1887

Abstract

Highly pathogenic avian influenza virus H5N1 has spread across Eurasia and Africa, and outbreaks are now endemic in several countries, including Indonesia, Vietnam and Egypt. Continuous circulation of H5N1 virus in Egypt, from a single infected source, has led to significant genetic diversification with phylogenetically separable sublineages, providing an opportunity to study the impact of genetic evolution on viral phenotypic variation. In this study, we analysed the phylogeny of H5 haemagglutinin (HA) genes in influenza viruses isolated in Egypt from 2006 to 2011 and investigated the effect of conserved amino acid mutations in the HA genes in each of the sublineages on their antigenicity. The analysis showed that viruses in at least four sublineages still persisted in poultry in Egypt as of 2011. Using reverse genetics to generate HA-reassortment viruses with specific HA mutations, we found antigenic drift in the HA in two influenza virus sublineages, compared with the other currently co-circulating influenza virus sublineages in Egypt. Moreover, the two sublineages with significant antigenic drift were antigenically distinguishable. Our findings suggested that phylogenetically divergent H5N1 viruses, which were not antigenically cross-reactive, were co-circulating in Egypt, indicating that there was a problem in using a single influenza virus strain as seed virus to produce influenza virus vaccine in Egypt and providing data for designing more efficacious control strategies in H5N1-endemic areas.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.044032-0
2012-10-01
2024-12-05
Loading full text...

Full text loading...

/deliver/fulltext/jgv/93/10/2215.html?itemId=/content/journal/jgv/10.1099/vir.0.044032-0&mimeType=html&fmt=ahah

References

  1. Abdel-Moneim A. S., Shany S. A., Fereidouni S. R., Eid B. T., el-Kady M. F., Starick E., Harder T., Keil G. M. 2009; Sequence diversity of the haemagglutinin open reading frame of recent highly pathogenic avian influenza H5N1 isolates from Egypt. Arch Virol 154:1559–1562 [View Article][PubMed]
    [Google Scholar]
  2. Abdel-Moneim A. S., Afifi M. A., El-Kady M. F. 2011; Genetic drift evolution under vaccination pressure among H5N1 Egyptian isolates. Virol J 8:283 [View Article][PubMed]
    [Google Scholar]
  3. Abdelwhab E. M., Hafez H. M. 2011a; An overview of the epidemic of highly pathogenic H5N1 avian influenza virus in Egypt: epidemiology and control challenges. Epidemiol Infect 139:647–657 [View Article][PubMed]
    [Google Scholar]
  4. Abdelwhab E. M., Grund C., Aly M. M., Beer M., Harder T. C., Hafez H. M. 2011b; Multiple dose vaccination with heterologous H5N2 vaccine: immune response and protection against variant clade 2.2.1 highly pathogenic avian influenza H5N1 in broiler breeder chickens. Vaccine 29:6219–6225 [View Article][PubMed]
    [Google Scholar]
  5. Arafa A., Suarez D. L., Hassan M. K., Aly M. M. 2010; Phylogenetic analysis of hemagglutinin and neuraminidase genes of highly pathogenic avian influenza H5N1 Egyptian strains isolated from 2006 to 2008 indicates heterogeneity with multiple distinct sublineages. Avian Dis 54:1 Suppl.345–349 [View Article][PubMed]
    [Google Scholar]
  6. Balish A. L., Davis C. T., Saad M. D., El-Sayed N., Esmat H., Tjaden J. A., Earhart K. C., Ahmed L. E., Abd El-Halem M. other authors 2010; Antigenic and genetic diversity of highly pathogenic avian influenza A (H5N1) viruses isolated in Egypt. Avian Dis 54:1 Suppl.329–334 [View Article][PubMed]
    [Google Scholar]
  7. Cattoli G., Monne I., Fusaro A., Joannis T. M., Lombin L. H., Aly M. M., Arafa A. S., Sturm-Ramirez K. M., Couacy-Hymann E. other authors 2009; Highly pathogenic avian influenza virus subtype H5N1 in Africa: a comprehensive phylogenetic analysis and molecular characterization of isolates. PLoS ONE 4:e4842 [View Article][PubMed]
    [Google Scholar]
  8. Cattoli G., Milani A., Temperton N., Zecchin B., Buratin A., Molesti E., Aly M. M., Arafa A., Capua I. 2011a; Antigenic drift in H5N1 avian influenza virus in poultry is driven by mutations in major antigenic sites of the hemagglutinin molecule analogous to those for human influenza virus. J Virol 85:8718–8724 [View Article][PubMed]
    [Google Scholar]
  9. Cattoli G., Fusaro A., Monne I., Coven F., Joannis T., El-Hamid H. S., Hussein A. A., Cornelius C., Amarin N. M. other authors 2011b; Evidence for differing evolutionary dynamics of A/H5N1 viruses among countries applying or not applying avian influenza vaccination in poultry. Vaccine 29:9368–9375 [View Article][PubMed]
    [Google Scholar]
  10. Chen H., Smith G. J., Zhang S. Y., Qin K., Wang J., Li K. S., Webster R. G., Peiris J. S., Guan Y. 2005; Avian flu: H5N1 virus outbreak in migratory waterfowl. Nature 436:191–192 [View Article][PubMed]
    [Google Scholar]
  11. Chen H., Smith G. J., Li K. S., Wang J., Fan X. H., Rayner J. M., Vijaykrishna D., Zhang J. X., Zhang L. J. other authors 2006; Establishment of multiple sublineages of H5N1 influenza virus in Asia: implications for pandemic control. Proc Natl Acad Sci U S A 103:2845–2850 [View Article][PubMed]
    [Google Scholar]
  12. Couceiro J. N., Paulson J. C., Baum L. G. 1993; Influenza virus strains selectively recognize sialyloligosaccharides on human respiratory epithelium; the role of the host cell in selection of hemagglutinin receptor specificity. Virus Res 29:155–165 [View Article][PubMed]
    [Google Scholar]
  13. Di Lonardo A., Buttinelli G., Amato C., Novello F., Ridolfi B., Fiore L. 2002; Rapid methods for identification of poliovirus isolates and determination of polio neutralizing antibody titers in human sera. J Virol Methods 101:189–196 [View Article][PubMed]
    [Google Scholar]
  14. Du A., Daidoji T., Koma T., Ibrahim M. S., Nakamura S., de Silva U. C., Ueda M., Yang C. S., Yasunaga T. other authors 2009; Detection of circulating Asian H5N1 viruses by a newly established monoclonal antibody. Biochem Biophys Res Commun 378:197–202 [View Article][PubMed]
    [Google Scholar]
  15. Eladl A. E., El-Azm K. I., Ismail A. E., Ali A., Saif Y. M., Lee C. W. 2011; Genetic characterization of highly pathogenic H5N1 avian influenza viruses isolated from poultry farms in Egypt. Virus Genes 43:272–280 [View Article][PubMed]
    [Google Scholar]
  16. FAO 2011; H5N1 HPAI global overview. Accessed 4 December 2011. http://www.fao.org/avianflu/en/overview.htm
  17. Fodor E., Devenish L., Engelhardt O. G., Palese P., Brownlee G. G., García-Sastre A. 1999; Rescue of influenza A virus from recombinant DNA. J Virol 73:9679–9682[PubMed]
    [Google Scholar]
  18. Fusaro A., Nelson M. I., Joannis T., Bertolotti L., Monne I., Salviato A., Olaleye O., Shittu I., Sulaiman L. other authors 2010; Evolutionary dynamics of multiple sublineages of H5N1 influenza viruses in Nigeria from 2006 to 2008. J Virol 84:3239–3247 [View Article][PubMed]
    [Google Scholar]
  19. Grund C., Abdelwhab S. M., Arafa A. S., Ziller M., Hassan M. K., Aly M. M., Hafez H. M., Harder T. C., Beer M. 2011; Highly pathogenic avian influenza virus H5N1 from Egypt escapes vaccine-induced immunity but confers clinical protection against a heterologous clade 2.2.1 Egyptian isolate. Vaccine 29:5567–5573 [View Article][PubMed]
    [Google Scholar]
  20. Hafez M. H., Arafa A., Abdelwhab E. M., Selim A., Khoulosy S. G., Hassan M. K., Aly M. M. 2010; Avian influenza H5N1 virus infections in vaccinated commercial and backyard poultry in Egypt. Poult Sci 89:1609–1613 [View Article][PubMed]
    [Google Scholar]
  21. Hensley S. E., Das S. R., Bailey A. L., Schmidt L. M., Hickman H. D., Jayaraman A., Viswanathan K., Raman R., Sasisekharan R. other authors 2009; Hemagglutinin receptor binding avidity drives influenza A virus antigenic drift. Science 326:734–736 [View Article][PubMed]
    [Google Scholar]
  22. Horimoto T., Kawaoka Y. 2005; Influenza: lessons from past pandemics, warnings from current incidents. Nat Rev Microbiol 3:591–600 [View Article][PubMed]
    [Google Scholar]
  23. Ibrahim M. S., Watanabe Y., Ellakany H. F., Yamagishi A., Sapsutthipas S., Toyoda T., Abd El-Hamied H. S., Ikuta K. 2011; Host-specific genetic variation of highly pathogenic avian influenza viruses (H5N1). Virus Genes 42:363–368 [View Article][PubMed]
    [Google Scholar]
  24. Ito T., Couceiro J. N., Kelm S., Baum L. G., Krauss S., Castrucci M. R., Donatelli I., Kida H., Paulson J. C. other authors 1998; Molecular basis for the generation in pigs of influenza A viruses with pandemic potential. J Virol 72:7367–7373[PubMed]
    [Google Scholar]
  25. Kaminski D. A., Lee F. E. 2011; Antibodies against conserved antigens provide opportunities for reform in influenza vaccine design. Front Immunol 2:76[PubMed] [CrossRef]
    [Google Scholar]
  26. Katoh K., Misawa K., Kuma K., Miyata T. 2002; mafft: a novel method for rapid multiple sequence alignment based on fast Fourier transform. Nucleic Acids Res 30:3059–3066 [View Article][PubMed]
    [Google Scholar]
  27. Kaverin N. V., Rudneva I. A., Govorkova E. A., Timofeeva T. A., Shilov A. A., Kochergin-Nikitsky K. S., Krylov P. S., Webster R. G. 2007; Epitope mapping of the hemagglutinin molecule of a highly pathogenic H5N1 influenza virus by using monoclonal antibodies. J Virol 81:12911–12917 [View Article][PubMed]
    [Google Scholar]
  28. Kim J. K., Kayali G., Walker D., Forrest H. L., Ellebedy A. H., Griffin Y. S., Rubrum A., Bahgat M. M., Kutkat M. A. other authors 2010; Puzzling inefficiency of H5N1 influenza vaccines in Egyptian poultry. Proc Natl Acad Sci U S A 107:11044–11049 [View Article][PubMed]
    [Google Scholar]
  29. Meleigy M. 2007; Egypt battles with avian influenza. Lancet 370:553–554 [View Article][PubMed]
    [Google Scholar]
  30. Nelson M. I., Holmes E. C. 2007; The evolution of epidemic influenza. Nat Rev Genet 8:196–205 [View Article][PubMed]
    [Google Scholar]
  31. OIE 2003; The use of vaccination as an option for the control of avian influenza. Final report of the 71st general session of the OIE international committee, Paris, 18–23 May 2003. http://www.oie.int/fileadmin/Home/eng/About_us/docs/pdf/A_RFinal_2003_wp.pdf
  32. OIE 2011; Update on highly pathogenic avian influenza in animals (type H5 and H7). Accessed 4 December 2011. http://www.oie.int/animal-health-in-the-world/update-on-avian-influenza/2011/
  33. Okuno Y., Isegawa Y., Sasao F., Ueda S. 1993; A common neutralizing epitope conserved between the hemagglutinins of influenza A virus H1 and H2 strains. J Virol 67:2552–2558[PubMed]
    [Google Scholar]
  34. Peiris J. S., de Jong M. D., Guan Y. 2007; Avian influenza virus (H5N1): a threat to human health. Clin Microbiol Rev 20:243–267 [View Article][PubMed]
    [Google Scholar]
  35. Peyre M., Samaha H., Makonnen Y. J., Saad A., Abd-Elnabi A., Galal S., Ettel T., Dauphin G., Lubroth J. other authors 2009; Avian influenza vaccination in Egypt: limitations of the current strategy. J Mol Genet Med 3:198–204[PubMed]
    [Google Scholar]
  36. Saad M. D., Ahmed L. S., Gamal-Eldein M. A., Fouda M. K., Khalil F., Yingst S. L., Parker M. A., Montevillel M. R. 2007; Possible avian influenza (H5N1) from migratory bird, Egypt. Emerg Infect Dis 13:1120–1121 [View Article][PubMed]
    [Google Scholar]
  37. Salzberg S. L., Kingsford C., Cattoli G., Spiro D. J., Janies D. A., Aly M. M., Brown I. H., Couacy-Hymann E., De Mia G. M. other authors 2007; Genome analysis linking recent European and African influenza (H5N1) viruses. Emerg Infect Dis 13:713–718 [View Article][PubMed]
    [Google Scholar]
  38. Skehel J. J., Wiley D. C. 2000; Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem 69:531–569 [View Article][PubMed]
    [Google Scholar]
  39. Skehel J. J., Stevens D. J., Daniels R. S., Douglas A. R., Knossow M., Wilson I. A., Wiley D. C. 1984; A carbohydrate side chain on hemagglutinins of Hong Kong influenza viruses inhibits recognition by a monoclonal antibody. Proc Natl Acad Sci U S A 81:1779–1783 [View Article][PubMed]
    [Google Scholar]
  40. Smirnov Y. A., Lipatov A. S., Gitelman A. K., Okuno Y., Van Beek R., Osterhaus A. D., Claas E. C. 1999; An epitope shared by the hemagglutinins of H1, H2, H5, and H6 subtypes of influenza A virus. Acta Virol 43:237–244[PubMed]
    [Google Scholar]
  41. Smith A. E., Helenius A. 2004; How viruses enter animal cells. Science 304:237–242 [View Article][PubMed]
    [Google Scholar]
  42. Smith G. J., Fan X. H., Wang J., Li K. S., Qin K., Zhang J. X., Vijaykrishna D., Cheung C. L., Huang K. other authors 2006; Emergence and predominance of an H5N1 influenza variant in China. Proc Natl Acad Sci U S A 103:16936–16941 [View Article][PubMed]
    [Google Scholar]
  43. Stevens J., Blixt O., Tumpey T. M., Taubenberger J. K., Paulson J. C., Wilson I. A. 2006; Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus. Science 312:404–410 [View Article][PubMed]
    [Google Scholar]
  44. Suarez D. L. 2010; Avian influenza: our current understanding. Anim Health Res Rev 11:19–33 [View Article][PubMed]
    [Google Scholar]
  45. Suzuki Y. 2005; Sialobiology of influenza: molecular mechanism of host range variation of influenza viruses. Biol Pharm Bull 28:399–408 [View Article][PubMed]
    [Google Scholar]
  46. Swayne D. E. 2009; Avian influenza vaccines and therapies for poultry. Comp Immunol Microbiol Infect Dis 32:351–363 [View Article][PubMed]
    [Google Scholar]
  47. Swayne D. E., Kapczynski D. 2008; Strategies and challenges for eliciting immunity against avian influenza virus in birds. Immunol Rev 225:314–331 [View Article][PubMed]
    [Google Scholar]
  48. 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 [View Article][PubMed]
    [Google Scholar]
  49. Terregino C., Toffan A., Cilloni F., Monne I., Bertoli E., Castellanos L., Amarin N., Mancin M., Capua I. 2010; Evaluation of the protection induced by avian influenza vaccines containing a 1994 Mexican H5N2 LPAI seed strain against a 2008 Egyptian H5N1 HPAI virus belonging to clade 2.2.1 by means of serological and in vivo tests. Avian Pathol 39:215–222 [View Article][PubMed]
    [Google Scholar]
  50. Wang G., Zhan D., Li L., Lei F., Liu B., Liu D., Xiao H., Feng Y., Li J. other authors 2008; H5N1 avian influenza re-emergence of Lake Qinghai: phylogenetic and antigenic analyses of the newly isolated viruses and roles of migratory birds in virus circulation. J Gen Virol 89:697–702 [View Article][PubMed]
    [Google Scholar]
  51. Wang W., Lu B., Zhou H., Suguitan A. L. Jr, Cheng X., Subbarao K., Kemble G., Jin H. 2010; Glycosylation at 158N of the hemagglutinin protein and receptor binding specificity synergistically affect the antigenicity and immunogenicity of a live attenuated H5N1 A/Vietnam/1203/2004 vaccine virus in ferrets. J Virol 84:6570–6577 [View Article][PubMed]
    [Google Scholar]
  52. Watanabe Y., Ibrahim M. S., Hagiwara K., Okamoto M., Kamitani W., Yanai H., Ohtaki N., Hayashi Y., Taniyama H. other authors 2007; Characterization of a Borna disease virus field isolate which shows efficient viral propagation and transmissibility. Microbes Infect 9:417–427 [View Article][PubMed]
    [Google Scholar]
  53. Watanabe Y., Ohtaki N., Hayashi Y., Ikuta K., Tomonaga K. 2009; Autogenous translational regulation of the Borna disease virus negative control factor X from polycistronic mRNA using host RNA helicases. PLoS Pathog 5:e1000654 [View Article][PubMed]
    [Google Scholar]
  54. Watanabe Y., Ibrahim M. S., Ellakany H. F., Abd El-Hamid H. S., Ikuta K. 2011a; Genetic diversification of H5N1 highly pathogenic avian influenza A virus during replication in wild ducks. J Gen Virol 92:2105–2110 [View Article][PubMed]
    [Google Scholar]
  55. Watanabe Y., Ibrahim M. S., Ellakany H. F., Kawashita N., Mizuike R., Hiramatsu H., Sriwilaijaroen N., Takagi T., Suzuki Y., Ikuta K. 2011b; Acquisition of human-type receptor binding specificity by new H5N1 influenza virus sublineages during their emergence in birds in Egypt. PLoS Pathog 7:e1002068 [View Article][PubMed]
    [Google Scholar]
  56. Watanabe Y., Ibrahim M. S., Suzuki Y., Ikuta K. 2012; The changing nature of avian influenza A virus (H5N1). Trends Microbiol 20:11–20 [View Article][PubMed]
    [Google Scholar]
  57. WHO 2012a; Cumulative number of confirmed human cases of avian influenza A(H5N1) reported to WHO. Accessed 2 April 2012. http://www.who.int/influenza/human_animal_interface/H5N1_cumulative_table_archives/en/index.html
  58. WHO 2012b; Global alert and response: disease outbreak news. Accessed 2 April 2012. http://www.who.int/csr/don/en/
  59. WHO 2012c; H5N1 avian influenza: timeline of major events. Accessed 14 March 2012. http://www.who.int/influenza/human_animal_interface/avian_influenza/H5N1_avian_influenza_update140312.pdf
  60. WHO/OIE/FAO H5N1 Evolution Working Group 2008; Toward a unified nomenclature system for highly pathogenic avian influenza virus (H5N1). Emerg Infect Dis 14:e1[PubMed]
    [Google Scholar]
  61. Wibawa H., Henning J., Wong F., Selleck P., Junaidi A., Bingham J., Daniels P., Meers J. 2011; A molecular and antigenic survey of H5N1 highly pathogenic avian influenza virus isolates from smallholder duck farms in Central Java, Indonesia during 2007–2008. Virol J 8:425 [View Article][PubMed]
    [Google Scholar]
  62. Wiley D. C., Wilson I. A., Skehel J. J. 1981; Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature 289:373–378 [View Article][PubMed]
    [Google Scholar]
/content/journal/jgv/10.1099/vir.0.044032-0
Loading
/content/journal/jgv/10.1099/vir.0.044032-0
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error