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Archives of Virology

, Volume 156, Issue 5, pp 759–767 | Cite as

Pandemic H1N1 influenza virus causes a stronger inflammatory response than seasonal H1N1 influenza virus in ferrets

  • Young Myong Kang
  • Byung Min Song
  • Joo Sub Lee
  • Hyun Soo Kim
  • Sang Heui SeoEmail author
Original Article

Abstract

A 2009 H1N1 influenza virus pandemic, which had its origin in swine, caused severe illness and mortality in humans. Inflammatory responses may be responsible for pathogenesis caused by infection with influenza viruses. To better understand the pathogenic mechanism, clinical signs and inflammatory responses in ferrets infected with the pandemic H1N1 were compared with those caused by seasonal H1N1 influenza virus. Ferrets infected with the 2009 pandemic H1N1 virus displayed higher body temperatures, greater reduction in body weight, and higher viral titers in the tracheae and lungs. Levels of inflammatory cytokines, including interleukin-6, interferon-alpha, and tumor necrosis factor-alpha, were higher in the lungs of ferrets infected with the 2009 pandemic H1N1. The data support the idea that increased pathogenesis caused by the 2009 pandemic H1N1 influenza virus may have been partially mediated by a higher induction of pro-inflammatory cytokines in the lungs of affected humans or animals.

Keywords

Influenza Virus Avian Influenza Virus H1N1 Influenza Virus Pandemic H1N1 Swine Influenza Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This study was supported in part by a grant (A084411) from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea. We wish to thank HARRISCO, an English editing company, for help editing the manuscript.

References

  1. 1.
    Armstrong SJ, Dimmock NJ (1992) Neutralization of influenza virus by low concentrations of hemagglutinin-specific polymeric immunoglobulin A inhibits viral fusion activity, but activation of the ribonucleoprotein is also inhibited. J Virol 66:3823–3832PubMedGoogle Scholar
  2. 2.
    Bancrof JD, Stevens A (1996) Theory and practice of histological techniques, 4th edn. Churchill Livingstone, New YorkGoogle Scholar
  3. 3.
    Basler CF, Reid AH, Dybing JK, Janczewski TA, Fanning TG, Zheng H, Salvatore M, Perdue ML, Swayne DE, García-Sastre A, Palese P, Taubenberger JK (2001) Sequence of the 1918 pandemic influenza virus nonstructural gene (NS) segment and characterization of recombinant viruses bearing the 1918 NS genes. Proc Natl Acad Sci USA 98:2746–2751PubMedCrossRefGoogle Scholar
  4. 4.
    Centers for Disease Control and Prevention (CDC) (2009) Outbreak of swine-origin influenza A (H1N1) virus infection-Mexico, March–April 2009. MMWR Morb Mortal Wkly Rep 58:467–470Google Scholar
  5. 5.
    Chang LY, Shih SR, Shao PL, Huang DT, Huang LM (2009) Novel swine-origin influenza virus A (H1N1): the first pandemic of the 21st century. J Formos Med Assoc 108:526–532PubMedCrossRefGoogle Scholar
  6. 6.
    Cheung CY, Poon LL, Lau AS, Luk W, Lau YL, Shortridge KF, Gordon S, Guan Y, Peiris JS (2002) Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease? Lancet 360:1831–1837PubMedCrossRefGoogle Scholar
  7. 7.
    de Jong MD, Simmons CP, Thanh TT, Hien VM, Smith GJ, Chau TN, Hoang DM, Chau NV, Khanh TH, Dong VC, Qui PT, Cam BV, Ha do Q, Guan Y, Peiris JS, Chinh NT, Hien TT, Farrar J (2006) Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat Med 12:1203–1207PubMedCrossRefGoogle Scholar
  8. 8.
    Desselberger U, Racaniello VR, Zazra JJ, Palese P (1980) The 3′ and 5′-terminal sequences of influenza A, B and C virus RNA segments are highly conserved and show partial inverted complementarity. Gene 8:315–328PubMedCrossRefGoogle Scholar
  9. 9.
    Fouchier RA, Munster V, Wallensten A, Bestebroer TM, Herfst S, Smith D, Rimmelzwaan GF, Olsen B, Osterhaus AD (2005) Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls. J Virol 79:2814–2822PubMedCrossRefGoogle Scholar
  10. 10.
    Garten RJ, Davis CT, Russell CA, Shu B, Lindstrom S, Balish A, Sessions WM, Xu X, Skepner E, Deyde V, Okomo-Adhiambo M, Gubareva L, Barnes J, Smith CB, Emery SL, Hillman MJ, Rivailler P, Smagala J, de Graaf M, Burke DF, Fouchier RA, Pappas C, Alpuche-Aranda CM, López-Gatell H, Olivera H, López I, Myers CA, Faix D, Blair PJ, Yu C, Keene KM, Dotson PD Jr, Boxrud D, Sambol AR, Abid SH, St George K, Bannerman T, Moore AL, Stringer DJ, Blevins P, Demmler-Harrison GJ, Ginsberg M, Kriner P, Waterman S, Smole S, Guevara HF, Belongia EA, Clark PA, Beatrice ST, Donis R, Katz J, Finelli L, Bridges CB, Shaw M, Jernigan DB, Uyeki TM, Smith DJ, Klimov AI, Cox NJ (2009) Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science 325:197–201PubMedCrossRefGoogle Scholar
  11. 11.
    Hamelin ME, Baz M, Abed Y, Couture C, Joubert P, Beaulieu E, Bellerose N, Plante M, Mallett C, Schumer G, Kobinger GP, Boivin G (2010) Oseltamivir-resistant pandemic A/H1N1 virus is as virulent as its wild-type counterpart in mice and ferrets. PLoS Pathog 6:e1001015Google Scholar
  12. 12.
  13. 13.
  14. 14.
  15. 15.
    Hwang SD, Shin JS, Ku KB, Kim HS, Cho SW, Seo SH (2010) Protection of pregnant mice, fetuses and neonates from lethality of H5N1 influenza viruses by maternal vaccination. Vaccine 28:2957–2964PubMedCrossRefGoogle Scholar
  16. 16.
    Ilyushina NA, Seiler JP, Rehg JE, Webster RG, Govorkova EA (2010) Effect of neuraminidase inhibitor-resistant mutations on pathogenicity of clade 2.2 A/Turkey/15/06 (H5N1) influenza virus in ferrets. PLoS Pathog 6:e1000933Google Scholar
  17. 17.
    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 PA, 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, Kawaoka Y (2009) In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature 460:1021–1025PubMedGoogle Scholar
  18. 18.
    Kawaoka Y, Krauss S, Webster RG (1993) Avian-to-human transmission of the PB1 gene of influenza A viruses in the 1957 and 1968 pandemics. Virology 194:781–788PubMedCrossRefGoogle Scholar
  19. 19.
    Kim HM, Lee YW, Lee KJ, Kim HS, Cho SW, van Rooijen N, Guan Y, Seo SH (2008) Alveolar macrophages are indispensable for controlling influenza viruses in lungs of pigs. J Virol 82:4265–4274PubMedCrossRefGoogle Scholar
  20. 20.
    Kim YH, Kim HS, Cho SH, Seo SH (2009) Influenza B virus causes milder pathogenesis and weaker inflammatory responses in ferrets than influenza A virus. Viral Immunol 22:423–430PubMedCrossRefGoogle Scholar
  21. 21.
    Kobasa D, Jones SM, Shinya K, Kash JC, Copps J, Ebihara H, Hatta Y, Kim JH, Halfmann P, Hatta M, Feldmann F, Alimonti JB, Fernando L, Li Y, Katze MG, Feldmann H, Kawaoka Y (2007) Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus. Nature 445:319–323PubMedCrossRefGoogle Scholar
  22. 22.
    Kwon D, Shin K, Kim S, Ha Y, Choi JH, Yang JS, Lee JY, Chae C, Oh HB, Kang C (2010) Replication and pathogenesis of the pandemic (H1N1) 2009 influenza virus in mammalian models. J Microbiol 48:657–662PubMedCrossRefGoogle Scholar
  23. 23.
    Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408PubMedCrossRefGoogle Scholar
  24. 24.
    McGeoch D, Fellner P, Newton C (1976) Influenza virus genome consists of eight distinct RNA species. Proc Natl Acad Sci USA 73:3045–3049PubMedCrossRefGoogle Scholar
  25. 25.
    Munster VJ, de Wit E, van den Brand JM, Herfst S, Schrauwen EJ, Bestebroer TM, van de Vijver D, Boucher CA, Koopmans M, Rimmelzwaan GF, Kuiken T, Osterhaus AD, Fouchier RA (2009) Pathogenesis and transmission of swine-origin 2009 A(H1N1) influenza virus in ferrets. Science 325:481–483PubMedGoogle Scholar
  26. 26.
    Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team, Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, Garten RJ, Gubareva LV, Xu X, Bridges CB, Uyeki TM (2009) Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 360:2605–2615Google Scholar
  27. 27.
    Perrone LA, Plowden JK, García-Sastre A, Katz JM, Tumpey TM (2008) H5N1 and 1918 pandemic influenza virus infection results in early and excessive infiltration of macrophages and neutrophils in the lungs of mice. PLoS Pathog 4:e1000115Google Scholar
  28. 28.
    Pushko P, Kort T, Nathan M, Pearce MB, Smith G, Tumpey TM (2010) Recombinant H1N1 virus-like particle vaccine elicits protective immunity in ferrets against the 2009 pandemic H1N1 influenza virus. Vaccine 28:4771–4776PubMedCrossRefGoogle Scholar
  29. 29.
    Reed LE, Muench H (1938) A simple method for estimating fifty percent endpoints. Am J Hyg 27:493–497Google Scholar
  30. 30.
    Reid AH, Fanning TG, Hultin JV, Taubenberger JK (1999) Origin and evolution of the 1918 “Spanish” influenza virus hemagglutinin gene. Proc Natl Acad Sci USA 96:1651–1656PubMedCrossRefGoogle Scholar
  31. 31.
    Reid AH, Fanning TG, Janczewski TA, Taubenberger JK (2000) Characterization of the 1918 “Spanish” influenza virus neuraminidase gene. Proc Natl Acad Sci USA 97:6785–6790PubMedCrossRefGoogle Scholar
  32. 32.
    Reid AH, Taubenberger JK, Fanning TG (2001) The 1918 Spanish influenza: integrating history and biology. Microbes Infect 3:81–87PubMedCrossRefGoogle Scholar
  33. 33.
    Rogers GN, Paulson JC (1983) Receptor determinants of human and animal influenza virus isolates: differences in receptor specificity of the H3 hemagglutinin based on species of origin. Virology 127:361–373PubMedCrossRefGoogle Scholar
  34. 34.
    Schäfer JR, Kawaoka Y, Bean WJ, Süss J, Senne D, Webster RG (1993) Origin of the pandemic 1957 H2 influenza A virus and the persistence of its possible progenitors in the avian reservoir. Virology 194:781–788PubMedCrossRefGoogle Scholar
  35. 35.
    Seo SH, Webby R, Webster RG (2004) No apoptotic deaths and different levels of inductions of inflammatory cytokines in alveolar macrophages infected with influenza viruses. Virology 329:270–279PubMedGoogle Scholar
  36. 36.
    Shin JS, Kim HS, Cho SH, Seo SH (2010) IgG antibodies mediate protective immunity of inactivated vaccine for highly pathogenic H5N1 influenza viruses in ferrets. Viral Immunol 23:321–327PubMedCrossRefGoogle Scholar
  37. 37.
    Shin JS, Hwang SD, Kim HS, Cho SW, Seo SH (2010) Protection of ferrets from infection by swine-origin 2009 A (H1N1) influenza virus by the inactivated vaccine. Viral Immunol 23:395–402PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Young Myong Kang
    • 1
    • 2
  • Byung Min Song
    • 1
    • 2
  • Joo Sub Lee
    • 1
    • 2
  • Hyun Soo Kim
    • 3
  • Sang Heui Seo
    • 1
    • 2
    Email author
  1. 1.Laboratory of Influenza Research, College of Veterinary MedicineChungnam National UniversityDaejeonKorea
  2. 2.Institute of Influenza Research, College of Veterinary MedicineChungnam National UniversityDaejeonKorea
  3. 3.Laboratory of Public Health, College of Veterinary MedicineChungnam National UniversityDaejeonKorea

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