Zoonotic Influenza and Human Health—Part 1: Virology and Epidemiology of Zoonotic Influenzas

  • L. W. Goneau
  • K. Mehta
  • J. Wong
  • A. G. L’Huillier
  • J. B. GubbayEmail author
Tropical, Travel and Emerging Infections (L Chen and A Boggild, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Tropical, Travel and Emerging Infections


Purpose of Review

Zoonotic influenza viruses are those that cross the animal-human barrier and can cause disease in humans, manifesting from minor respiratory illnesses to multiorgan dysfunction. They have also been implicated in the causation of deadly pandemics in recent history. The increasing incidence of infections caused by these viruses worldwide has necessitated focused attention to improve both diagnostic as well as treatment modalities. In this first part of a two-part review, we describe the structure of zoonotic influenza viruses, the relationship between mutation and pandemic capacity, pathogenesis of infection, and also discuss history and epidemiology.

Recent Findings

We are currently witnessing the fifth and the largest wave of the avian influenza A(H7N9) epidemic. Also in circulation are a number of other zoonotic influenza viruses, including avian influenza A(H5N1) and A(H5N6); avian influenza A(H7N2); and swine influenza A(H1N1)v, A(H1N2)v, and A(H3N2)v viruses. Most recently, the first human case of avian influenza A(H7N4) infection has been documented.


By understanding the virology and epidemiology of emerging zoonotic influenzas, we are better prepared to face a new pandemic. However, continued effort is warranted to build on this knowledge in order to efficiently combat the constant threat posed by the zoonotic influenza viruses.


Zoonotic influenza Avian influenza Swine influenza Pandemic 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Prescott J. Man and microbes. Disease and plagues in history and modern times. Can Vet J. 1996;37(7):425.PubMedCentralGoogle Scholar
  2. 2.
    Winter AL, Eshaghi A, Farrell DJ, King A, Li A, Li Y, et al. Variant influenza A (H1N1) virus infection in Canada. J Clin Virol. 2013;57(3):279–81. Scholar
  3. 3.
    •• World Health Organization. Human cases of influenza at the human-animal interface, January 2015 – April 2017. Wkly Epidemiol Rec. 2017;92(33):460–75. Available at Accessed December 13, 2017. This reference enlists the total number of recorded cases of human cases of influenza at the human-animal interface.
  4. 4.
    Gething MJ, Bye J, Skehel J, Waterfield M. Cloning and DNA sequence of double-stranded copies of haemagglutinin genes from H2 and H3 strains elucidates antigenic shift and drift in human influenza virus. Nature. 1980;287(5780):301–6. Accessed December 10, 2017PubMedCrossRefGoogle Scholar
  5. 5.
    •• Centers for Disease Control and Prevention. Past pandemics. Available at Accessed 2 December 2017. This reference provides useful information regarding previously documented pandemic influenzas.
  6. 6.
    Ducatez MF, Pelletier C, Meyer G. Influenza D virus in cattle, France, 2011–2014. Emerg Infect Dis. 2015;21(2):368–71. Scholar
  7. 7.
    Beare AS, Webster RG. Replication of avian influenza viruses in humans. Arch Virol. 1991;119(1–2):37–42. Scholar
  8. 8.
    Hoelzer K, Murcia PR, Baillie GJ, Wood JLN, Metzger SM, Osterrieder N, et al. Intrahost evolutionary dynamics of canine influenza virus in naive and partially immune dogs. J Virol. 2010;84(10):5329–35. Scholar
  9. 9.
    Murcia PR, Hughes J, Battista P, et al. Evolution of an Eurasian avian-like influenza virus in naïve and vaccinated pigs. Wilke CO, ed. PLoS Pathog. 2012;8(5):e1002730. doi:
  10. 10.
    • Munoz O, De Nardi M, Van Der Meulen K, et al. Genetic adaptation of influenza a viruses in domestic animals and their potential role in interspecies transmission: a literature review. EcoHealth. 2016;13(1):171–98. This reference describes the genetic adaptation of influenza A viruses in domestic animals and their potential role in interspecies transmission.
  11. 11.
    Jonges M, Bataille A, Enserink R, Meijer A, Fouchier RAM, Stegeman A, et al. Comparative analysis of avian influenza virus diversity in poultry and humans during a highly pathogenic avian influenza A (H7N7) virus outbreak. J Virol. 2011;85(20):10598–604. Scholar
  12. 12.
    Jonges M, Welkers MR, Jeeninga RE, et al. Emergence of the virulence-associated PB2 E627K substitution in a fatal human case of highly pathogenic avian influenza virus a(H7N7) infection as determined by Illumina ultra-deep sequencing. J Virol. 2014;88(3):1694–702. Scholar
  13. 13.
    Tang JW, Shetty N, Lam TT, Hon KL. Emerging, novel, and known influenza virus infections in humans. Infect Dis Clin N Am. 2010;24(3):603–17. Scholar
  14. 14.
    Villa M, Lässig M. Fitness cost of reassortment in human influenza. Wilke CO, ed. PLoS Pathog. 2017;13(11):e1006685. doi:
  15. 15.
    Gao R, Cao B, Hu Y, Feng Z, Wang D, Hu W, et al. Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med. 2013;368(20):1888–97. Scholar
  16. 16.
    •• Centers for Disease Control and Prevention. Asian Lineage Avian Influenza A (H7N9) Virus. Avian Influenza (Flu). Available at Accessed December 12, 2017. This reference provides useful information regarding H7N9 Influenza A virus.
  17. 17.
    Guan Y, Shortridge KF, Krauss S, Webster RG. Molecular characterization of H9N2 influenza viruses: were they the donors of the “internal” genes of H5N1 viruses in Hong Kong? Proc Natl Acad Sci U S A. 1999;96(16):9363–7. Scholar
  18. 18.
    Lin YP, Shaw M, Gregory V, Cameron K, Lim W, Klimov A, et al. Avian-to-human transmission of H9N2 subtype influenza A viruses: relationship between H9N2 and H5N1 human isolates. Proc Natl Acad Sci. 2000;97(17):9654–8. Scholar
  19. 19.
    Kageyama T, Fujisaki S, Takashita E, Xu H, Yamada S, Uchida Y, et al. Genetic analysis of novel avian a(H7N9) influenza viruses isolated from patients in China, February to April 2013. Euro Surveill. 2013;18(15):20453.PubMedGoogle Scholar
  20. 20.
    Lam TT, Wang J, Shen Y, et al. The genesis and source of the H7N9 influenza viruses causing human infections in China. Nature. 2013;502(7470):241–4. Scholar
  21. 21.
    Wang D, Yang L, Gao R, Zhang X, Tan Y, Wu A, et al. Genetic tuning of the novel avian influenza A(H7N9) virus during interspecies transmission, China, 2013. Eur Secur. 2014;19(25):1–17. Scholar
  22. 22.
    • Pu J, Wang S, Yin Y, Zhang G, Carter RA, Wang J, et al. Evolution of the H9N2 influenza genotype that facilitated the genesis of the novel H7N9 virus. Proc Natl Acad Sci. 2015;112(2):548–53. This reference traces the genesis of the novel H7N9 virus.
  23. 23.
    Xiao C, Ma W, Sun N, Huang L, Li Y, Zeng Z, et al. PB2-588 v promotes the mammalian adaptation of H10N8, H7N9 and H9N2 avian influenza viruses. Sci Rep. 2016;6(1):19474. Scholar
  24. 24.
    Pabbaraju K, Tellier R, Wong S, Li Y, Bastien N, Tang JW, et al. Full-genome analysis of avian influenza A(H5N1) virus from human, North America, 2013. Emerg Infect Dis. 2014;20(5):887–91. Scholar
  25. 25.
    Chen H, Yuan H, Gao R, Zhang J, Wang D, Xiong Y, et al. Clinical and epidemiological characteristics of a fatal case of avian influenza A H10N8 virus infection: a descriptive study. Lancet. 2014;383(9918):714–21. Scholar
  26. 26.
    Thuy DM, Peacock TP, Bich VT, et al. Prevalence and diversity of H9N2 avian influenza in chickens of Northern Vietnam, 2014. Infect Genet Evol. 2016;44:530–40. Scholar
  27. 27.
    Rahimirad S, Alizadeh A, Alizadeh E, Hosseini SM. The avian influenza H9N2 at avian-human interface: a possible risk for the future pandemics. J Res Med Sci. 2016;21(4):51. Scholar
  28. 28.
    Garten RJ, Davis CT, Russell CA, Shu B, Lindstrom S, Balish A, et al. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science. 2009;325(5937):197–201. Scholar
  29. 29.
    Trifonov V, Khiabanian H, Rabadan R. Geographic dependence, surveillance, and origins of the 2009 influenza A (H1N1) virus. N Engl J Med. 2009;361(2):115–9. Scholar
  30. 30.
    Girard MP, Tam JS, Assossou OM, Kieny MP. The 2009 A (H1N1) influenza virus pandemic: a review. Vaccine. 2010;28(31):4895–902. Scholar
  31. 31.
    Connor RJ, Kawaoka Y, Webster RG, Paulson JC. Receptor specificity in human, avian, and equine H2 and H3 influenza virus isolates. Virology. 1994;205(1):17–23. Scholar
  32. 32.
    Matrosovich MN, Gambaryan AS, Teneberg S, Piskarev VE, Yamnikova SS, Lvov DK, et al. Avian influenza A viruses differ from human viruses by recognition of sialyloligosaccharides and gangliosides and by a higher conservation of the HA receptor-binding site. Virology. 1997;233(1):224–34. Scholar
  33. 33.
    Shinya K, Ebina M, Yamada S, Ono M, Kasai N, Kawaoka Y. Influenza virus receptors in the human airway. Nature. 2006;440(7083):435–6. Scholar
  34. 34.
    Costa T, Chaves AJ, Valle R, Darji A, van Riel D, Kuiken T, et al. Distribution patterns of influenza virus receptors and viral attachment patterns in the respiratory and intestinal tracts of seven avian species. Vet Res. 2012;43(1):28. Scholar
  35. 35.
    van Riel D, Munster VJ, de Wit E, Rimmelzwaan GF, Fouchier RAM, Osterhaus ADME, et al. Human and avian influenza viruses target different cells in the lower respiratory tract of humans and other mammals. Am J Pathol. 2007;171(4):1215–23. Scholar
  36. 36.
    Nelli RK, Kuchipudi SV, White GA, Perez BB, Dunham SP, Chang KC. Comparative distribution of human and avian type sialic acid influenza receptors in the pig. BMC Vet Res. 2010;6(1):4. Scholar
  37. 37.
    Van Poucke SG, Nicholls JM, Nauwynck HJ, Van Reeth K. Replication of avian, human and swine influenza viruses in porcine respiratory explants and association with sialic acid distribution. Virol J. 2010;7(1):38. Scholar
  38. 38.
    Kong W, Liu Q, Sun Y, Wang Y, Gao H, Liu L, et al. Transmission and pathogenicity of novel reassortants derived from Eurasian avian-like and 2009 pandemic H1N1 influenza viruses in mice and Guinea pigs. Sci Rep. 2016;6(1):27067. Scholar
  39. 39.
    Wan H, Sorrell EM, Song H, et al. Replication and transmission of H9N2 influenza viruses in ferrets: evaluation of pandemic potential. Baylis M, ed. PLoS One. 2008;3(8):e2923. doi:
  40. 40.
    Li X, Shi J, Guo J, Deng G, Zhang Q, Wang J, et al. Genetics, receptor binding property, and transmissibility in mammals of naturally isolated H9N2 avian influenza viruses. PLoS Pathog. 2014;10(11):e1004508. Scholar
  41. 41.
    Stevens J, Blixt O, Chen LM, Donis RO, Paulson JC, Wilson IA. Recent avian H5N1 viruses exhibit increased propensity for acquiring human receptor specificity. J Mol Biol. 2008;381(5):1382–94. Scholar
  42. 42.
    Xiong X, Xiao H, Martin SR, et al. Enhanced human receptor binding by H5 haemagglutinins. Virology. 2014;456–457(1):179–87. Scholar
  43. 43.
    Belser JA, Blixt O, Chen L-M, Pappas C, Maines TR, van Hoeven N, et al. Contemporary north American influenza H7 viruses possess human receptor specificity: implications for virus transmissibility. Proc Natl Acad Sci U S A. 2008;105(21):7558–63. Scholar
  44. 44.
    de Wit E, Munster VJ, van Riel D, Beyer WEP, Rimmelzwaan GF, Kuiken T, et al. Molecular determinants of adaptation of highly pathogenic avian influenza H7N7 viruses to efficient replication in the human host. J Virol. 2010;84(3):1597–606. Scholar
  45. 45.
    Kilander A, Rykkvin R, Dudman SG, Hungnes O. Observed association between the HA1 mutation D222G in the 2009 pandemic influenza A(H1N1) virus and severe clinical outcome, Norway 2009-2010. Eur Secur. 2010;15(9):6–8.Google Scholar
  46. 46.
    Chutinimitkul S, Herfst S, Steel J, Lowen AC, Ye J, van Riel D, et al. Virulence-associated substitution D222G in the hemagglutinin of 2009 pandemic influenza A(H1N1) virus affects receptor binding. J Virol. 2010;84(22):11802–13. Scholar
  47. 47.
    Ramos I, Krammer F, Hai R, Aguilera D, Bernal-Rubio D, Steel J, et al. H7N9 influenza viruses interact preferentially with α2,3-linked sialic acids and bind weakly to α2,6-linked sialic acids. J Gen Virol. 2013;94(Pt 11):2417–23. Scholar
  48. 48.
    Belser JA, Gustin KM, Pearce MB, Maines TR, Zeng H, Pappas C, et al. Pathogenesis and transmission of avian influenza A (H7N9) virus in ferrets and mice. Nature. 2013;501(7468):556–9. Scholar
  49. 49.
    Xiong X, Martin SR, Haire LF, Wharton SA, Daniels RS, Bennett MS, et al. Receptor binding by an H7N9 influenza virus from humans. Nature. 2013;499(7459):496–9. Scholar
  50. 50.
    Dortmans JC, Dekkers J, Wickramasinghe IN, et al. Adaptation of novel H7N9 influenza A virus to human receptors. Sci Rep. 2013;3(1):3058. Scholar
  51. 51.
    Shi Y, Zhang W, Wang F, Qi J, Wu Y, Song H, et al. Structures and receptor binding of hemagglutinins from human-infecting H7N9 influenza viruses. Science. 2013;342(6155):243–7. Scholar
  52. 52.
    Tharakaraman K, Jayaraman A, Raman R, Viswanathan K, Stebbins NW, Johnson D, et al. Glycan receptor binding of the influenza A virus H7N9 hemagglutinin. Cell. 2013;153(7):1486–93. Scholar
  53. 53.
    Xu R, de Vries RP, Zhu X, Nycholat CM, McBride R, Yu W, et al. Preferential recognition of avian-like receptors in human influenza A H7N9 viruses. Science. 2013;342(6163):1230–5. Scholar
  54. 54.
    Zhou J, Wang D, Gao R, Zhao B, Song J, Qi X, et al. Biological features of novel avian influenza A (H7N9) virus. Nature. 2013;499(7459):500–3. Scholar
  55. 55.
    Wang M, Zhang W, Qi J, Wang F, Zhou J, Bi Y, et al. Structural basis for preferential avian receptor binding by the human-infecting H10N8 avian influenza virus. Nat Commun. 2015;6:5600. Scholar
  56. 56.
    Sun X, Jayaraman A, Maniprasad P, Raman R, Houser KV, Pappas C, et al. N-Linked glycosylation of the hemagglutinin protein influences virulence and antigenicity of the 1918 pandemic and seasonal H1N1 influenza a viruses. J Virol. 2013;87(15):8756–66. Scholar
  57. 57.
    Zhang Y, Zhu J, Li Y, et al. Glycosylation on hemagglutinin affects the virulence and pathogenicity of pandemic H1N1/2009 influenza A virus in mice. Tang JW, ed. PLoS One. 2013;8(4):e61397. doi:
  58. 58.
    Hatta M. Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science. 2001;293(5536):1840–2. Scholar
  59. 59.
    Schrauwen EJA, Herfst S, Leijten LM, van Run P, Bestebroer TM, Linster M, et al. The multibasic cleavage site in H5N1 virus is critical for systemic spread along the olfactory and hematogenous routes in ferrets. J Virol. 2012;86(7):3975–84. Scholar
  60. 60.
    Suguitan AL, Matsuoka Y, Lau Y-F, Santos CP, Vogel L, Cheng LI, et al. The multibasic cleavage site of the hemagglutinin of highly pathogenic a/Vietnam/1203/2004 (H5N1) avian influenza virus acts as a virulence factor in a host-specific manner in mammals. J Virol. 2012;86(5):2706–14. Scholar
  61. 61.
    Schrauwen EJA, Bestebroer TM, Munster VJ, de Wit E, Herfst S, Rimmelzwaan GF, et al. Insertion of a multibasic cleavage site in the haemagglutinin of human influenza H3N2 virus does not increase pathogenicity in ferrets. J Gen Virol. 2011;92(Pt 6):1410–5. Scholar
  62. 62.
    Ji Y, White YJ, Hadden JA, Grant OC, Woods RJ. New insights into influenza A specificity: an evolution of paradigms. Curr Opin Struct Biol. 2017;44:219–31. Scholar
  63. 63.
    Wagner R, Matrosovich M, Klenk H-D. Functional balance between haemagglutinin and neuraminidase in influenza virus infections. Rev Med Virol. 2002;12(3):159–66. Scholar
  64. 64.
    Matsuoka Y, Swayne DE, Thomas C, Rameix-Welti MA, Naffakh N, Warnes C, et al. Neuraminidase stalk length and additional glycosylation of the hemagglutinin influence the virulence of influenza H5N1 viruses for mice. J Virol. 2009;83(9):4704–8. Scholar
  65. 65.
    Hoffmann TW, Munier S, Larcher T, Soubieux D, Ledevin M, Esnault E, et al. Length variations in the NA stalk of an H7N1 influenza virus have opposite effects on viral excretion in chickens and ducks. J Virol. 2012;86(1):584–8. Scholar
  66. 66.
    Zhou H, Yu Z, Hu Y, et al. The special neuraminidase stalk-motif responsible for increased virulence and pathogenesis of H5N1 influenza A virus. Martin DP, ed. PLoS One. 2009;4(7):e6277. doi:
  67. 67.
    Wang D, Yang L, Gao R, et al. Genetic tuning of the novel avian influenza A(H7N9) virus during interspecies transmission, China, 2013. Euro Surveill. 2014;19(25).Google Scholar
  68. 68.
    Fouchier RA, Schneeberger PM, Rozendaal FW, et al. Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. Proc Natl Acad Sci U S A. 2004;101(5):1356–61. Scholar
  69. 69.
    Blumenkrantz D, Roberts KL, Shelton H, Lycett S, Barclay WS. The short stalk length of highly pathogenic avian influenza H5N1 virus neuraminidase limits transmission of pandemic H1N1 virus in ferrets. J Virol. 2013;87(19):10539–51. Scholar
  70. 70.
    Kawaoka Y, Krauss S, Webster RG. Avian-to-human transmission of the PB1 gene of influenza A viruses in the 1957 and 1968 pandemics. J Virol. 1989;63(11):4603–8.PubMedPubMedCentralGoogle Scholar
  71. 71.
    Ito T, Couceiro JN, Kelm S, Baum LG, Krauss S, Castrucci MR, et al. Molecular basis for the generation in pigs of influenza A viruses with pandemic potential. J Virol. 1998;72(9):7367–73.PubMedPubMedCentralGoogle Scholar
  72. 72.
    Makarova NV, Ozaki H, Kida H, Webster RG, Perez DR. Replication and transmission of influenza viruses in Japanese quail. Virology. 2003;310(1):8–15.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Hossain MJ, Hickman D, Perez DR. Evidence of expanded host range and mammalian-associated genetic changes in a duck H9N2 influenza virus following adaptation in quail and chickens. Montgomery JM, ed. PLoS One. 2008;3(9):e3170. doi:
  74. 74.
    Giannecchini S, Clausi V, Di Trani L, et al. Molecular adaptation of an H7N3 wild duck influenza virus following experimental multiple passages in quail and turkey. Virology. 2010;408(2):167–73. Scholar
  75. 75.
    Yamada S, Shinya K, Takada A, Ito T, Suzuki T, Suzuki Y, et al. Adaptation of a duck influenza A virus in quail. J Virol. 2012;86(3):1411–20. Scholar
  76. 76.
    Thontiravong A, Kitikoon P, Wannaratana S, Tantilertcharoen R, Tuanudom R, Pakpinyo S, et al. Quail as a potential mixing vessel for the generation of new reassortant influenza A viruses. Vet Microbiol. 2012;160(3–4):305–13. Scholar
  77. 77.
    Naffakh N, Tomoiu A, Rameix-Welti M-A, van der Werf S. Host restriction of avian influenza viruses at the level of the ribonucleoproteins. Annu Rev Microbiol. 2008;62(1):403–24. Scholar
  78. 78.
    Freidl GS, Meijer A, de Bruin E, et al. Influenza at the animal-human interface: a review of the literature for virological evidence of human infection with swine or avian influenza viruses other than A(H5N1). Euro Surveill. 2014;19(18).Google Scholar
  79. 79.
    Scholtissek C, Stech J, Krauss S, Webster RG. Cooperation between the hemagglutinin of avian viruses and the matrix protein of human influenza A viruses. J Virol. 2002;76(4):1781–6.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Murphy BR, Buckler-White AJ, London WT, Harper J, Tierney EL, Miller NT, et al. Avian-human reassortant influenza A viruses derived by mating avian and human influenza A viruses. J Infect Dis. 1984;150(6):841–50.PubMedCrossRefGoogle Scholar
  81. 81.
    Imai M, Watanabe T, Hatta M, Das SC, Ozawa M, Shinya K, et al. Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature. 2012;486(7403):420–8. Scholar
  82. 82.
    Herfst S, Schrauwen EJA, Linster M, et al. Airborne transmission of influenza A/H5N1 virus between ferrets. Science (80). 2012;336(6088):1534–41. Scholar
  83. 83.
    Linster M, van Boheemen S, de Graaf M, Schrauwen EJA, Lexmond P, Mänz B, et al. Identification, characterization, and natural selection of mutations driving airborne transmission of A/H5N1 virus. Cell. 2014;157(2):329–39. Scholar
  84. 84.
    Zhu X, Viswanathan K, Raman R, Yu W, Sasisekharan R, Wilson IA. Structural basis for a switch in receptor binding specificity of two H5N1 hemagglutinin mutants. Cell Rep. 2015;13(8):1683–91. Scholar
  85. 85.
    Gabriel G, Klingel K, Otte A, Thiele S, Hudjetz B, Arman-Kalcek G, et al. Differential use of importin-α isoforms governs cell tropism and host adaptation of influenza virus. Nat Commun. 2011;2(1):156. Scholar
  86. 86.
    Mehle A, Doudna JA. Adaptive strategies of the influenza virus polymerase for replication in humans. Proc Natl Acad Sci U S A. 2009;106(50):21312–6. Scholar
  87. 87.
    Gabriel G, Herwig A, Klenk H-D. Interaction of polymerase subunit PB2 and NP with importin alpha1 is a determinant of host range of influenza A virus. PLoS Pathog. 2008;4(2):e11. Scholar
  88. 88.
    Le QM, Sakai-Tagawa Y, Ozawa M, Ito M, Kawaoka Y. Selection of H5N1 influenza virus PB2 during replication in humans. J Virol. 2009;83(10):5278–81. Scholar
  89. 89.
    Manz B, Schwemmle M, Brunotte L. Adaptation of avian influenza A virus polymerase in mammals to overcome the host species barrier. J Virol. 2013;87(13):7200–9. Scholar
  90. 90.
    Nelson MI, Vincent AL, Kitikoon P, Holmes EC, Gramer MR. Evolution of novel reassortant a/H3N2 influenza viruses in North American swine and humans, 2009–2011. J Virol. 2012;86(16):8872–8. Scholar
  91. 91.
    Campbell PJ, Danzy S, Kyriakis CS, Deymier MJ, Lowen AC, Steel J. The M segment of the 2009 pandemic influenza virus confers increased neuraminidase activity, filamentous morphology, and efficient contact transmissibility to A/Puerto Rico/8/1934-based reassortant viruses. J Virol. 2014;88(7):3802–14. Scholar
  92. 92.
    Campbell PJ, Kyriakis CS, Marshall N, Suppiah S, Seladi-Schulman J, Danzy S, et al. Residue 41 of the Eurasian avian-like swine influenza a virus matrix protein modulates virion filament length and efficiency of contact transmission. J Virol. 2014;88(13):7569–77. Scholar
  93. 93.
    Centers for Disease Control and Prevention. Media relations—have you heard? Archive: 2011. Available at Accessed January 5, 2018.
  94. 94.
    Claas EC, Osterhaus AD, van Beek R, et al. Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Lancet. 1998;351(9101):472–7. Scholar
  95. 95.
    Bender C, Hall H, Huang J, Klimov A, Cox N, Hay A, et al. Characterization of the surface proteins of influenza A (H5N1) viruses isolated from humans in 1997–1998. Virology. 1999;254(1):115–23. Scholar
  96. 96.
    Peiris JS, Yu WC, Leung CW, Cheung CY, Ng WF, Nicholls JM, et al. Re-emergence of fatal human influenza A subtype H5N1 disease. Lancet. 2004;363(9409):617–9. Scholar
  97. 97.
    World Health Organization. Influenza at the human-animal interface. Available at Accessed December 12, 2017.
  98. 98.
    World Health Organization. Cumulative number of confirmed human cases of avian influenza A(H5N1) reported to WHO. 2017. Available at Accessed December 14, 2017.
  99. 99.
    Uyeki TM. Human infection with highly pathogenic avian influenza A (H5N1) virus: review of clinical issues. Clin Infect Dis. 2009;49(2):279–90. Scholar
  100. 100.
    Chen Y, Liang W, Yang S, Wu N, Gao H, Sheng J, et al. Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome. Lancet. 2013;381(9881):1916–25. Scholar
  101. 101.
    World Health Organization Risk Assessment. Human infections with avian influenza A(H7N9) virus Summary of surveillance and investigation findings. 2014. Available at Accessed December 12, 2017.
  102. 102.
    Centers for Disease Control and Prevention. Summary of influenza Risk Assessment Tool (IRAT) Results. Available at Published 2017. Accessed December 12, 2017.
  103. 103.
    • Yang ZF, Mok CK, Peiris JS, Zhong NS. Human infection with a novel avian influenza A(H5N6) virus. N Engl J Med. 2015;373(5):487–9. This reference was the first to describe Human Infection with a novel Avian Influenza A(H5N6) virus.
  104. 104.
    World Health Organization. Human infections with avian influenza A(H5N6) virus—China. WHO 2016. Available at Accessed December 12, 2017.
  105. 105.
    Peiris M, Yuen KY, Leung CW, Chan KH, Ip PLS, Lai RWM, et al. Human infection with influenza H9N2. Lancet. 1999;354(9182):916–7. Scholar
  106. 106.
    Koopmans M, Wilbrink B, Conyn M, Natrop G, van der Nat H, Vennema H, et al. Transmission of H7N7 avian influenza A virus to human beings during a large outbreak in commercial poultry farms in the Netherlands. Lancet. 2004;363(9409):587–93. Scholar
  107. 107.
    Wei SH, Yang JR, Wu HS, Chang MC, Lin JS, Lin CY, et al. Human infection with avian influenza A H6N1 virus: an epidemiological analysis. Lancet Respir Med. 2013;1(10):771–8. Scholar
  108. 108.
    World Health Organization Western Pacific Region. Avian influenza A (H10N8). WPRO 2017. Available at Accessed December 12, 2017.
  109. 109.
    Glezen WP. Emerging infections: pandemic influenza. Epidemiol Rev. 1996;18(1):64–76. Scholar
  110. 110.
    Kilbourne ED. Influenza pandemics of the 20th century. Emerg Infect Dis. 2006;12(1):9–14. Scholar
  111. 111.
    Ran Z, Shen H, Lang Y, Kolb EA, Turan N, Zhu L, et al. Domestic pigs are susceptible to infection with influenza B viruses. J Virol. 2015;89(9):4818–26. Scholar
  112. 112.
    Brockwell-Staats C, Webster RG, Webby RJ. Diversity of influenza viruses in swine and the emergence of a novel human pandemic influenza A (H1N1). Influenza Other Respir Viruses. 2009;3(5):207–13. Scholar
  113. 113.
    • Rewar S, Mirdha D, Rewar P. Treatment and prevention of pandemic H1N1 influenza. Ann Glob Heal. 2015;81(5):645–53. This reference is a good resource for information regarding the treatment and prevention of pandemic H1N1 influenza.
  114. 114.
    Myers KP, Olsen CW, Gray GC. Cases of swine influenza in humans: a review of the literature. Clin Infect Dis. 2007;44(8):1084–8. Scholar
  115. 115.
    Shope RE. Swine influenza: i. Experimental transmission and pathology. J Exp Med. 1931;54(3):349–59. Accessed December 10, 2017PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Smith TF, Burgert EO, Dowdle WR, Noble GR, Campbell RJ, Van Scoy RE. Isolation of swine influenza virus from autopsy lung tissue of man. N Engl J Med. 1976;294(13):708–10. Scholar
  117. 117.
    Zimmer SM, Burke DS. Historical perspective—emergence of influenza a (H1N1) viruses. N Engl J Med. 2009;361(3):279–85. Scholar
  118. 118.
    Vincent AL, Awada L, Brown I, Chen H, Claes F, Dauphin G, et al. Review of influenza a virus in swine worldwide: a call for increased surveillance and research. Zoonoses Public Health. 2014;61(1):4–17. Scholar
  119. 119.
    Shinde V, Bridges CB, Uyeki TM, Shu B, Balish A, Xu X, et al. Triple-Reassortant swine influenza A (H1) in humans in the United States, 2005–2009. N Engl J Med. 2009;360(25):2616–25. Scholar
  120. 120.
    Cheng VC, To KK, Tse H, Hung IF, Yuen KY. Two years after pandemic influenza a/2009/H1N1: what have we learned? Clin Microbiol Rev. 2012;25(2):223–63. Scholar
  121. 121.
    •• Bui CM, Chughtai AA, Adam DC, MacIntyre CR. An overview of the epidemiology and emergence of influenza A infection in humans over time. Arch Public Heal. 2017;75(1):15. This reference describes the the epidemiology and emergence of influenza A infection in humans over time.
  122. 122.
    Shrestha SS, Swerdlow DL, Borse RH, et al. Estimating the burden of 2009 pandemic influenza A (H1N1) in the United States (April 2009–April 2010). Clin Infect Dis. 2011;52(Supplement 1):S75–82. Scholar
  123. 123.
    Lindstrom S, Garten R, Balish A, Shu B, Emery S, Berman LS, et al. Human infections with novel reassortant influenza A(H3N2)v viruses, United States, 2011. Emerg Infect Dis. 2012;18(5):834–7. Scholar
  124. 124.
    Centers for Disease Control and Prevention (National Center for Immunization and Respiratory Diseases). Case Count: Detected U.S. Human Infections with H3N2v by State since August 2011. Swine/Variant Influenza (Flu). Available at Published 2017. Accessed December 13, 2017.
  125. 125.
    Komadina N, McVernon J, Hall R, Leder K. A historical perspective of influenza a(H1N2) virus. Emerg Infect Dis. 2014;20(1):6–12. Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • L. W. Goneau
    • 1
    • 2
  • K. Mehta
    • 3
  • J. Wong
    • 3
    • 4
    • 5
  • A. G. L’Huillier
    • 3
  • J. B. Gubbay
    • 1
    • 2
    • 3
    Email author
  1. 1.Public Health Ontario LaboratoryTorontoCanada
  2. 2.University of TorontoTorontoCanada
  3. 3.Division of Infectious Diseases, Department of PaediatricsThe Hospital for Sick ChildrenTorontoCanada
  4. 4.Department of PaediatricsUniversity of TorontoTorontoCanada
  5. 5.Department of PaediatricsNorth York General HospitalTorontoCanada

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