Archives of Virology

, Volume 154, Issue 8, pp 1241–1248

Replication and pathogenesis associated with H5N1, H5N2, and H5N3 low-pathogenic avian influenza virus infection in chickens and ducks

  • Egbert Mundt
  • Lauren Gay
  • Les Jones
  • Geraldine Saavedra
  • S. Mark Tompkins
  • Ralph A. Tripp
Original Article


A comparative study examining replication and disease pathogenesis associated with low-pathogenic H5N1, H5N2, or H5N3 avian influenza virus (AIV) infection of chickens and ducks was performed. The replication and pathogenesis of highly pathogenic AIV (HPAIV) has received substantial attention; however, the behavior of low-pathogenic AIVs, which serve as precursors to HPAIVs, has received less attention. Thus, chickens or ducks were inoculated with an isolate from a wild bird [A/Mute Swan/MI/451072/06 (H5N1)] or isolates from chickens [A/Ck/PA/13609/93 (H5N2), A/Ck/TX/167280-4/02 (H5N3)], and virus replication, induction of a serological response, and disease pathogenesis were investigated, and the hemagglutinin and neuraminidase (NA) gene sequences of the isolates were determined. Virus isolated from tracheal and cloacal swabs showed that H5N1 replicated better in ducks, whereas H5N2 and H5N3 replicated better in chickens. Comparison of the NA gene sequences showed that chicken-adapted H5N2 and H5N3 isolates both have a deletion of 20 amino acids in the NA stalk region, which was absent in the H5N1 isolate. Histopathological examination of numerous organs showed that H5N2 and H5N3 isolates caused lesions in chickens in a variety of organs, but to a greater extent in the respiratory and intestinal tracts, whereas H5N1 lesions in ducks were observed mainly in the respiratory tract. This study suggests that the H5N1, H5N2, and H5N3 infections occurred at distinct sites in chicken and ducks, and that comparative studies in different model species are needed to better understand the factors influencing the evolution of these viruses.


  1. 1.
    Alexander DJ (2000) A review of avian influenza in different bird species. Vet Microbiol 74:3–13PubMedCrossRefGoogle Scholar
  2. 2.
    Banks J, Speidel ES, Moore E, Plowright L, Piccirillo A, Capua I, Cordioli P, Fioretti A, Alexander DJ (2001) Changes in the haemagglutinin and the neuraminidase genes prior to the emergence of highly pathogenic H7N1 avian influenza viruses in Italy. Arch Virol 146:963–973PubMedCrossRefGoogle Scholar
  3. 3.
    Baigent SJ, McCauley JW (2001) Glycosylation of haemagglutinin and stalk-length of neuraminidase combine to regulate the growth of avian influenza viruses in tissue culture. Virus Res 79:177–185PubMedCrossRefGoogle Scholar
  4. 4.
    Beigel JH, Farrar J, Han AM, Hayden FG, Hyer R (2005) Avian influenza (H5N1) infections in humans. N Engl J Med 353:1374–1385PubMedCrossRefGoogle Scholar
  5. 5.
    Bosch FX, Orlich M, Klenk H-D, Rott R (1979) The structure of the hemagglutinin, a determinant for the pathogenicity of influenza viruses. Virology 95:197–207PubMedCrossRefGoogle Scholar
  6. 6.
    Boycott R, Klenk H-D, Ohuchi M (1994) Cell tropism of influenza virus mediated by hemagglutinin activation at the stage of virus entry. Virology 203:313–319PubMedCrossRefGoogle Scholar
  7. 7.
    Brown JD, Stallknecht DE, Beck JR, Suarez DL, Swayne DE (2006) Susceptibility of North American ducks and gulls to H5N1 highly pathogenic avian influenza viruses. Emerg Infect Dis 12:1663–1670PubMedGoogle Scholar
  8. 8.
    Campitelli L, Mogavero E, De Marco MA, Delogu M, Puzelli S, Frezza F, Facchini M, Chiapponi C, Foni E, Cordioli P, Webby R, Barigazzi G, Webster RG, Donatelli I (2004) Interspecies transmission of an H7N3 influenza virus from wild birds to intensively reared domestic poultry in Italy. Virology 323:24–36PubMedCrossRefGoogle 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.
    Hinshaw VS, Air GM, Gibbs AJ, Graves L, Prescott B, Karunakaran D (1982) Antigenic and genetic characterization of a novel hemagglutinin subtype of influenza A viruses from gulls. J Virol 42:865–872PubMedGoogle Scholar
  11. 11.
    Horimoto T, Kawaoka Y (1994) Reverse genetics provides direct evidence for a correlation of hemagglutinin cleavability and virulence of an avian influenza A virus. J Virol 68:3120–3128PubMedGoogle Scholar
  12. 12.
    Kawaoka Y, Yamnikova S, Chambers TM, Lvov DK, Webster RG (1990) Molecular characterization of a new hemagglutinin, subtype H14, of influenza A virus. Virology 179:759–767PubMedCrossRefGoogle Scholar
  13. 13.
    Lee CW, Senne DA, Linares JA, Woolcock PR, Stallknecht DE, Spackman E, Swayne DE, Suarez DL (2004) Characterization of recent H5 subtype avian influenza viruses from US poultry. Avian Pathol 33:288–297PubMedCrossRefGoogle Scholar
  14. 14.
    Lee CW, Suarez DL, Tumpey TM, Sung HW, Kwon YK, Lee YJ, Choi JG, Joh SJ, Kim MC, Lee EK, Park JM, Lu X, Katz JM, Spacemen E, Swayne DE, Kim JH (2005) Characterization of highly pathogenic H5N1 avian influenza A viruses isolated from South Korea. J Virol 79:3692–3702PubMedCrossRefGoogle Scholar
  15. 15.
    Lee CW, Swayne DE, Linares JA, Senne DA, Suarez DL (2005) H5N2 avian influenza outbreak in Texas in 2004: the first highly pathogenic strain in the United States in 20 years? J Virol 79:11412–11421PubMedCrossRefGoogle Scholar
  16. 16.
    Lewis DB (2006) Avian to human influenza. Annu Rev Med 57:139–154PubMedCrossRefGoogle Scholar
  17. 17.
    Li SQ, Orlich M, Rott R (1990) Generation of seal influenza virus variants pathogenic for chickens, because of hemagglutinin cleavage site changes. J Virol 64:3297–3303PubMedGoogle Scholar
  18. 18.
    Matrosovich M, Zhou N, Kawaoka Y, Webster R (1999) The surface glycoproteins of H5 influenza viruses from humans, chickens, and wild aquatic birds have distinguishable properties. J Virol 73:1146–1155PubMedGoogle Scholar
  19. 19.
    OIE (2006) Manual of diagnostic tests and vaccines for terrestrial animals.
  20. 20.
    Pillai SP, Suarez DL, Pantin-Jackwood M, Lee CW (2008) Pathogenicity and transmission studies of H5N2 parrot avian influenza virus of Mexican lineage in different poultry species. Vet Microbiol 129:48–57PubMedCrossRefGoogle Scholar
  21. 21.
    Reed LJ, Muench H (1938) A simple method of estimating fifty per cent endpoints. Am J Hyg 27:493–497Google Scholar
  22. 22.
    Rohm C, Zhou N, Suss J, Mackenzie J, Webster RG (1996) Characterization of a novel influenza hemagglutinin, H15: criteria for determination of influenza A subtypes. Virology 217:508–516PubMedCrossRefGoogle Scholar
  23. 23.
    Slemons RD, Johnson DC, Osborn JS, Hayes F (1974) Type-A influenza viruses isolated from wild free-flying ducks in California. Avian Dis 18:119–124PubMedCrossRefGoogle Scholar
  24. 24.
    Spackman E, Swayne DE, Suarez DL, Senne DA, Pedersen JC, Killian ML, Pasick J, Handel K, Pillai SP, Lee CW, Stallknecht D, Slemons R, Ip HS, Deliberto T (2007) Characterization of low-pathogenicity H5N1 avian influenza viruses from North America. J Virol 81:11612–11619PubMedCrossRefGoogle Scholar
  25. 25.
    Stallknecht DE, Shane SM (1988) Host range of avian influenza virus in free-living birds. Vet Res Commun 12:125–141PubMedCrossRefGoogle Scholar
  26. 26.
    Sturm-Ramirez KM, Hulse-Post DJ, Govorkova EA, Humberd J, Seiler P, Puthavathana P, Buranathai C, Nguyen TD, Chaisingh A, Long HT, Naipospos TS, Chen H, Ellis TM, Guan Y, Peiris JS, Webster RG (2005) Are ducks contributing to the endemicity of highly pathogenic H5N1 influenza virus in Asia? J Virol 79:11269–11279PubMedCrossRefGoogle Scholar
  27. 27.
    Webster RG, Bean WJ, Gorman OT, Chambers TM, Kawaoka Y (1992) Evolution and ecology of influenza A viruses. Microbiol Rev 56:152–179PubMedGoogle Scholar
  28. 28.
    Webster RG, Rott R (1987) Influenza virus A pathogenicity: the pivotal role of hemagglutinin. Cell 50:665–666PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Egbert Mundt
    • 1
  • Lauren Gay
    • 1
  • Les Jones
    • 2
  • Geraldine Saavedra
    • 2
  • S. Mark Tompkins
    • 2
  • Ralph A. Tripp
    • 2
  1. 1.Department of Population Health, Poultry Diagnostic and Research Center, College of Veterinary MedicineUniversity of GeorgiaAthensUSA
  2. 2.Department of Infectious Diseases, College of Veterinary MedicineUniversity of GeorgiaAthensUSA

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