Virologica Sinica

, Volume 26, Issue 6, pp 376–385 | Cite as

RETRACTED ARTICLE: Phylogenetic analysis of the non-structural (NS) gene of influenza a viruses isolated in Kazakhstan in 2002–2009

  • Andrey Bogoyavlenskiy
  • Vladimir Berezin
  • Alexey Prilipov
  • Ilya Korotetskiy
  • Irina Zaitseva
  • Aydyn Kydyrmanov
  • Kobey Karamedin
  • Nailya Ishmukhametova
  • Saule Asanova
  • Marat Sayatov
  • Kainar Zhumatov


Although the important role of the non-structural (NS1 and NEP) gene of influenza A in virulence of the virus is well established, our knowledge about the extent of variation in the NS gene pool of influenza A viruses in their natural reservoirs in Kazakhstan is incomplete. 17 influenza A viruses of different subtypes were studied in this paper. Seven types of haemagglutinin and five different neuraminidase subtypes in eight combinations were found among the isolated viruses. A comparison of nucleotide sequences of isolated viruses revealed a substantial number of silent mutations, which results in high degree of homology in amino acid sequences. By phylogenetic analysis it was shown that two distinct gene pools, corresponding to both NS allele A with 5 Clades and B, were present at the same time in Kazakhstan. The degree of variation within the alleles was very low. In our study allele A viruses had a maximum of 5% amino acid divergence in Clade while allele B viruses had only 4% amino acid divergence.

Key words

Influenza Nonstructural gene Phylogenetic analysis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Almond J W. 1977. A single gene determines the host range of influenza virus. Nature, 270:617–618.PubMedCrossRefGoogle Scholar
  2. 2.
    Bao Y P, Bolotov, Dernovoy D, et al. 2008. The Influenza Virus Resource at the National Center for Biotechnology Information J. Virol, 82(2):596–601.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Chen Z, Li Y, Krug R M. 1999. Influenza A virus NS1 protein targets poly(A)-binding protein II of the cellular 3′-end processing machinery. EMBO J, 18:2273–2283.PubMedCrossRefGoogle Scholar
  4. 4.
    European Union Council Directive 92/40/EEC of 19 May 1992 introducing Community measures for the control of avian influenza Official Journal L 167, 22/06/1992. 0001-0016.Google Scholar
  5. 5.
    Felsenstein J. 1985. Confidence limits on phylogenies: An approach using the bootstrap. Evolution, 39:783–791.CrossRefGoogle Scholar
  6. 6.
    Gagneux P, Cheriyan M, Hurtado-Ziola N}, et al. 2003. Human-specific regulation of alpha 2-6-linked sialic acids. J Biol Chem, 278:48245–48250.PubMedCrossRefGoogle Scholar
  7. 7.
    Hale B G, Randall R E, Ortın J, et al. 2008. The multifunctional NS1 protein of influenza A Viruses. J Gen Virol, 89: 2359–2376.PubMedCrossRefGoogle Scholar
  8. 8.
    Hatta M, Gao P, Halfmann P, et al. 2001. Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science, 293:1840–1842.PubMedCrossRefGoogle Scholar
  9. 9.
    Inglis S C, Barrett T, Brown C M, et al. 1979. The Smallest Genome RNA Segment of Influenza Virus Contains Two Genes that May Overlap. Proc Natl Acad Sci USA, 76:3790–3794.PubMedCrossRefGoogle Scholar
  10. 10.
    Kochs G, Garcia-Sastre A, Martinez-Sobrido L. 2007. Multiple AntiInterferon Actions of the Influenza A Virus NS1 Protein. J Virol, 81:7011–7021.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Kuiken T, Holmes E C, McCauley J, et al. 2006. Host species barriers to influenza virus infections. Science, 312:394–397.PubMedCrossRefGoogle Scholar
  12. 12.
    Krug R M, Yuan W, Noah D L, et al. 2003. Intracellular warfare between human influenza viruses and human cells: the roles of the viral NS1 protein. Virology, 309:181–189.PubMedCrossRefGoogle Scholar
  13. 13.
    Lamb R A, Choppin P W. 1979. Segment 8 of the Influenza Virus Genome is Unique in Coding for Two Polypeptides. Proc Natl Acad Sci USA, 76:4908–4912.PubMedCrossRefGoogle Scholar
  14. 14.
    Lamb R A, Lai C J. 1980. Sequence of interrupted and uninterrupted mRNAs and cloned DNA coding for the two overlapping nonstructural proteins of influenza virus. Cell, 21:475–485.PubMedCrossRefGoogle Scholar
  15. 15.
    Li Y, Chen Z Y, Wang W, et al. 2001. The 3′-end-processing factor CPSF is required for the splicing of single-intron pre-mRNAs in vivo. RNA, 7:920–931.PubMedCrossRefGoogle Scholar
  16. 16.
    Li Z, Jiang Y, Jiao P, et al. 2006. The NS1 Gene Contributes to the Virulence of H5N1 Avian Influenza Viruses. J Virol, 80:11115–11123.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Li S, Min J Y, Krug R M, et al. 2006. Binding of the influenza A virus NS1 protein to PKR mediates the inhibition of its activation by either PACT or double-stranded RNA. Virology, 349:13–21.PubMedCrossRefGoogle Scholar
  18. 18.
    Ludwig S, Schultz U, Mandler J, et al. 1991. Phylogenetic relationship of the nonstructural (NS) genes of influenza A viruses. Virology, 183:566–577.PubMedCrossRefGoogle Scholar
  19. 19.
    Matrosovich M, Tuzikov A, Bovin N, et al. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Mibayashi M, Martinez-Sobrido L, Loo Y M, et al. 2007. Inhibition of Retinoic Acid-Inducible Gene IMediated Induction of Beta Interferon by the NS1 Protein of Influenza A Virus. J Virol, 81:514–524.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Min J Y, Krug R M. 2006. The primary function of RNA binding by the influenza A virus NS1 protein in infected cells: Inhibiting the 2′-5′ oligo (A) synthetase/RNase L pathway. Proc Natl Acad Sci USA, 103:7100–7105.PubMedCrossRefGoogle Scholar
  22. 22.
    Nemeroff M E, Barabino S M L, Li Y, et al. 1998. Influenza Virus NS1 Protein Interacts with the Cellular 30 kDa Subunit of CPSF and Inhibits 3′ End Formation of Cellular PremRNAs. Mol Cell, 1:991–1000.PubMedCrossRefGoogle Scholar
  23. 23.
    Neumann G, Hughes M T, Yoshihiro K. 2000. Influenza A virus NS2 protein mediates vRNP nuclear export through NES-independent interaction with hCRM1. EMBO J, 19:6751–6758.PubMedCrossRefGoogle Scholar
  24. 24.
    Obenauer J C, Denson J, Mehta P K, et al. 2006. Large-Scale Sequence Analysis of Avian Influenza Isolates Science. 311:1576–1580.Google Scholar
  25. 25.
    Palese P, Shaw M L. 2007. Orthomyxoviridae: the viruses and their replication. In: Fields Virology, 5th edn, (D. M. Knipe & P. M. Howley.eds.). Philadelphia: Lippincott Williams & Wilkins. p1647–1689.Google Scholar
  26. 26.
    Qian X Y, Alonso-Caplen F, Krug R M. 1994. Two functional domains of the influenza virus NS1 protein are required for regulation of nuclear export of mRNA. J Virol, 68:2433–2411.PubMedCentralPubMedGoogle Scholar
  27. 27.
    Saitou N, Nei M. 1987. The neighbor-joining method: A new method for reconstructing phylogenetic trees. Mol Biol Evol. 4:406–425.PubMedGoogle Scholar
  28. 28.
    Shinya K, Ebina M, Yamada S, et al. 2006. Avian flu: influenza virus receptors in the human airway. Nature. 440:435–436.PubMedCrossRefGoogle Scholar
  29. 29.
    Spackman E, Slemons R D, Winker K, et al. 2005. Phylogenetic analyses of type A influenza genes in natural reservoir species in North America reveals genetic variation. Virus Res, 114:89–100.PubMedCrossRefGoogle Scholar
  30. 30.
    Suarez D L, Perdue M L. 1998. Multiple alignment comparison of the non-structural genes of influenza A viruses Virus Res. 54:59–69.PubMedCrossRefGoogle Scholar
  31. 31.
    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.PubMedCentralPubMedGoogle Scholar
  32. 32.
    Talon J, Horvath C M, Polley R, et al. 2000. Activation of interferon regulatory factor 3 is inhibited by the influenza A virus NS1 protein. J Virol, 74:7989–7996.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Tamura K, Dudley J, Nei M, et al. 2007. MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol. 24:1596–1599.PubMedCrossRefGoogle Scholar
  34. 34.
    Tamura K, Nei M, Kumar S. 2004. Prospects for inferring very large phylogenies by using the neighbor-joining method. Proc Natl Acad Sci USA, 101:11030–11035.PubMedCrossRefGoogle Scholar
  35. 35.
    Wang W, Riedel K, Lynch P, et al. 1999. RNA binding by the novel helical domain of the influenza virus NS1 protein requires its dimer structure and a small number of specific basic amino acids. RNA, 5:195–205.PubMedCrossRefGoogle Scholar
  36. 36.
    Yao Y, Mingay L J, McCauley J W, et al. 2001. Sequences in influenza A virus PB2 protein that determine productive infection for an avian influenza virus in mouse and human cell lines. J Virol, 75:5410–5415.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Zohari S, Gyarmati P, Ejdersund A, et al. 2008. Phylogenetic analysis of the non-structural (NS) gene of influenza A viruses isolated from mallards in Northern Europe in 2005 Virol J, 5:1–13.CrossRefGoogle Scholar

Copyright information

© Wuhan Institute of Virology, CAS and Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • Andrey Bogoyavlenskiy
    • 1
  • Vladimir Berezin
    • 1
  • Alexey Prilipov
    • 2
  • Ilya Korotetskiy
    • 1
  • Irina Zaitseva
    • 1
  • Aydyn Kydyrmanov
    • 1
  • Kobey Karamedin
    • 1
  • Nailya Ishmukhametova
    • 1
  • Saule Asanova
    • 1
  • Marat Sayatov
    • 1
  • Kainar Zhumatov
    • 1
  1. 1.Institute of Microbiology & VirologyAlmatyKazakhstan
  2. 2.Ivanovsky Institute of VirologyMoscowRussia

Personalised recommendations