Skip to main content
Log in

Diversifying evolution of highly pathogenic H5N1 avian influenza virus in Egypt from 2006 to 2011

  • Published:
Virus Genes Aims and scope Submit manuscript

Abstract

An evolutionary analysis was conducted of 354 hemagglutinin (HA) and 208 neuraminidase (NA) genes, including newly generated sequences of 5 HA and 30 NA, of Egyptian H5N1 clade 2.2.1 viruses isolated from poultry and humans. Five distinct phylogenetically distinguishable clusters arose from a monophyletic origin since 2006. Only two clusters remained in circulation after 2009: (i) A cluster of viruses arose in 2007 in industrial-vaccinated chickens and carried multiple mutations in or adjacent to the immunogenic epitopes of the HA. Viruses within this cluster evolved with significantly elevated mutation rates indicating persisting selective pressures, e.g. to escape host immunity and (ii) The second group arose in 2008 and harboured strains from recent human infections featuring a conspicuous deletion in the HA receptor-binding domain and substitutions close to the highly conserved active site of the NA. In both sublineages, a number of positively selected amino acids, different glycosylation patterns and variations in the polybasic proteolytic cleavage site were observed. Continuous monitoring of the evolving H5N1 virus in Egypt is essential to develop new control campaigns in poultry and human population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. L.D. Sims, T.M. Ellis, K.K. Liu, K. Dyrting, H. Wong, M. Peiris, Y. Guan, K.F. Shortridge, Avian. Dis. 47, 832–838 (2003)

    Article  PubMed  CAS  Google Scholar 

  2. L. Duan, J. Bahl, G.J. Smith, J. Wang, D. Vijaykrishna, L.J. Zhang, J.X. Zhang, K.S. Li, X.H. Fan, C.L. Cheung, K. Huang, L.L. Poon, K.F. Shortridge, R.G. Webster, J.S. Peiris, H. Chen, Y. Guan, Virology 380, 243–254 (2008)

    Article  PubMed  CAS  Google Scholar 

  3. G.J. Smith, T.S. Naipospos, T.D. Nguyen, M.D. de Jong, D. Vijaykrishna, T.B. Usman, S.S. Hassan, T.V. Nguyen, T.V. Dao, N.A. Bui, Y.H. Leung, C.L. Cheung, J.M. Rayner, J.X. Zhang, L.J. Zhang, L.L. Poon, K.S. Li, V.C. Nguyen, T.T. Hien, J. Farrar, R.G. Webster, H. Chen, J.S. Peiris, Y. Guan, Virology 350, 258–268 (2006)

    Article  PubMed  CAS  Google Scholar 

  4. S.L. Salzberg, C. Kingsford, G. Cattoli, D.J. Spiro, D.A. Janies, M.M. Aly, I.H. Brown, E. Couacy-Hymann, G.M. De Mia, H. do Dung, A. Guercio, T. Joannis, A.S. Maken Ali, A. Osmani, I. Padalino, M.D. Saad, V. Savic, N.A. Sengamalay, S. Yingst, J. Zaborsky, O. Zorman-Rojs, E. Ghedin, I. Capua, Emerg. Infect. Dis. 13, 713–718 (2007)

    Article  PubMed  CAS  Google Scholar 

  5. M. Gilbert, P. Chaitaweesub, T. Parakamawongsa, S. Premashthira, T. Tiensin, W. Kalpravidh, H. Wagner, J. Slingenbergh, Emerg. Infect. Dis. 12, 227–234 (2006)

    Article  PubMed  Google Scholar 

  6. L.D. Sims, J. Domenech, C. Benigno, S. Kahn, A. Kamata, J. Lubroth, V. Martin, P. Roeder, Vet. Rec. 157, 159–164 (2005)

    PubMed  CAS  Google Scholar 

  7. M.M. Aly, A. Arafa, M.K. Hassan, Avian. Dis. 52, 269–277 (2008)

    Article  PubMed  CAS  Google Scholar 

  8. M.D. Saad, L.S. Ahmed, M.A. Gamal-Eldein, M.K. Fouda, F. Khalil, S.L. Yingst, M.A. Parker, M.R. Montevillel, Emerg. Infect. Dis. 13, 1120–1121 (2007)

    Article  PubMed  Google Scholar 

  9. E.M. Abdelwhab, H.M. Hafez, Epidemiol. Infect. 139, 647–657 (2011)

    Article  PubMed  CAS  Google Scholar 

  10. M.H. Hafez, A. Arafa, E.M. Abdelwhab, A. Selim, S.G. Khoulosy, M.K. Hassan, M.M. Aly, Poult. Sci. 89, 1609–1613 (2010)

    Article  PubMed  CAS  Google Scholar 

  11. A. Arafa, D.L. Suarez, M.K. Hassan, M.M. Aly, Avian. Dis. 54, 345–349 (2010)

    Article  PubMed  CAS  Google Scholar 

  12. G. Cattoli, A. Milani, N. Temperton, B. Zecchin, A. Buratin, E. Molesti, M.M. Aly, A. Arafa, I. Capua, J. Virol. 85, 8718–8724 (2011)

    Article  PubMed  CAS  Google Scholar 

  13. WHO/OIE/FAO H5N1 Evolution Working Group, Influenza Other Respi Viruses 6: 1–5, 2012 http://onlinelibrary.wiley.com/doi/10.1111/j.1750-2659.2011.00298.x/pdf

  14. A.L. Balish, C.T. Davis, M.D. Saad, N. El-Sayed, H. Esmat, J.A. Tjaden, K.C. Earhart, L.E. Ahmed, Abd. El-M.Halem, A.H. Ali, S.A. Nassif, E.A. El-Ebiary, M. Taha, M.M. Aly, A. Arafa, E. O’Neill, X. Xiyan, N.J. Cox, R.O. Donis, A.I. Klimov, Avian. Dis. 54, 329–334 (2010)

    Article  PubMed  Google Scholar 

  15. World Health Organization (WHO), 2011 http://www.who.int/influenza/human_animal_interface/EN_GIP_20120312uCumulativeNumberH5N1cases.pdf

  16. A. Kandeel, S. Manoncourt, E. el Abd Kareem, A.N. Mohamed Ahmed, S. El-Refaie, H. Essmat, J. Tjaden, C.C. de Mattos, K.C. Earhart, A.A. Marfin, N. El-Sayed, Emerg. Infect. Dis. 16, 1101–1107 (2010)

    Article  PubMed  Google Scholar 

  17. A.S. Abdel-Moneim, A.E. Abdel-Ghany, S.A. Shany, J. Biomed. Sci. 17, 25 (2010)

    Article  PubMed  Google Scholar 

  18. E.M. Abdelwhab, A.A. Selim, A. Arafa, S. Galal, W.H. Kilany, M.K. Hassan, M.M. Aly, M.H. Hafez, Avian. Dis. 54, 911–914 (2010)

    Article  PubMed  CAS  Google Scholar 

  19. A. El-Sayed, W. Awad, A. Fayed, H.P. Hamann, M. Zschock, Emerg. Infect. Dis. 16, 726–727 (2010)

    PubMed  Google Scholar 

  20. K. Katoh, G. Asimenos, H. Toh, Methods. Mol. Biol. 537, 39–64 (2009)

    Article  PubMed  CAS  Google Scholar 

  21. T.A. Hall, Nucleic. Acids. Symp. Ser. 41, 95–98 (1999)

    CAS  Google Scholar 

  22. I. Milne, D. Lindner, M. Bayer, D. Husmeier, G. McGuire, D.F. Marshall, F. Wright, Bioinformatics 25, 126–127 (2009)

    Article  PubMed  CAS  Google Scholar 

  23. D.H. Huson, D.C. Richter, C. Rausch, T. Dezulian, M. Franz, R. Rupp, BMC. Bioinformatics. 8, 460 (2007)

    Article  PubMed  Google Scholar 

  24. A.J. Drummond, A. Rambaut, BMC. Evol. Biol. 7, 214 (2007)

    Article  PubMed  Google Scholar 

  25. K. Tamura, J. Dudley, M. Nei, S. Kumar, Mol. Biol. Evol. 24, 1596–1599 (2007)

    Article  PubMed  CAS  Google Scholar 

  26. S.L. Pond, S.D. Frost, S.V. Muse, Bioinformatics 21, 676–679 (2005)

    Article  PubMed  CAS  Google Scholar 

  27. R. Gupta, S. Brunak, Pac. Symp. Biocomput. 310–322 (2002)

  28. B. Contreras-Moreira, P.A. Bates, Bioinformatics 18, 1141–1142 (2002)

    Article  PubMed  CAS  Google Scholar 

  29. A.A. Porollo, R. Adamczak, J. Meller, Bioinformatics 20, 2460–2462 (2004)

    Article  PubMed  CAS  Google Scholar 

  30. Valadone P., Sayle, R., Mueller, A., Bernstein, H., 2010 http://wwwbernstein-plus-sonscom/software/RasMol_271/

  31. V.R. Duvvuri, B. Duvvuri, W.R. Cuff, G.E. Wu, J. Wu, Genomics. Proteomics. Bioinformatics. 7, 47–56 (2009)

    Article  PubMed  CAS  Google Scholar 

  32. C. Grund, S.M. el Abdelwhab, A.S. Arafa, M. Ziller, M.K. Hassan, M.M. Aly, H.M. Hafez, T.C. Harder, M. Beer, Vaccine 29, 5567–5573 (2011)

    Article  PubMed  CAS  Google Scholar 

  33. M. Matrosovich, N. Zhou, Y. Kawaoka, R. Webster, J. Virol. 73, 1146–1155 (1999)

    PubMed  CAS  Google Scholar 

  34. Y. Shtyrya, L. Mochalova, G. Voznova, I. Rudneva, A. Shilov, N. Kaverin, N. Bovin, Glycoconj. J. 26, 99–109 (2009)

    Article  PubMed  CAS  Google Scholar 

  35. C.C. Wang, J.R. Chen, Y.C. Tseng, C.H. Hsu, Y.F. Hung, S.W. Chen, C.M. Chen, K.H. Khoo, T.J. Cheng, Y.S. Cheng, J.T. Jan, C.Y. Wu, C. Ma, C.H. Wong, Proc. Natl. Acad. Sci. USA 106, 18137–18142 (2009)

    Article  PubMed  CAS  Google Scholar 

  36. Alexander D.J., World Organisation for Animal Health, Paris, France, 2009 http://www.oie.int/eng/normes/mmanual/2008/pdf/2002.2003.2004AI.pdf

  37. E.A. Govorkova, N.A. Ilyushina, B.M. Marathe, J.L. McClaren, R.G. Webster, J. Virol. 84, 8042–8050 (2010)

    Article  PubMed  CAS  Google Scholar 

  38. V.M. Deyde, T. Nguyen, R.A. Bright, A. Balish, B. Shu, S. Lindstrom, A.I. Klimov, L.V. Gubareva, Antimicrob. Agents. Chemother. 53, 1039–1047 (2009)

    Article  PubMed  CAS  Google Scholar 

  39. A.C. Hurt, J.K. Holien, I.G. Barr, Antimicrob. Agents. Chemother. 53, 4433–4440 (2009)

    Article  PubMed  CAS  Google Scholar 

  40. N.A. Ilyushina, J.P. Seiler, J.E. Rehg, R.G. Webster, E.A. Govorkova, PLoS Pathog 6, e1000933 (2010)

    Article  PubMed  Google Scholar 

  41. K.C. Earhart, N.M. Elsayed, M.D. Saad, L.V. Gubareva, A. Nayel, V.M. Deyde, A. Abdelsattar, A.S. Abdelghani, B.R. Boynton, M.M. Mansour, H.M. Essmat, A. Klimov, D. Shuck-Lee, M.R. Monteville, J.A. Tjaden, J. Infect. Public Health 2, 74–80 (2009)

    Article  PubMed  Google Scholar 

  42. G. Kayali, R.J. Webby, M.F. Ducatez, R.A. El Shesheny, A.M. Kandeil, E.A. Govorkova, A. Mostafa, M.A. Ali, PLoS ONE 6, e17730 (2011)

    Article  PubMed  CAS  Google Scholar 

  43. H.L. Yen, E. Hoffmann, G. Taylor, C. Scholtissek, A.S. Monto, R.G. Webster, E.A. Govorkova, J. Virol. 80, 8787–8795 (2006)

    Article  PubMed  CAS  Google Scholar 

  44. P.M. Colman, P.A. Hoyne, M.C. Lawrence, J. Virol. 67, 2972–2980 (1993)

    PubMed  CAS  Google Scholar 

  45. J. Uhlendorff, T. Matrosovich, H.D. Klenk, M. Matrosovich, Arch. Virol. 154, 945–957 (2009)

    Article  PubMed  CAS  Google Scholar 

  46. G. Cattoli, I. Monne, A. Fusaro, T.M. Joannis, L.H. Lombin, M.M. Aly, A.S. Arafa, K.M. Sturm-Ramirez, E. Couacy-Hymann, J.A. Awuni, K.B. Batawui, K.A. Awoume, G.L. Aplogan, A. Sow, A.C. Ngangnou, I.M. El Nasri Hamza, D. Gamatie, G. Dauphin, J.M. Domenech, I. Capua, PLoS One 4, e4842 (2009)

    Article  PubMed  Google Scholar 

  47. A. Fusaro, M.I. Nelson, T. Joannis, L. Bertolotti, I. Monne, A. Salviato, O. Olaleye, I. Shittu, L. Sulaiman, L.H. Lombin, I. Capua, E.C. Holmes, G. Cattoli, J. Virol. 84, 3239–3247 (2010)

    Article  PubMed  CAS  Google Scholar 

  48. A. Leventhal, A. Ramlawi, A. Belbiesi, R.D. Balicer, BMJ 333, 856–858 (2006)

    Article  PubMed  Google Scholar 

  49. WHO/OIE/FAO H5N1 Evolution Working Group, 2011 http://www.who.int/influenza/resources/documents/2011_2002_h2015_h2019_vaccinevirusupdate.pdf

  50. D. Vijaykrishna, J. Bahl, S. Riley, L. Duan, J.X. Zhang, H. Chen, J.S. Peiris, G.J. Smith, Y. Guan, PLoS Pathog 4, e1000161 (2008)

    Article  PubMed  Google Scholar 

  51. G. Cattoli, A. Fusaro, I. Monne, F. Coven, T. Joannis, H.S. El-Hamid, A.A. Hussein, C. Cornelius, N.M. Amarin, M. Mancin, E.C. Holmes, I. Capua, Vaccine 29, 9368–9375 (2011)

    Article  PubMed  Google Scholar 

  52. N.V. Kaverin, I.A. Rudneva, E.A. Govorkova, T.A. Timofeeva, A.A. Shilov, K.S. Kochergin-Nikitsky, P.S. Krylov, R.G. Webster, J. Virol. 81, 12911–12917 (2007)

    Article  PubMed  CAS  Google Scholar 

  53. C.W. Lee, D.A. Senne, D.L. Suarez, J. Virol. 78, 8372–8381 (2004)

    Article  PubMed  CAS  Google Scholar 

  54. E.M. Abdelwhab, C. Grund, M.M. Aly, M. Beer, T.C. Harder, H.M. Hafez, Vaccine 29, 6219–6225 (2011)

    Article  PubMed  CAS  Google Scholar 

  55. W.H. Kilany, E.M. Abdelwhab, A.S. Arafa, A. Selim, M. Safwat, A.A. Nawar, A.M. Erfan, M.K. Hassan, M.M. Aly, H.M. Hafez, Vet. Microbiol. 150, 28–34 (2011)

    Article  PubMed  CAS  Google Scholar 

  56. Y. Watanabe, M.S. Ibrahim, H.F. Ellakany, N. Kawashita, R. Mizuike, H. Hiramatsu, N. Sriwilaijaroen, T. Takagi, Y. Suzuki, K. Ikuta, PLoS Pathog 7, e1002068 (2011)

    Article  PubMed  CAS  Google Scholar 

  57. D.A. Boltz, B. Douangngeun, P. Phommachanh, S. Sinthasak, R. Mondry, C. Obert, P. Seiler, R. Keating, Y. Suzuki, H. Hiramatsu, E.A. Govorkova, R.G. Webster, J. Gen. Virol. 91, 949–959 (2010)

    Article  PubMed  CAS  Google Scholar 

  58. I.T. Schulze, J. Infect. Dis. 176(Suppl 1), S24–S28 (1997)

    Article  PubMed  Google Scholar 

  59. S.J. Baigent, J.W. McCauley, Virus. Res. 79, 177–185 (2001)

    Article  PubMed  CAS  Google Scholar 

  60. Y. Gao, Y. Zhang, K. Shinya, G. Deng, Y. Jiang, Z. Li, Y. Guan, G. Tian, Y. Li, J. Shi, L. Liu, X. Zeng, Z. Bu, X. Xia, Y. Kawaoka, H. Chen, PLoS Pathog 5, e1000709 (2009)

    Article  PubMed  Google Scholar 

  61. R. Chen, E.C. Holmes, Mol. Biol. Evol. 23, 2336–2341 (2006)

    Article  PubMed  CAS  Google Scholar 

  62. Y. Abed, I. Hardy, Y. Li, G. Boivin, J. Med. Virol. 67, 589–595 (2002)

    Article  PubMed  CAS  Google Scholar 

  63. E.D. Kilbourne, B.E. Johansson, B. Grajower, Proc. Natl. Acad. Sci. USA 87, 786–790 (1990)

    Article  PubMed  CAS  Google Scholar 

  64. S. Bhatt, E.C. Holmes, O.G. Pybus, Mol. Biol. Evol. 28, 2443–2451 (2011)

    Article  PubMed  CAS  Google Scholar 

  65. M.J.Sylte, D.L.Suarez in R.W.Compans, W.A.Orenstein (eds.). (Springer, Berlin Heidelberg, 2009), pp. 227–241

  66. M. Fourment, J.T. Wood, A.J. Gibbs, M.J. Gibbs, Mol. Phylogenet. Evol. 56, 526–535 (2010)

    Article  PubMed  CAS  Google Scholar 

  67. S. Munier, T. Larcher, F. Cormier-Aline, D. Soubieux, B. Su, L. Guigand, B. Labrosse, Y. Cherel, P. Quere, D. Marc, N. Naffakh, J. Virol. 84, 940–952 (2010)

    Article  PubMed  CAS  Google Scholar 

  68. E.T. Munoz, M.W. Deem, Vaccine 23, 1144–1148 (2005)

    Article  PubMed  CAS  Google Scholar 

  69. N.J. McDonald, C.B. Smith, N.J. Cox, J. Gen. Virol. 88, 3209–3213 (2007)

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors are grateful to Hagag N. M., El-Husseiny M. H., Yehia N. from NLQP, Egypt and to Wessler D. and Illing C. FLI, Germany for their excellent technical support. Also, sincere gratitude is extended to three anonymous reviewers for their constructive comments and useful contributions that improved the manuscript. This work was supported by an OIE-funded twinning project between the National Laboratory for Quality Control on Production, Dokki, Giza, Egypt and Friedrich-Loeffler Institute, Isle of Riems, Germany and Institute of Poultry Diseases, Free University Berlin, Germany. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflict of interest

The authors declare that they have no conflict of interests.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to E. M. Abdelwhab.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Abdelwhab, E.M., Arafa, AS., Stech, J. et al. Diversifying evolution of highly pathogenic H5N1 avian influenza virus in Egypt from 2006 to 2011. Virus Genes 45, 14–23 (2012). https://doi.org/10.1007/s11262-012-0758-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11262-012-0758-1

Keywords

Navigation