E. D., Engelking, H. M., Emmenegger, E. J. & Kurath, G.(2000). Molecular epidemiology reveals emergence of a virulent infectious hematopoietic necrosis (IHN) virus strain in wild salmon and transmission to hatchery fish. J Aquat Anim Health 12, 85–89.[CrossRef] [Google Scholar]
  3. Batts, W. N. & Winton, J. R.(1989). Enhanced detection of infectious hematopoietic necrosis virus and other fish viruses by pretreatment of cell monolayers with polyethylene glycol. J Aquat Anim Health 1, 284–290.[CrossRef] [Google Scholar]
  4. Bergmann, S. M., Fichtner, D., Skall, H. F., Schlotfeldt, H. J. & Olesen, N. J.(2003). Age- and weight-dependent susceptibility of rainbow trout Oncorhynchus mykiss to isolates of infectious hematopoietic necrosis virus (IHNV) of varying virulence. Dis Aquat Organ 55, 205–210.[CrossRef] [Google Scholar]
  5. Bernard, D., Riteau, B., Hansen, J. D., Phillips, R. B., Michel, F., Boudinot, P. & Benmansour, A.(2006). Costimulatory receptors in a teleost fish: typical CD28, elusive CTLA4. J Immunol 176, 4191–4200.[CrossRef] [Google Scholar]
  6. Boudinot, P., Massin, P., Blanco, M., Riffault, S. & Benmansour, A.(1999).Vig-1, a new fish gene induced by the rhabdovirus glycoprotein, has a virus-induced homologue in humans and shares conserved motifs with the MoaA family. J Virol 73, 1846–1852. [Google Scholar]
  7. Boudinot, P., Salhi, S., Blanco, M. & Benmansour, A.(2001). Viral haemorrhagic septicaemia virus induces vig-2, a new interferon-responsive gene in rainbow trout. Fish Shellfish Immunol 11, 383–397.[CrossRef] [Google Scholar]
  8. Caipang, C. M., Hirono, I. & Aoki, T.(2003).In vitro inhibition of fish rhabdoviruses by Japanese flounder, Paralichthys olivaceus Mx. Virology 317, 373–382.[CrossRef] [Google Scholar]
  9. Chan, S. H., Kobayashi, M., Santoli, D., Perussia, B. & Trinchieri, G.(1992). Mechanisms of IFN-γ induction by natural killer cell stimulatory factor (NKSF/IL-12). Role of transcription and mRNA stability in the synergistic interaction between NKSF and IL-2. J Immunol 148, 92–98. [Google Scholar]
  10. Drolet, B. S., Rohovec, J. S. & Leong, J. C.(1994). The route of entry and progression of infectious haematopoietic necrosis virus in Oncorhynchus mykiss (Walbaum): a sequential immunohistochemical study. J Fish Dis 17, 337–347.[CrossRef] [Google Scholar]
  11. Eaton, W. D.(1990). Anti-viral activity in four species of salmonids following exposure to poly inosinic : cytidylic acid. Dis Aquat Organ 9, 193–198.[CrossRef] [Google Scholar]
  12. Ellis, A. E.(2001). Innate host defense mechanisms of fish against viruses and bacteria. Dev Comp Immunol 25, 827–839.[CrossRef] [Google Scholar]
  13. Emmenegger, E. J. & Kurath, G.(2002). Genetic characterization of infectious hematopoietic necrosis virus of coastal salmonid stocks in Washington state. J Aquat Anim Health 14, 25–34.[CrossRef] [Google Scholar]
  14. Fijan, N., Sulimanovic, D., Bearzotti, M., Muzinic, D., Zwillenberg, L., Chilmonczyk, S., Vautherot, J. F. & De Kinkelin, P.(1983). Some properties of the Epithelioma papulosum cyprini (EPC) cell line from carp Cyprinus carpio. Ann Inst Pasteur Virol 134E, 207–220. [Google Scholar]
  15. Garver, K. A., Troyer, R. M. & Kurath, G.(2003). Two distinct phylogenetic clades of infectious hematopoietic necrosis virus overlap within the Columbia River basin. Dis Aquat Organ 55, 187–203.[CrossRef] [Google Scholar]
  16. Garver, K. A., Batts, W. N. & Kurath, G.(2006). Virulence comparisons of infectious hematopoietic necrosis virus U and M genogroups in Sockeye salmon and Rainbow trout. J Aquat Anim Health 18, 232–243.[CrossRef] [Google Scholar]
  17. Grimm, D., Staeheli, P., Hufbauer, M., Koerner, I., Martínez-Sobrido, L., Solórzano, A., García-Sastre, A., Haller, O. & Kochs, G.(2007). Replication fitness determines high virulence of influenza A virus in mice carrying functional Mx1 resistance gene. Proc Natl Acad Sci U S A 104, 6806–6811.[CrossRef] [Google Scholar]
  18. Harmache, A., LeBerre, M., Droineau, S., Giovannini, M. & Brémont, M.(2006). Bioluminescence imaging of live infected salmonids reveals that the fin bases are the major portal of entry for Novirhabdovirus. J Virol 80, 3655–3659.[CrossRef] [Google Scholar]
  19. Helmick, C. M., Bailey, J. F., LaPatra, S. E. & Ristow, S.(1995). The esophagus/cardiac stomach region: site of attachment and internalization of infectious hematopoietic necrosis virus in challenged juvenile rainbow trout Oncorhynchus mykiss and coho salmon O. kisutch. Dis Aquat Organ 23, 189–199.[CrossRef] [Google Scholar]
  20. Kubin, M., Kamoun, M. & Trinchieri, G.(1994). Interleukin 12 synergizes with B7/CD28 interaction in inducing efficient proliferation and cytokine production of human T cells. J Exp Med 180, 211–222.[CrossRef] [Google Scholar]
  21. Kurath, G., Garver, K. A., Troyer, R. M., Emmenegger, E. J., Einer-Jensen, K. & Anderson, E.(2003). Phylogeography of infectious hematopoietic necrosis virus in North America. J Gen Virol 84, 803–814.[CrossRef] [Google Scholar]
  22. Landis, E. D., Purcell, M. K., Thorgaard, G. H., Wheeler, P. A. & Hansen, J. D.(2008). Transcriptional profiling of MHC class I genes in rainbow trout infected with infectious hematopoietic necrosis virus. Mol Immunol 45, 1646–1657.[CrossRef] [Google Scholar]
  23. LaPatra, S. E., Groberg, W. J., Rohovec, J. S. & Fryer, J. L.(1990). Size-related susceptibility of salmonids to two strains of infectious hematopoietic necrosis virus. Trans Am Fish Soc 119, 25–30.[CrossRef] [Google Scholar]
  24. LaPatra, S. E., Fryer, J. L. & Rohovec, J. S.(1993). Virulence comparison of different electropherotypes of infectious hematopoietic necrosis virus. Dis Aquat Organ 16, 115–120.[CrossRef] [Google Scholar]
  25. LaPatra, S. E., Lauda, K. A. & Jones, G. R.(1994). Antigenic variants of infectious hematopoietic necrosis virus and implications for vaccine development. Dis Aquat Organ 20, 119–126.[CrossRef] [Google Scholar]
  26. Lorenzen, N. & LaPatra, S. E.(1999). Immunity to rhabdoviruses in rainbow trout: the antibody response. Fish Shellfish Immunol 9, 345–360.[CrossRef] [Google Scholar]
  27. McLauchlan, P. E., Collet, B., Ingerslev, E., Secombes, C. J., Lorenzen, N. & Ellis, A. E.(2003). DNA vaccination against viral haemorrhagic septicaemia (VHS) in rainbow trout: size, dose, route of injections and duration of protection – early protection correlates with Mx expression. Fish Shellfish Immunol 15, 39–50.[CrossRef] [Google Scholar]
  28. Murphy, E. E., Terres, G., Macatonia, S. E., Hsieh, C. S., Mattson, J., Lanier, L., Wysocka, M., Trinchieri, G., Murphy, K. & O'Garra, A.(1994). B7 and interleukin 12 cooperate for proliferation and interferon γ production by mouse T helper clones that are unresponsive to B7 costimulation. J Exp Med 180, 223–231.[CrossRef] [Google Scholar]
  29. O'Farrell, C., Vaghefi, N., Cantonnet, M., Buteau, B., Boudinot, P. & Benmansour, A.(2002). Survey of transcript expression in rainbow trout leukocytes reveals a major contribution of interferon-responsive genes in the early response to a rhabdovirus infection. J Virol 76, 8040–8049.[CrossRef] [Google Scholar]
  30. Ooi, E. L., Verjan, N., Haraguchi, I., Oshima, T., Kondo, H., Hirono, I., Aoki, T., Kiyono, H. & Yuki, Y.(2008). Innate immunomodulation with recombinant interferon-α enhances resistance of rainbow trout (Oncorhynchus mykiss) to infectious hematopoietic necrosis virus. Dev Comp Immunol 32, 1211–1220.[CrossRef] [Google Scholar]
  31. Pierce, A. L., Dickey, J. T., Larsen, D. L., Fukada, H., Swanson, P. & Dickhoff, W. W.(2004). A quantitative real-time RT-PCR assay for salmon IGF-I mRNA and its application in the study of GH regulation of IGF-I gene expression in primary culture of salmon hepatocytes. Gen Comp Endocrinol 135, 401–411.[CrossRef] [Google Scholar]
  32. Purcell, M. K., Kurath, G., Garver, K. A., Herwig, R. P. & Winton, J. R.(2004). Quantitative expression profiling of immune response genes in rainbow trout following infectious hematopoietic necrosis virus (IHNV) infection or DNA vaccination. Fish Shellfish Immunol 17, 447–462.[CrossRef] [Google Scholar]
  33. Purcell, M. K., Hart, S. A., Kurath, G. & Winton, J. R.(2006a). Strand-specific, real-time RT-PCR assays for quantification of genomic and positive-sense RNAs of the fish rhabdovirus infectious necrosis virus. J Virol Methods 132, 18–24.[CrossRef] [Google Scholar]
  34. Purcell, M. K., Nichols, K. M., Winton, J. R., Kurath, G., Thorgaard, G. H., Wheeler, P., Hansen, J. D., Herwig, R. P. & Park, L. K.(2006b). Comprehensive gene expression profiling following DNA vaccination of rainbow trout against infectious hematopoietic necrosis virus. Mol Immunol 43, 2089–2106.[CrossRef] [Google Scholar]
  35. Purcell, M. K., Laing, K. J., Woodson, J. C., Thorgaard, G. H. & Hansen, J. D.(2009a). Characterization of the interferon genes in homozygous rainbow trout reveals two novel genes, alternate splicing and differential regulation of duplicated genes. Fish Shellfish Immunol 26, 293–304.[CrossRef] [Google Scholar]
  36. Purcell, M. K., Garver, K. A., Conway, C., Elliott, D. G. & Kurath, G.(2009b). Infectious hematopoietic necrosis virus genogroup-specific virulence mechanisms in sockeye salmon (Oncorhynchus nerka) from Redfish Lake Idaho. J Fish Dis (in press). [Google Scholar]
  37. Rogel-Gaillard, C., Chilmonczyk, S. & de Kinkelin, P.(1993).In vitro induction of interferon-like activity from rainbow trout leucocytes stimulated by Egtved virus. Fish Shellfish Immunol 3, 383–394.[CrossRef] [Google Scholar]
  38. Romero, A., Figueras, A., Tafalla, C., Thoulouze, M. I., Brèmont, M. & Novoa, B.(2005). Histological, serological and virulence studies on rainbow trout experimentally infected with recombinant infectious hematopoietic necrosis viruses. Dis Aquat Organ 68, 17–28.[CrossRef] [Google Scholar]
  39. Saint-Jean, S. R. & Pérez-Prieto, S. I.(2006). Interferon mediated antiviral activity against salmonid fish viruses in BF-2 and other cell lines. Vet Immunol Immunopathol 110, 1–10.[CrossRef] [Google Scholar]
  40. Trobridge, G. D., Chiou, P. P., Kim, C. H. & Leong, J. C.(1997a). Induction of the Mx protein of rainbow trout Oncorhynchus mykissin vitro and in vivo with poly I : C dsRNA and infectious hematopoietic necrosis virus. Dis Aquat Organ 30, 91–98.[CrossRef] [Google Scholar]
  41. Trobridge, G. D., Chiou, P. P. & Leong, J. C.(1997b). Cloning of the rainbow trout (Oncorhynchus mykiss) Mx-2 and Mx3 cDNAs and characterization of trout Mx protein expression in salmon cells. J Virol 71, 5304–5311. [Google Scholar]
  42. Troyer, R. M., LaPatra, S. E. & Kurath, G.(2000). Genetic analyses reveal unusually high diversity of infectious hematopoietic necrosis virus in rainbow trout aquaculture. J Gen Virol 81, 2823–2832. [Google Scholar]
  43. Troyer, R. M., Garver, K. A., Ranson, J. C., Wargo, A. R. & Kurath, G.(2008).In vivo growth competition assays demonstrate equal fitness of fish rhabdovirus strains that co-circulate in aquaculture. Virus Res 137, 179–188.[CrossRef] [Google Scholar]
  44. Wolf, K.(1988). Infectious hematopoietic necrosis virus. In Fish Viruses and Fish Viral Diseases, pp. 83–114. Edited by K. Wolf. Ithaca, NY: Cornell University Press.
  45. Yamamoto, T. & Clermont, T. J.(1990). Multiplication of infectious hematopoietic necrosis virus in rainbow trout following immersion infection: organ assay and electron microscopy. J Aquat Anim Health 2, 261–270.[CrossRef] [Google Scholar]
  46. Yamamoto, T., Batts, W. N., Arakawa, C. K. & Winton, J. R.(1990). Multiplication of infectious hematopoietic necrosis virus in rainbow trout following immersion infection: whole-body assay and immunohistochemistry. J Aquat Anim Health 2, 271–280.[CrossRef] [Google Scholar]
  47. Zou, J., Peddie, S., Scapigliati, G., Zhang, Y., Bols, N. C., Ellis, A. E. & Secombes, C. J.(2003). Functional characterisation of the recombinant tumor necrosis factors in rainbow trout, Oncorhynchus mykiss. Dev Comp Immunol 27, 813–822.[CrossRef] [Google Scholar]

Data & Media loading...


vol. , part 9, pp. 2172–2182

Primer and probe sequences for quantitative PCR analyses [ PDF] (118 KB)


Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error