Influenza Virus pp 127-146

Part of the Methods in Molecular Biology book series (MIMB, volume 865) | Cite as

Animal Models

  • Edwin J. B. Veldhuis Kroeze
  • Thijs Kuiken
  • Albert D. M. E. Osterhaus
Protocol

Abstract

Five well-established animal models in influenza research are discussed in a schematic fashion. Although there are clear parallels between these models, like viruses used, housing and handling conditions under biosafety conditions, routes of virus inoculation, sampling strategies, and necropsy techniques (mostly elaborated on in Subheading 4), each of these models involves specific differences in their practical applicability that need thorough assessment depending on the scientific question raised. In other words, there is no universal animal model for influenza and depending on the actual question to be answered the model and the experimental conditions should be carefully selected.

Key words

Influenza Animal model Mouse Ferret Guinea pig Macaque Chicken Duck Methods 

References

  1. 1.
    Herfst, S., Chutinimitkul, S., Ye, J., de Wit, E., Munster, V.J., Schrauwen, E.J., Bestebroer, T.M., Jonges, M., Meijer, A., Koopmans, M., Rimmelzwaan, G.F., Osterhaus, A.D., Perez, D.R. and Fouchier, R.A. (2010) Introduction of virulence markers in PB2 of pandemic swine-origin influenza virus does not result in enhanced virulence or transmission. J. Virol. 84, 3752–3758.PubMedCrossRefGoogle Scholar
  2. 2.
    Munster, V.J., de Wit, E., van Riel, D., Beyer, W.E., Rimmelzwaan, G.F., Osterhaus, A.D., Kuiken, T. and Fouchier, R.A. (2007) The molecular basis of the pathogenicity of the Dutch highly pathogenic human influenza A H7N7 viruses. J. Infect. Dis. 196, 258–265.PubMedCrossRefGoogle Scholar
  3. 3.
    de Wit, E., Munster, V.J., Spronken, M.I., Bestebroer, T.M., Baas, C., Beyer, W.E., Rimmelzwaan, G.F., Osterhaus, A.D. and Fouchier, R.A. (2005) Protection of mice against lethal infection with highly pathogenic H7N7 influenza A virus by using a recombinant low-pathogenicity vaccine strain. J. Virol. 79, 12401–12407.PubMedCrossRefGoogle Scholar
  4. 4.
    Bodewes, R., Kreijtz, J.H., Baas, C., Geelhoed-Mieras, M.M., de Mutsert, G., van Amerongen, G., van den Brand, J.M., Fouchier, R.A., Osterhaus, A.D. and Rimmelzwaan, G.F. (2009) Vaccination against human influenza A/H3N2 virus prevents the induction of heterosubtypic immunity against lethal infection with avian influenza A/H5N1 virus. PLoS One 4, e5538.PubMedCrossRefGoogle Scholar
  5. 5.
    Kreijtz, J.H., Suezer, Y., de Mutsert, G., van Amerongen, G., Schwantes, A., van den Brand, J.M., Fouchier, R.A., Löwer, J., Osterhaus, A.D., Sutter, G. and Rimmelzwaan, G.F. (2009) MVA-based H5N1 vaccine affords cross-clade protection in mice against influenza A/H5N1 viruses at low doses and after single immunization. PLoS One 4, e7790.PubMedCrossRefGoogle Scholar
  6. 6.
    Kreijtz, J.H., Bodewes, R., van den Brand, J.M., de Mutsert, G., Baas, C., van Amerongen, G., Fouchier, R.A., Osterhaus, A.D. and Rimmelzwaan, G.F. (2009) Infection of mice with a human influenza A/H3N2 virus induces protective immunity against lethal infection with influenza A/H5N1 virus. Vaccine 27, 4983–4989.PubMedCrossRefGoogle Scholar
  7. 7.
    Kreijtz, J.H., Suezer, Y., van Amerongen, G., de Mutsert, G., Schnierle, B.S., Wood, J.M., Kuiken, T., Fouchier, R.A., Lower, J., Osterhaus, A.D., Sutter, G. and Rimmelzwaan, G.F. (2007) Recombinant modified vaccinia virus Ankara-based vaccine induces protective immunity in mice against infection with influenza virus H5N1. J. Infect. Dis. 195, 1598–1606.PubMedCrossRefGoogle Scholar
  8. 8.
    Kreijtz, J.H., Bodewes, R., van Amerongen, G., Kuiken, T., Fouchier, R.A., Osterhaus, A.D. and Rimmelzwaan, G.F. (2007) Primary influenza A virus infection induces cross-protective immunity against a lethal infection with a heterosubtypic virus strain in mice. Vaccine 25, 612–620.PubMedCrossRefGoogle Scholar
  9. 9.
    Bodewes, R., Kreijtz, J.H., van Amerongen, G., Geelhoed-Mieras, M.M., Verburgh, R.J., Heldens, J.G., Bedwell, J., van den Brand, J.M., Kuiken, T., van Baalen, C.A., Fouchier, R.A., Osterhaus, A.D. and Rimmelzwaan, G.F. (2010) A single immunization with CoVaccine HT-adjuvanted H5N1 influenza vaccine induces protective cellular and humoral immune responses in ferrets. J. Virol. 84, 7943–7953.Google Scholar
  10. 10.
    van den Brand, J.M., Stittelaar, K.J., van Amerongen, G., Rimmelzwaan, G.F., Simon, J., de Wit, E., Munster, V., Bestebroer, T., Fouchier, R.A., Kuiken, T. and Osterhaus, A.D. (2010) Severity of pneumonia due to new H1N1 influenza virus in ferrets is intermediate between that due to seasonal H1N1 virus and highly pathogenic avian influenza H5N1 virus. J. Infect. Dis. 201, 993–999.PubMedCrossRefGoogle Scholar
  11. 11.
    Friesen, R.H., Koudstaal, W., Koldijk, M.H., Weverling, G.J., Brakenhoff, J.P., Lenting, P.J., Stittelaar, K.J., Osterhaus, A.D., Kompier, R. and Goudsmit, J. (2010) New class of monoclonal antibodies against severe influenza: prophylactic and therapeutic efficacy in ferrets. PLoS One 5, e9106.PubMedCrossRefGoogle Scholar
  12. 12.
    Munster, V.J., de Wit, E., van den Brand, J.M., Herfst, S., Schrauwen, E.J., Bestebroer, T.M., van de Vijver, D., Boucher, C.A., Koopmans, M., Rimmelzwaan, G.F., Kuiken, T., Osterhaus, A.D. and Fouchier, R.A. (2009) Pathogenesis and transmission of swine-origin 2009 A(H1N1) influenza virus in ferrets. Science 325, 481–483.PubMedGoogle Scholar
  13. 13.
    Kreijtz, J.H., Suezer, Y., de Mutsert, G., van den Brand, J.M., van Amerongen, G., Schnierle, B.S., Kuiken, T., Fouchier, R.A., Löwer, J., Osterhaus, A.D., Sutter, G. and Rimmelzwaan, G.F. (2009) Preclinical evaluation of a modified vaccinia virus Ankara (MVA)-based vaccine against influenza A/H5N1 viruses. Vaccine 27, 6296–6299.PubMedCrossRefGoogle Scholar
  14. 14.
    Baras, B., Stittelaar, K.J., Simon, J.H., Thoolen, R.J., Mossman, S.P., Pistoor, F.H., van Amerongen, G., Wettendorff, M.A., Hanon, E. and Osterhaus, A.D. (2008) Cross-protection against lethal H5N1 challenge in ferrets with an adjuvanted pandemic influenza vaccine. PLoS One 3, e1401.PubMedCrossRefGoogle Scholar
  15. 15.
    Kreijtz, J.H., Suezer, Y., de Mutsert, G., van den Brand, J.M., van Amerongen, G., Schnierle, B.S., Kuiken, T., Fouchier, R.A., Löwer, J., Osterhaus, A.D., Sutter, G. and Rimmelzwaan, G.F. (2009) Recombinant modified vaccinia virus Ankara expressing the hemagglutinin gene confers protection against homologous and heterologous H5N1 influenza virus infections in macaques. J. Infect. Dis. 199, 405–413.PubMedCrossRefGoogle Scholar
  16. 16.
    Stittelaar, K.J., Tisdale, M., van Amerongen, G., van Lavieren, R.F., Pistoor,F., Simon, J. and Osterhaus, A.D. (2008) Evaluation of intravenous zanamivir against experimental influenza A (H5N1) virus infection in cynomolgus macaques. Antiviral Res. 80, 225–228.PubMedCrossRefGoogle Scholar
  17. 17.
    Kuiken, T., Rimmelzwaan, G.F., Van Amerongen, G. and Osterhaus A.D. (2003) Pathology of human influenza A (H5N1) virus infection in cynomolgus macaques (Macaca fascicularis). Vet. Pathol. 40, 304–310.PubMedCrossRefGoogle Scholar
  18. 18.
    Rimmelzwaan, G.F., Kuiken, T., van Amerongen, G., Bestebroer, T.M., Fouchier, R.A. and Osterhaus A.D. (2001) Pathogenesis of influenza A (H5N1) virus infection in a primate model. J. Virol. 75, 6687–6691.PubMedCrossRefGoogle Scholar
  19. 19.
    Rimmelzwaan, G.F., Baars, M., van Amerongen, G., van Beek, R. and Osterhaus, A.D. (2001) A single dose of an ISCOM influenza vaccine induces long-lasting protective immunity against homologous challenge infection but fails to protect Cynomolgus macaques against distant drift variants of influenza A (H3N2) viruses. Vaccine 20, 158–163.PubMedCrossRefGoogle Scholar
  20. 20.
    Rimmelzwaan, G.F., Baars, M., van Beek, R., van Amerongen, G., Lövgren-Bengtsson, K., Claas, E.C. and Osterhaus, A.D. (1997) Induction of protective immunity against influenza virus in a macaque model: comparison of conventional and iscom vaccines. J. Gen. Virol. 78, 757–765.PubMedGoogle Scholar
  21. 21.
    Lowen, A.C., Mubareka, S., Tumpey, T.M., García-Sastre, A. and Palese P. (2006) The guinea pig as a transmission model for human influenza viruses. Proc. Natl. Acad. Sci. USA 103, 9988–9992.PubMedCrossRefGoogle Scholar
  22. 22.
    Kwon, Y.K., Lipatov, A.S. and Swayne, D.E. (2009) Bronchointerstitial pneumonia in guinea pigs following inoculation with H5N1 high pathogenicity avian influenza virus. Vet. Pathol. 46, 138–141.PubMedCrossRefGoogle Scholar
  23. 23.
    Tang, X. and Chong, K.T. (2009) Histopathology and growth kinetics of influenza viruses (H1N1 and H3N2) in the upper and lower airways. J. Gen. Virol. 90, 386–391.PubMedCrossRefGoogle Scholar
  24. 24.
    Mubareka, S., Lowen, A.C., Steel, J., Coates, A.L., García-Sastre, A. and Palese, P. (2009) Transmission of influenza virus via aerosols and fomites in the guinea pig model. J. Infect. Dis. 199, 858–865.PubMedCrossRefGoogle Scholar
  25. 25.
    Lowen, A.C., Steel, J., Mubareka, S., Carnero, E., García-Sastre, A. and Palese, P. (2009) Blocking interhost transmission of influenza virus by vaccination in the guinea pig model. J. Virol. 83, 2803–2818.PubMedCrossRefGoogle Scholar
  26. 26.
    Van Hoeven, N., Belser, J.A., Szretter, K.J., Zeng, H., Staeheli, P., Swayne, D.E., Katz, J.M. and Tumpey, T.M. (2009) Pathogenesis of 1918 pandemic and H5N1 influenza virus infections in a guinea pig model: antiviral potential of exogenous alpha interferon to reduce virus shedding. J Virol. 83, 2851–2861.PubMedCrossRefGoogle Scholar
  27. 27.
    Steel, J., Lowen, A.C., Mubareka, S. and Palese, P. (2009) Transmission of influenza virus in a mammalian host is increased by PB2 amino acids 627K or 627E/701N. PLoS Pathog. 5, e1000252.PubMedCrossRefGoogle Scholar
  28. 28.
    Lowen, A.C., Mubareka, S., Steel, J. and Palese, P. (2007) Influenza virus transmission is dependent on relative humidity and temperature. PLoS Pathog. 3, 1470–1476.PubMedCrossRefGoogle Scholar
  29. 29.
    Ottolini, M.G., Blanco, J.C., Eichelberger, M.C., Porter, D.D., Pletneva, L., Richardson, J.Y. and Prince, G.A. (2005) The cotton rat provides a useful small-animal model for the study of influenza virus pathogenesis. J. Gen. Virol. 86, 2823–2830.PubMedCrossRefGoogle Scholar
  30. 30.
    Itoh, Y., Shinya, K., Kiso, M., Watanabe, T., Sakoda, Y., Hatta, M., Muramoto, Y., Tamura, D., Sakai-Tagawa, Y., Noda, T., Sakabe, S., Imai, M., Hatta, Y., Watanabe, S., Li, C., Yamada, S., Fujii, K., Murakami, S., Imai, H., Kakugawa, S., Ito, M., Takano, R., Iwatsuki-Horimoto, K., Shimojima, M., Horimoto, T., Goto, H., Takahashi, K., Makino, A., Ishigaki, H., Nakayama, M., Okamatsu, M., Takahashi, K., Warshauer, D., Shult, P.A., Saito, R., Suzuki, H., Furuta, Y., Yamashita, M., Mitamura, K., Nakano, K., Nakamura, M., Brockman-Schneider, R., Mitamura, H., Yamazaki, M., Sugaya, N., Suresh, M., Ozawa, M., Neumann, G., Gern, J., Kida, H., Ogasawara, K. and Kawaoka, Y. (2009) In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature 460, 1021–1025.PubMedGoogle Scholar
  31. 31.
    Lange, E., Kalthoff, D., Blohm, U., Teifke, J.P., Breithaupt, A., Maresch, C., Starick, E., Fereidouni, S., Hoffmann, B., Mettenleiter, T.C., Beer, M. and Vahlenkamp, T.W. (2009) Pathogenesis and transmission of the novel swine-origin influenza virus A/H1N1 after experimental infection of pigs. J. Gen. Virol. 90, 2119–2123.PubMedCrossRefGoogle Scholar
  32. 32.
    Lipatov, A.S., Kwon, Y.K., Sarmento, L.V., Lager, K.M., Spackman, E., Suarez, D.L. and Swayne, D.E. (2008) Domestic pigs have low susceptibility to H5N1 highly pathogenic avian influenza viruses. PLoS Pathog. 4, e1000102.PubMedCrossRefGoogle Scholar
  33. 33.
    Seo, S.H., Webby, R. and Webster, R.G. (2004) No apoptotic deaths and different levels of inductions of inflammatory cytokines in alveolar macrophages infected with influenza viruses. Virology 329, 270–279.PubMedGoogle Scholar
  34. 34.
    Murphy, B.R., Park, E.J., Gottlieb, P. and Subbarao, K. (1997) An influenza A live attenuated reassortant virus possessing three temperature-sensitive mutations in the PB2 polymerase gene rapidly loses temperature sensitivity following replication in hamsters. Vaccine 15, 1372–1378.PubMedCrossRefGoogle Scholar
  35. 35.
    Kuiken, T., Rimmelzwaan, G., van Riel, D., van Amerongen, G., Baars, M., Fouchier, R. and Osterhaus, A. (2004) Avian H5N1 influenza in cats. Science 306, 241.PubMedCrossRefGoogle Scholar
  36. 36.
    Rimmelzwaan, G.F., van Riel, D., Baars, M., Bestebroer, T.M., van Amerongen, G., Fouchier, R.A., Osterhaus, A.D. and Kuiken, T. (2006) Influenza A virus (H5N1) infection in cats causes systemic disease with potential novel routes of virus spread within and between hosts. Am. J. Pathol. 168, 176–183.PubMedCrossRefGoogle Scholar
  37. 37.
    Munster, V.J., Schrauwen, E.J., de Wit, E., van den Brand, J.M., Bestebroer, T.M., Herfst, S., Rimmelzwaan, G.F., Osterhaus, A.D. and Fouchier, R.A. (2010) Insertion of a multi basic cleavage motif into the hemagglutinin of a low pathogenic avian influenza H6N1 virus induces a highly pathogenic phenotype. J. Virol. 84, 7953–7960.Google Scholar
  38. 38.
    Rimmelzwaan, G.F., Claas, E.C., van Amerongen, G., de Jong, J.C. and Osterhaus, A.D. (1999) ISCOM vaccine induced protection against a lethal challenge with a human H5N1 influenza virus. Vaccine 17, 1355–1358.PubMedCrossRefGoogle Scholar
  39. 39.
    Latorre-Margalef, N., Gunnarsson, G., Munster, V.J., Fouchier, R.A., Osterhaus, A.D., Elmberg, J., Olsen, B., Wallensten, A., Haemig, P.D., Fransson, T., Brudin, L. and Waldenström, J. (2009) Effects of influenza A virus infection on migrating mallard ducks. Proc. Biol. Sci. 276, 1029–1036.PubMedCrossRefGoogle Scholar
  40. 40.
    Keawcharoen, J., van Riel, D., van Amerongen, G., Bestebroer, T., Beyer, W.E., van Lavieren, R., Osterhaus, A.D., Fouchier, R.A. and Kuiken, T. (2008) Wild ducks as long-distance vectors of highly pathogenic avian influenza virus (H5N1). Emerg. Infect. Dis. 14, 600–607.PubMedCrossRefGoogle Scholar
  41. 41.
    Rowe, T., León, A.J., Crevar, C.J., Carter, D.M., Xu, L., Ran, L., Fang,Y., Cameron, C.M., Cameron, M,J., Banner, D., Ng, D.C., Ran, R., Weirback, H.K., Wiley, C.A., Kelvin, D.J. and Ross, T.M. (2010) Modeling host responses in ferrets during A/California/07/2009 influenza infection. Virology 401, 257–265.Google Scholar
  42. 42.
    Seo, S.H., Peiris, M. and Webster, R.G. (2002) Protective cross-reactive cellular immunity to lethal A/Goose/Guangdong/1/96-like H5N1 influenza virus is correlated with the proportion of pulmonary CD8(+) T cells expressing gamma interferon. J. Virol. 76, 4886–4890.PubMedCrossRefGoogle Scholar
  43. 43.
    Rimmelzwaan, G.F., Baars, M., Claas, E.C. and Osterhaus, A.D. (1998) Comparison of RNA hybridization, hemagglutination assay, titration of infectious virus and immunofluorescence as methods for monitoring influenza virus replication in vitro. J. Virol. Methods 74, 57–66.PubMedCrossRefGoogle Scholar
  44. 44.
    Karber, G. (1931) Beitrag zur kollektiven behandlung pharmakologischer reihenversuche. Exp. Pathol. Pharmakol. 162, 480–483.CrossRefGoogle Scholar
  45. 45.
    Reed, L.J. and Muench, H. (1938) A simple method for estimating fifty percent endpoints. Am. J. Hyg. 27, 493–497.Google Scholar
  46. 46.
    de Wit, E., Spronken, M.I., Bestebroer, T.M., Rimmelzwaan, G.F., Osterhaus, A.D. and Fouchier, R.A. (2004) Efficient generation and growth of influenza virus A/PR/8/34 from eight cDNA fragments. Virus Res. 103, 155–161.PubMedCrossRefGoogle Scholar
  47. 47.
    Herfst, S., van den Brand, J.M., Schrauwen, E.J.M., de Wit, E., Munster, V.J., van Amerongen, A., Linster, M., Zaaraoui, F., van IJken, W.F.J., Rimmelzwaan, G.F., Osterhaus A.D.M.E., Fouchier, R.A.M., Andeweg, A.C. and Kuiken, T. (2010) Pandemic 2009 H1N1 influenza virus causes diffuse alveolar damage in cynomolgus macaques. Vet. Pathol. 47, 1040–1047.Google Scholar
  48. 48.
    Porter, H.G., Porter, D.D. and Larsen, A.E. (1982) Aleutian disease in ferrets. Infect. Immun. 36, 379–386.PubMedGoogle Scholar
  49. 49.
    Philippa, J., Baas, C., Beyer, W., Bestebroer, T., Fouchier, R., Smith, D., Schaftenaar, W. and Osterhaus, A. (2007) Vaccination against highly pathogenic avian influenza H5N1 virus in zoos using an adjuvanted inactivated H5N2 vaccine. Vaccine 25, 3800–3008.PubMedCrossRefGoogle Scholar
  50. 50.
    Kuiken, T., van den Brand, J., Pantin-Jackwood, M. and Swayne, D.E. (2010) Comparative Pathology of Select Agent Influenza A Virus Infections. Vet. Pathol. 47, 893–914.Google Scholar
  51. 51.
    Bodewes, R., Rimmelzwaan, G.F. and Osterhaus A.D. (2010) Animal models for the preclinical evaluation of candidate influenza vaccines. Expert Rev. Vaccines 9, 59–72.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Edwin J. B. Veldhuis Kroeze
    • 1
  • Thijs Kuiken
    • 1
  • Albert D. M. E. Osterhaus
    • 1
  1. 1.Department of VirologyErasmus Medical CenterRotterdamThe Netherlands

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