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Virulence of H5N1 avian influenza virus enhanced by a 15-nucleotide deletion in the viral nonstructural gene

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Abstract

More and more H5N1 subtype avian influenza viruses possessing a 15-nucleotide (15-nt) deletion in the viral nonstructural protein (NS) gene from position 263 to 277 have emerged since 2000. In order to investigate the biological significance of this deletion, two pairs of H5N1 reassortants designated as rWSN-SD versus rWSN-mSD and rWSN-YZ versus rWSN-mYZ were generated by reverse genetics technique. These recombinant viruses shared the same inner genes of PB1, PB2, PA, NP, and M from strain A/WSN/33(H1N1) and outer genes of HA and NA from strain A/Duck/Shandong/093/2004 (H5N1) (A/D/SD/04), whereas they bore different NS gene. Recombinant rWSN-SD carried the full sequence NS gene from A/D/SD/04 in the natural state without deletion, whereas rWSN-mSD carried the same NS gene, but with an artificial 15-nt deletion from position 263 to 277. On the other hand, rWSN-YZ contained the NS gene in the natural state with a deletion from A/Duck/Yangzhou/232/2004 (H5N1) (A/D/YZ/04), while rWSN-mYZ bore the same NS gene but with an artificial insertion of 15-nt in site 263–277. All the four reassortants grew well in embryonated chicken eggs with similar mean death time (MDT) and viral titer of EID50 or HA. However, the virulence of these reassortant viruses in chickens and mice was different. Reassortant viruses with deletion in their NS gene (rWSN-mSD and rWSN-YZ) had much higher intraveneous pathogenicity index (IVPI) in chickens and lower MLD50 in mice than their counterparts without the deletion (rWSN-SD and rWSN-mYZ). Furthermore, rWSN-mSD and rWSN-YZ caused significantly more deaths in infected chickens and higher virus titers in tissues of inoculated mice than did rWSN-SD and rWSN-mYZ respectively. Sequence analysis also showed that H5N1 viruses carrying the 15-nt deletion in the NS gene invariably had the D92E shift in their NS1 protein. The results indicated that the 15-nucleotide deletion of NS gene from site 263 to 277 associated with D92E shift in NS1 protein contributes to the virulence increase of H5N1 viruses in chickens and mice.

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References

  1. E.C. Claas, A.D. Osterhas, R. Van Beek, J.C. De Jong, G.F. Rimmelzwaan, D.A. Senne, S. Krauss, K.F. Shortridge, R.G. Webster, Lancet 351, 472–477 (1998)

    Article  CAS  Google Scholar 

  2. S.H. Seo, E. Hoffmann, R.G. Webster, Virus Res 103, 107–113 (2004)

    Article  CAS  Google Scholar 

  3. H.L. Chen, G.H. Deng, Z.J. Li, G.B. Tian, Y.B. Li, P.R. Jiao, L. Zhang, Z. Liu, R.G. Webster, K.Z. Yu, Proc Natl Acad Sci USA 101, 10452–10457 (2004)

    Article  CAS  Google Scholar 

  4. Z.J. Li, H.L. Chen, P.R. Jiao, G.H. Deng, G.B. Tian, Y.B. Li, E. Hoffmann, R.G. Webster, Y. Matsuoka, K. Yu, J Virol 79, 12058–12064 (2005)

    Article  CAS  Google Scholar 

  5. A.S. Lipatov, S. Andreansky, R.J. Webby, D.J. Hulse, J.E. Rehg, S. Krauss, D.R. Perez, P.C. Doherty, R.G. Webster, M.Y. Sangster, J Gen Virol 86, 1121–1130 (2005)

    Article  CAS  Google Scholar 

  6. S.H. Seo, E. Hoffmann, R.G. Webster, Nature Med 8, 950–954 (2002)

    Article  CAS  Google Scholar 

  7. Q. Zhu, H. Yang, W. Chen, W. Cao, G. Zhong, P. Jiao, G. Deng, K. Yu, C. Yang, Z. Bu, Y. Kawaoka, H. Chen, J Virol, Oct. 2007, 10, 1128/JVI, 00978-07

  8. K.S. Li, Y. Guan, J. Wang, G.J. Smith, K.M. Xu, L. Duan, A.P. Rahardjo, P. Puthavathana, C. Buranathai, T.D. Nguyen, A.T. Estoepangestie, A. Chaisingh, P. Auewarakul, H.T. Long, N.T. Hanh, R.G. Webby, L.L. Poon, H.L. Chen, K.F. Shortridge, K.Y. Yuen, R.G. Webster, J.S. Peiris, Natrue 430, 209–212 (2004)

    Article  CAS  Google Scholar 

  9. Y. Guan, L.L.M. Poon, C.Y. Cheung, T.M. Ellis, W. Lim, A.S. Lipatov, K.H. Chan, K.M. Sturm-Ramirez, C.L. Cheung, Y.H.C. Leung, K.Y. Yuen, R.G. Webster, J.S.M. Peiris, Proc Natl Acad Sci USA 101, 8156–8161 (2004)

    Article  CAS  Google Scholar 

  10. H.B. Zhou, M.L. Jin, H.C. Chen, Q.F. Huang, Z.J. Yu, Virus Genes 32, 85–95 (2006)

    Article  CAS  Google Scholar 

  11. Anonymous, OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2004 (http://www.oie.int/eng/normes/mmanual/), chapter 2.7.12

  12. E. Hoffmann, N.N. Zhou, R.G. Webster, Inte Congr Ser 1219, 1007–1013 (2001)

    Article  CAS  Google Scholar 

  13. E. Hoffmann, J. Stech, Y. Guan, R.G. Webster, D.R. Perez, Arch Virol 146, 2275–2289 (2001)

    Article  CAS  Google Scholar 

  14. G. Neumann, Y. Kawaoka, Virology 287, 243–250 (2001)

    Article  CAS  Google Scholar 

  15. E. Hoffmann, G. Neumann, Y. Kawaoka, G. Hobom, R.G. Webster, Proc Natl Acad Sci USA 97, 6108–6113 (2000)

    Article  CAS  Google Scholar 

  16. E. Hoffmann, S. Krauss, D. Perez, R. Webby, R.G. Webster, Vaccine 20, 3165–3170 (2002)

    Article  CAS  Google Scholar 

  17. K. Subbarao, H.L. Chen, D. Swayne, L. Mingay, E. Fodor, G. Brownlee, X. Xu, X. Lu, J. Katz, N. Cox, Y. Matsuoka, Virology 305, 192–200 (2003)

    Article  CAS  Google Scholar 

  18. L.J. Reed, H. Muench, Am J Hyg 27, 493–497 (1938)

    Google Scholar 

  19. K. Shinya, M. Ebina, Y. Shinya, M. Ono, N. Kasai, Y. Kawaoka, Natrue 440, 435–436 (2006)

    Article  CAS  Google Scholar 

  20. N. Dennis, Science 311, 1692 (2006)

    Google Scholar 

  21. D.V. Riel, V.J. Munster, E. Wit, G.F. Rimmelzwaan, R.A.M. Fouchier, A.D.M.E. Osterhaus, T. Kuiken, Science 312, 399 (2006)

    Article  Google Scholar 

  22. S.H. Seo, R.G. Webster, J Virol 76, 1071–1076 (2002)

    Article  CAS  Google Scholar 

  23. N.R. Donelan, C.F. Basler, G.S. Adolfo, J Virol 77, 13257–13266 (2003)

    Article  CAS  Google Scholar 

  24. M.R. Castrucci, Y. Kawaoka, J Virol 67, 759–764 (1993)

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Key Technologies R&D Program of China (2006BAD06A01), the Major Basic Research Project for Provincial University and college of Jiangsu Province (05KJA23016) and the National High-Tech Research and Development Program of China (863 Program 2006AA10A205).

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  1. Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, P.R. China

    Jin-Xue Long, Da-Xin Peng, Yu-Liang Liu, Yan-Tao Wu & Xiu-Fan Liu

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  1. Jin-Xue Long
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  2. Da-Xin Peng
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  3. Yu-Liang Liu
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  4. Yan-Tao Wu
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Correspondence to Xiu-Fan Liu.

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Long, JX., Peng, DX., Liu, YL. et al. Virulence of H5N1 avian influenza virus enhanced by a 15-nucleotide deletion in the viral nonstructural gene. Virus Genes 36, 471–478 (2008). https://doi.org/10.1007/s11262-007-0187-8

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  • DOI: https://doi.org/10.1007/s11262-007-0187-8

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