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Journal of General Virology header logo Journal of General Virology

Volume 92, Issue 4

Genetic and antigenic characterization of H1 influenza viruses from United States swine from 2008 Open Access

Abstract

Prior to the introduction of the 2009 pandemic H1N1 virus from humans into pigs, four phylogenetic clusters (-, -, - and ) of the haemagglutinin (HA) gene from H1 influenza viruses could be found in US swine. Information regarding the antigenic relatedness of the H1 viruses was lacking due to the dynamic and variable nature of swine lineage H1. We characterized 12 H1 isolates from 2008 by using 454 genome-sequencing technology and phylogenetic analysis of all eight gene segments and by serological cross-reactivity in the haemagglutination inhibition (HI) assay. Genetic diversity was demonstrated in all gene segments, but most notably in the HA gene. The gene segments from the 2009 pandemic H1N1 formed clusters separate from North American swine lineage viruses, suggesting progenitors of the pandemic virus were not present in US pigs immediately prior to 2009. Serological cross-reactivity paired with antigenic cartography demonstrated that the viruses in the different phylogenetic clusters are also antigenically divergent.

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2011-04-01
2026-02-10

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References

  1. Ayora-Talavera, G., Shelton, H., Scull, M. A., Ren, J., Jones, I. M., Pickles, R. J. & Barclay, W. S.(2009). Mutations in H5N1 influenza virus hemagglutinin that confer binding to human tracheal airway epithelium. PLoS ONE 4, e7836.[CrossRef] [Google Scholar]
  2. Chen, W., Calvo, P. A., Malide, D., Gibbs, J., Schubert, U., Bacik, I., Basta, S., O'Neill, R., Schickli, J. & other authors(2001). A novel influenza A virus mitochondrial protein that induces cell death. Nat Med 7, 1306–1312.[CrossRef] [Google Scholar]
  3. Conenello, G. M., Zamarin, D., Perrone, L. A., Tumpey, T. & Palese, P.(2007). A single mutation in the PB1-F2 of H5N1 (HK/97) and 1918 influenza A viruses contributes to increased virulence. PLoS Pathog 3, e141.[CrossRef] [Google Scholar]
  4. Dawood, F. S., Jain, S., Finelli, L., Shaw, M. W., Lindstrom, S., Garten, R. J., Gubareva, L. V., Xu, X., Bridges, C. B. & other authors(2009). Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 360, 2605–2615.[CrossRef] [Google Scholar]
  5. de Jong, J. C., Smith, D. J., Lapedes, A. S., Donatelli, I., Campitelli, L., Barigazzi, G., Van Reeth, K., Jones, T. C., Rimmelzwaan, G. F. & other authors(2007). Antigenic and genetic evolution of swine influenza A (H3N2) viruses in Europe. J Virol 81, 4315–4322.[CrossRef] [Google Scholar]
  6. de Wit, E., Munster, V. J., van Riel, D., Beyer, W. E., Rimmelzwaan, G. F., Kuiken, T., Osterhaus, A. D. & Fouchier, R. A.(2010). Molecular determinants of adaptation of highly pathogenic avian influenza H7N7 viruses to efficient replication in the human host. J Virol 84, 1597–1606.[CrossRef] [Google Scholar]
  7. Easterday, B. C. & van Reeth, K.(1999). Swine influenza. In Diseases of Swine, pp. 277–290. Edited by Straw, B. E., D'Allaire, S., Mengeling, W. L. & Taylor, D. J.. Ames, IA. : Iowa State University Press. [Google Scholar]
  8. Fouchier, R. A., Schneeberger, P. M., Rozendaal, F. W., Broekman, J. M., Kemink, S. A., Munster, V., Kuiken, T., Rimmelzwaan, G. F., Schutten, M. & other authors(2004). 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 101, 1356–1361.[CrossRef] [Google Scholar]
  9. Fouchier, R. A., Munster, V., Wallensten, A., Bestebroer, T. M., Herfst, S., Smith, D., Rimmelzwaan, G. F., Olsen, B. & Osterhaus, A. D.(2005). Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls. J Virol 79, 2814–2822.[CrossRef] [Google Scholar]
  10. Gao, Y., Zhang, Y., Shinya, K., Deng, G., Jiang, Y., Li, Z., Guan, Y., Tian, G., Li, Y. & other authors(2009). Identification of amino acids in HA and PB2 critical for the transmission of H5N1 avian influenza viruses in a mammalian host. PLoS Pathog 5, e1000709.[CrossRef] [Google Scholar]
  11. García-Sastre, A., Egorov, A., Matassov, D., Brandt, S., Levy, D. E., Durbin, J. E., Palese, P. & Muster, T.(1998). Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems. Virology 252, 324–330.[CrossRef] [Google Scholar]
  12. Garten, R. J., Davis, C. T., Russell, C. A., Shu, B., Lindstrom, S., Balish, A., Sessions, W. M., Xu, X., Skepner, E. & other authors(2009). Antigenic and genetic characteristics of swine-origin 2009 A (H1N1) influenza viruses circulating in humans. Science 325, 197–201.[CrossRef] [Google Scholar]
  13. Geiss, G. K., Salvatore, M., Tumpey, T. M., Carter, V. S., Wang, X., Basler, C. F., Taubenberger, J. K., Bumgarner, R. E., Palese, P. & other authors(2002). Cellular transcriptional profiling in influenza A virus-infected lung epithelial cells: the role of the nonstructural NS1 protein in the evasion of the host innate defense and its potential contribution to pandemic influenza. Proc Natl Acad Sci U S A 99, 10736–10741.[CrossRef] [Google Scholar]
  14. Hale, B. G., Steel, J., Medina, R. A., Manicassamy, B., Ye, J., Hickman, D., Hai, R., Schmolke, M., Lowen, A. C. & other authors(2010). Inefficient control of host gene expression by the 2009 pandemic H1N1 influenza A virus NS1 protein. J Virol 84, 6909–6922.[CrossRef] [Google Scholar]
  15. Hatta, M., Gao, P., Halfmann, P. & Kawaoka, Y.(2001). Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 293, 1840–1842.[CrossRef] [Google Scholar]
  16. Höper, D., Hoffmann, B. & Beer, M.(2009). Simple, sensitive, and swift sequencing of complete H5N1 avian influenza virus genomes. J Clin Microbiol 47, 674–679.[CrossRef] [Google Scholar]
  17. Huang, S. W., Hsu, Y. W., Smith, D. J., Kiang, D., Tsai, H. P., Lin, K. H., Wang, S. M., Liu, C. C., Su, I. J. & Wang, J. R.(2009). Reemergence of enterovirus 71 in 2008 in Taiwan: dynamics of genetic and antigenic evolution from 1998 to 2008. J Clin Microbiol 47, 3653–3662.[CrossRef] [Google Scholar]
  18. Itoh, Y., Shinya, K., Kiso, M., Watanabe, T., Sakoda, Y., Hatta, M., Muramoto, Y., Tamura, D., Sakai-Tagawa, Y. & other authors(2009).In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature 460, 1021–1025. [Google Scholar]
  19. Lamb, R. A. & Krug, M. A.(2007).Orthomyxoviridae: the viruses and their replication. In Fields Virology, 4th edn, pp. 1487–1531. Edited by Knipe, D. M. & Howley, P. M.. Philadelphia, PA. : Lippincott Williams & Wilkins. [Google Scholar]
  20. Le, Q. M., Kiso, M., Someya, K., Sakai, Y. T., Nguyen, T. H., Nguyen, K. H., Pham, N. D., Ngyen, H. H., Yamada, S. & other authors(2005). Avian flu: isolation of drug-resistant H5N1 virus. Nature 437, 1108.[CrossRef] [Google Scholar]
  21. Li, Z., Chen, H., Jiao, P., Deng, G., Tian, G., Li, Y., Hoffmann, E., Webster, R. G., Matsuoka, Y. & Yu, K.(2005). Molecular basis of replication of duck H5N1 influenza viruses in a mammalian mouse model. J Virol 79, 12058–12064.[CrossRef] [Google Scholar]
  22. Lipatov, A. S., Andreansky, S., Webby, R. J., Hulse, D. J., Rehg, J. E., Krauss, S., Perez, D. R., Doherty, P. C., Webster, R. G. & Sangster, M. Y.(2005). Pathogenesis of Hong Kong H5N1 influenza virus NS gene reassortants in mice: the role of cytokines and B- and T-cell responses. J Gen Virol 86, 1121–1130.[CrossRef] [Google Scholar]
  23. Long, J. X., Peng, D. X., Liu, Y. L., Wu, Y. T. & Liu, X. F.(2008). Virulence of H5N1 avian influenza virus enhanced by a 15-nucleotide deletion in the viral nonstructural gene. Virus Genes 36, 471–478.[CrossRef] [Google Scholar]
  24. Ma, W., Lager, K. M., Lekcharoensuk, P., Ulery, E. S., Janke, B. H., Solórzano, A., Webby, R. J., García-Sastre, A. & Richt, J. A.(2010). Viral reassortment and transmission after co-infection of pigs with classical H1N1 and triple-reassortant H3N2 swine influenza viruses. J Gen Virol 91, 2314–2321.[CrossRef] [Google Scholar]
  25. Manicassamy, B., Medina, R. A., Hai, R., Tsibane, T., Stertz, S., Nistal-Villán, E., Palese, P., Basler, C. F. & García-Sastre, A.(2010). Protection of mice against lethal challenge with 2009 H1N1 influenza A virus by 1918-like and classical swine H1N1 based vaccines. PLoS Pathog 6, e1000745.[CrossRef] [Google Scholar]
  26. Marozin, S., Gregory, V., Cameron, K., Bennett, M., Valette, M., Aymard, M., Foni, E., Barigazzi, G., Lin, Y. & Hay, A.(2002). Antigenic and genetic diversity among swine influenza A H1N1 and H1N2 viruses in Europe. J Gen Virol 83, 735–745. [Google Scholar]
  27. Matrosovich, M., Tuzikov, A., Bovin, N., Gambaryan, A., Klimov, A., Castrucci, M. R., Donatelli, I. & Kawaoka, Y.(2000). Early alterations of the receptor-binding properties of H1, H2, and H3 avian influenza virus hemagglutinins after their introduction into mammals. J Virol 74, 8502–8512.[CrossRef] [Google Scholar]
  28. McAuley, J. L., Hornung, F., Boyd, K. L., Smith, A. M., McKeon, R., Bennink, J., Yewdell, J. W. & McCullers, J. A.(2007). Expression of the 1918 influenza A virus PB1-F2 enhances the pathogenesis of viral and secondary bacterial pneumonia. Cell Host Microbe 2, 240–249.[CrossRef] [Google Scholar]
  29. Mehle, A. & Doudna, J. A.(2009). Adaptive strategies of the influenza virus polymerase for replication in humans. Proc Natl Acad Sci U S A 106, 21312–21316.[CrossRef] [Google Scholar]
  30. 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. & other authors(2009). Pathogenesis and transmission of swine-origin 2009 A(H1N1) influenza virus in ferrets. Science 325, 481–483. [Google Scholar]
  31. Neumann, G. & Kawaoka, Y.(2006). Host range restriction and pathogenicity in the context of influenza pandemic. Emerg Infect Dis 12, 881–886.[CrossRef] [Google Scholar]
  32. Nicholls, J. M., Chan, R. W., Russell, R. J., Air, G. M. & Peiris, J. S.(2008). Evolving complexities of influenza virus and its receptors. Trends Microbiol 16, 149–157.[CrossRef] [Google Scholar]
  33. Park, A. W., Daly, J. M., Lewis, N. S., Smith, D. J., Wood, J. L. & Grenfell, B. T.(2009). Quantifying the impact of immune escape on transmission dynamics of influenza. Science 326, 726–728.[CrossRef] [Google Scholar]
  34. Ramakrishnan, M. A., Tu, Z. J., Singh, S., Chockalingam, A. K., Gramer, M. R., Wang, P., Goyal, S. M., Yang, M., Halvorson, D. A. & Sreevatsan, S.(2009). The feasibility of using high resolution genome sequencing of influenza A viruses to detect mixed infections and quasispecies. PLoS ONE 4, e7105.[CrossRef] [Google Scholar]
  35. Röhm, C., Zhou, N., Süss, J., Mackenzie, J. & Webster, R. G.(1996). Characterization of a novel influenza hemagglutinin, H15: criteria for determination of influenza A subtypes. Virology 217, 508–516.[CrossRef] [Google Scholar]
  36. Russell, C. A., Jones, T. C., Barr, I. G., Cox, N. J., Garten, R. J., Gregory, V., Gust, I. D., Hampson, A. W., Hay, A. J. & other authors(2008). The global circulation of seasonal influenza A (H3N2) viruses. Science 320, 340–346.[CrossRef] [Google Scholar]
  37. Salomon, R., Franks, J., Govorkova, E. A., Ilyushina, N. A., Yen, H. L., Hulse-Post, D. J., Humberd, J., Trichet, M., Rehg, J. E. & other authors(2006). The polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A/Vietnam/1203/04. J Exp Med 203, 689–697.[CrossRef] [Google Scholar]
  38. Seo, S. H., Hoffmann, E. & Webster, R. G.(2002). Lethal H5N1 influenza viruses escape host anti-viral cytokine responses. Nat Med 8, 950–954.[CrossRef] [Google Scholar]
  39. Seo, S. H., Webby, R. & 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.[CrossRef] [Google Scholar]
  40. Shinya, K., Ebina, M., Yamada, S., Ono, M., Kasai, N. & Kawaoka, Y.(2006). Avian flu: influenza virus receptors in the human airway. Nature 440, 435–436.[CrossRef] [Google Scholar]
  41. Skehel, J. J. & Wiley, D. C.(2000). Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem 69, 531–569.[CrossRef] [Google Scholar]
  42. Smith, D. J., Lapedes, A. S., de Jong, J. C., Bestebroer, T. M., Rimmelzwaan, G. F., Osterhaus, A. D. & Fouchier, R. A.(2004). Mapping the antigenic and genetic evolution of influenza virus. Science 305, 371–376.[CrossRef] [Google Scholar]
  43. Spackman, E. & Suarez, D. L.(2008). Type A influenza virus detection and quantitation by real-time RT-PCR. Methods Mol Biol 436, 19–26. [Google Scholar]
  44. Steel, J., Lowen, A. C., Mubareka, S. & 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.[CrossRef] [Google Scholar]
  45. Subbarao, E. K., London, W. & Murphy, B. R.(1993). A single amino acid in the PB2 gene of influenza A virus is a determinant of host range. J Virol 67, 1761–1764. [Google Scholar]
  46. Tamura, K., Dudley, J., Nei, M. & Kumar, S.(2007).mega4: Molecular Evolutionary Genetics Analysis (mega) software version 4.0. Mol Biol Evol 24, 1596–1599.[CrossRef] [Google Scholar]
  47. Tarendeau, F., Crepin, T., Guilligay, D., Ruigrok, R. W., Cusack, S. & Hart, D. J.(2008). Host determinant residue lysine 627 lies on the surface of a discrete, folded domain of influenza virus polymerase PB2 subunit. PLoS Pathog 4, e1000136.[CrossRef] [Google Scholar]
  48. Van Hoeven, N., Pappas, C., Belser, J. A., Maines, T. R., Zeng, H., García-Sastre, A., Sasisekharan, R., Katz, J. M. & Tumpey, T. M.(2009). Human HA and polymerase subunit PB2 proteins confer transmission of an avian influenza virus through the air. Proc Natl Acad Sci U S A 106, 3366–3371.[CrossRef] [Google Scholar]
  49. Vincent, A. L., Lager, K. M., Ma, W., Lekcharoensuk, P., Gramer, M. R., Loiacono, C. & Richt, J. A.(2006). Evaluation of hemagglutinin subtype 1 swine influenza viruses from the United States. Vet Microbiol 118, 212–222.[CrossRef] [Google Scholar]
  50. Vincent, A. L., Ma, W., Lager, K. M., Janke, B. H. & Richt, J. A.(2008). Swine influenza viruses a North American perspective. Adv Virus Res 72, 127–154. [Google Scholar]
  51. Vincent, A. L., Ma, W., Lager, K. M., Gramer, M. R., Richt, J. A. & Janke, B. H.(2009a). Characterization of a newly emerged genetic cluster of H1N1 and H1N2 swine influenza virus in the United States. Virus Genes 39, 176–185.[CrossRef] [Google Scholar]
  52. Vincent, A. L., Swenson, S. L., Lager, K. M., Gauger, P. C., Loiacono, C. & Zhang, Y.(2009b). Characterization of an influenza A virus isolated from pigs during an outbreak of respiratory disease in swine and people during a county fair in the United States. Vet Microbiol 137, 51–59.[CrossRef] [Google Scholar]
  53. Vincent, A. L., Lager, K. M., Faaberg, K. S., Harland, M., Zanella, E. L., Ciacci-Zanella, J. R., Kehrli, M. E., Jr, Janke, B. H. & Klimov, A.(2010). Experimental inoculation of pigs with pandemic H1N1 2009 virus and HI cross-reactivity with contemporary swine influenza virus antisera. Influenza Other Respir Viruses 4, 53–60.[CrossRef] [Google Scholar]
  54. Webster, R. G., Bean, W. J., Gorman, O. T., Chambers, T. M. & Kawaoka, Y.(1992). Evolution and ecology of influenza A viruses. Microbiol Rev 56, 152–179. [Google Scholar]
  55. Wise, H. M., Foeglein, A., Sun, J., Dalton, R. M., Patel, S., Howard, W., Anderson, E. C., Barclay, W. S. & Digard, P.(2009). A complicated message: identification of a novel PB1-related protein translated from influenza A virus segment 2 mRNA. J Virol 83, 8021–8031.[CrossRef] [Google Scholar]
  56. Yamada, S., Hatta, M., Staker, B. L., Watanabe, S., Imai, M., Shinya, K., Sakai-Tagawa, Y., Ito, M., Ozawa, M. & other authors(2010). Biological and structural characterization of a host-adapting amino acid in influenza virus. PLoS Pathog 6, e1001034.[CrossRef] [Google Scholar]
  57. Zamarin, D., Ortigoza, M. B. & Palese, P.(2006). Influenza A virus PB1-F2 protein contributes to viral pathogenesis in mice. J Virol 80, 7976–7983.[CrossRef] [Google Scholar]
  58. Zhou, N. N., Senne, D. A., Landgraf, J. S., Swenson, S. L., Erickson, G., Rossow, K., Liu, L., Yoon, K., Krauss, S. & Webster, R. G.(1999). Genetic reassortment of avian, swine, and human influenza A viruses in American pigs. J Virol 73, 8851–8856. [Google Scholar]
  59. Zhu, H., Wang, J., Wang, P., Song, W., Zheng, Z., Chen, R., Guo, K., Zhang, T., Peiris, J. S. & Chen, H.(2010). Substitution of lysine at 627 position in PB2 protein does not change virulence of the 2009 pandemic H1N1 virus in mice. Virology 401, 1–5.[CrossRef] [Google Scholar]
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Genetic and antigenic characterization of H1 influenza viruses from United States swine from 2008
J. Gen. Virol. 92, 919 (2011); https://doi.org/10.1099/vir.0.027557-0
/content/journal/jgv/10.1099/vir.0.027557-0
/content/journal/jgv/10.1099/vir.0.027557-0
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vol. , part 4, pp. 919 - 930

Reciprocal HI titres for individual serum samples are reported for 24 different US swine influenza viruses.

HI titres for individual serum samples.

The ratio between homologous and heterologous reciprocal HI titres for individual serum samples are reported for 24 different US H1 swine influenza viruses.

Fold-reduction compared to homologous HI titre.

Reciprocal HI titres for individual serum samples are reported for three 2009 pandemic H1N1 isolates. [Single PDF file](118 KB)

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