Advertisement

Virus Genes

, Volume 54, Issue 3, pp 414–423 | Cite as

Differences in Type I interferon response in human lung epithelial cells infected by highly pathogenic H5N1 and low pathogenic H11N1 avian influenza viruses

  • Milind M. Thube
  • Pratip Shil
  • Rewati Kasbe
  • Avinash A. Patil
  • Shailesh D. Pawar
  • Jayati Mullick
Article

Abstract

Influenza A virus infection induces type I interferons (IFNs α/β) which activate host antiviral responses through a cascade of IFN signaling events. Herein, we compared highly pathogenic H5N1 and low pathogenic H11N1 avian influenza viruses isolated from India, for their replication kinetics and ability to induce IFN-β and interferon-stimulating genes (ISGs). The H5N1 virus showed a higher replication rate and induced less IFN-β and ISGs compared to the H11N1 virus when grown in the human lung epithelial A549 cells, reflecting the generation of differential innate immune responses during infection by these viruses. The non-structural 1 (NS1) protein, a major IFN-antagonist, known to help the virus in evading host innate immune response was compared from both the strains using bioinformatics tools. Analyses revealed differences in the composition of the NS1 proteins from the two strains that may have an impact on the modulation of the innate immune response. Intriguingly, H5N1 virus attenuated IFN-β response in a non-NS1 manner, suggesting the possible involvement of other viral proteins (PB2, PA, PB1/PB1-F2) of H5N1 in synergy with NS1. Preliminary analyses of the above proteins of the two strains by sequence comparison show differences in charged residues. The insight gained will be useful in designing experimental studies to elucidate a probable role of the polymerase protein(s) in association with NS1 in inhibiting the IFN signaling and understanding the molecular mechanism governing the difference.

Keywords

Influenza Avian influenza H5N1 H11N1 Interferon NS1 Innate immune response CPSF30 

Notes

Acknowledgements

We thank Ajit Rattan, Sachin Keng, Dinesh Singh, JPN Babu, SK Waghmare, AB Khare, and BSL3 staff for laboratory assistance, and P Aher, Drs. K Lole, P Yadav, and P Devhare for their help. We acknowledge the constant support of Dr. AC Mishra (Ex-Director) and Dr. DT Mourya, Director, NIV. We are grateful to Dr. Cecilia Dayaraj and Dr. Sarah Cherian for their critical comments. The work was supported by intramural funds from the Indian Council of Medical Research, New Delhi, India, and financial assistance to M. Thube from the Council of Scientific and Industrial Research, New Delhi, India and R. Kasbe from the University Grants Commission, New Delhi, India is gratefully acknowledged.

Author contributions

Conceived the idea and initiated the work: MMT & JM. Contributed to design of experiments: MMT, SDP, PS, & JM. Performed the experiments: MMT, RK, & PS (Bioinformatics). Contributed reagents/materials/analysis tools: JM, SDP, & PS. Analysis of experiments and results: MMT, PS, & JM. Contribution in generating graphics: MMT, RK, & AAP. Writing of the manuscript: MMT, PS, & JM. All the authors read and approved the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

This research work does not involve human participants and/or animals.

Informed consent

Not applicable as no human participants are involved.

Supplementary material

11262_2018_1556_MOESM1_ESM.eps (17 mb)
Supplementary material 1 (EPS 17422 kb)
11262_2018_1556_MOESM2_ESM.eps (1.3 mb)
Supplementary material 2 (EPS 1375 kb)
11262_2018_1556_MOESM3_ESM.eps (2.2 mb)
Supplementary material 3 (EPS 2291 kb)

References

  1. 1.
    P. Palese, M.L. Shaw, in Fields of Virology, ed. by D.M. Knipe, P.M. Howley (Lippincott Williams and Wilkins, Philadelphia, 2007), p. 1647Google Scholar
  2. 2.
    G. Neumann, Y. Kawaoka, Virology 479–480, 234–246 (2015)CrossRefPubMedGoogle Scholar
  3. 3.
    D.L. Suarez, in Avian Influenza, 1st edn., ed. by D.E. Swayne (Blackwell, Iowa, 2008), p. 3Google Scholar
  4. 4.
    J.S. Peiris, M.D. de Jong, Y. Guan, Clin. Microbiol. Rev. 20, 243–267 (2007)CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Z.M. Zhao, K.F. Shortridge, M. Garcia, Y. Guan, X.F. Wan, J. Gen. Virol. 89, 2182–2193 (2008)CrossRefPubMedGoogle Scholar
  6. 6.
    R.G. Webster, W.J. Bean, O.T. Gorman, T.M. Chambers, Y. Kawaoka, Microbiol. Rev. 56, 152–179 (1992)PubMedPubMedCentralGoogle Scholar
  7. 7.
    Y. Xu, A.M. Ramey, A.S. Bowman, T.J. DeLiberto, M.L. Killian, S. Krauss, J.M. Nolting, M.K. Torchetti, A.B. Reeves, R.J. Webby, D.E. Stallknecht, X.F. Wan, J. Virol. 91, e02208–e02216 (2017)PubMedPubMedCentralGoogle Scholar
  8. 8.
    X. Xu, K. Subbarao, N.J. Cox, Y. Guo, Virology 261, 15–19 (1999)CrossRefPubMedGoogle Scholar
  9. 9.
    M.L. Perdue, in Avian Influenza, ed. by D.E. Swayne (Blackwell, Iowa, 2008), p. 23CrossRefGoogle Scholar
  10. 10.
    K. Ray, V.A. Potdar, S.S. Cherian, S.D. Pawar, S.M. Jadhav, S.R. Waregaonkar, A.A. Joshi, A.C. Mishra, Virus Genes 36, 345–353 (2008)CrossRefPubMedGoogle Scholar
  11. 11.
    A.C. Mishra, S.S. Cherian, A.K. Chakrabarti, S.D. Pawar, S.M. Jadhav, B. Pal, S. Raut, S. Koratkar, S.S. Kode, Virol. J. 6, 26–34 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    A.K. Chakrabarti, S.D. Pawar, S.S. Cherian, S.S. Koratkar, S.M. Jadhav, B. Pal, S. Raut, V. Thite, S.S. Kode, S.S. Keng, B.J. Payyapilly, J. Mullick, A.C. Mishra, PLoS ONE 4, e7846 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    B. Opitz, A. Rejaibi, B. Dauber, J. Eckhard, M. Vinzing, B. Schmeck, S. Hippenstiel, N. Suttorp, T. Wolff, Cell. Microbiol. 9, 930–938 (2007)CrossRefPubMedGoogle Scholar
  14. 14.
    G.A. Versteeg, A. Garcia, in Viruses and Interferon Current Research, ed. by K. Mossman (Caister Academic Press, Norfolk, 2011), p. 181Google Scholar
  15. 15.
    D. Jia, R. Rahbar, R.W.Y. Chan, S.M.Y. Lee, M.C.W. Chan, B.X. Wang, D.P. Baker, B. Sun, J.S. Malik Peiris, J.M. Nicholls, E.N. Fish, PLoS ONE 5, e13927 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    B.G. Hale, R.E. Randall, J. Ortín, D. Jackson, J. Gen. Virol. 89, 2359–2376 (2008)CrossRefPubMedGoogle Scholar
  17. 17.
    A. García-Sastre, A. Egorov, D. Matassov, S. Brandt, D.E. Levy, J.E. Durbin, P. Palese, T. Muster, Virology 252, 324–330 (1998)CrossRefPubMedGoogle Scholar
  18. 18.
    S. Pawar, A. Chakrabarti, S. Cherian, S. Pande, M. Nanaware, S. Raut, B. Pal, S. Jadhav, S. Kode, S. Koratkar, V. Thite, A. Mishra, Virus Genes 41, 14–22 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    S.S. Koratkar, S.D. Pawar, V.N. Shelke, S.D. Kale, A.C. Mishra, Indian J. Med. Res. 139, 782–785 (2014)PubMedPubMedCentralGoogle Scholar
  20. 20.
    S. Mukherjee, S. Majumdar, V.C. Vipat, A.C. Mishra, A.K. Chakrabarti, Virol. J. 9, 149–160 (2012)CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    D.S. Tare, S.D. Pawar, J. Virol. Methods 224, 67–72 (2015)CrossRefPubMedGoogle Scholar
  22. 22.
    K.J. Livak, T.D. Schmittgen, Methods 25, 402–408 (2001)CrossRefPubMedGoogle Scholar
  23. 23.
    P. Shil, S.S. Chavan, S.S. Cherian, Bioinformation 7, 76–81 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    P. Shil, S. Chavan, S. Cherian, Bioinformation 6, 266–270 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    M. Matthaei, M. Budt, T. Wolff, PLoS ONE 8, e56659 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Z.T. Varga, A. Grant, B. Manicassamy, P. Palese, J. Virol. 86, 8359–8366 (2012)CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    M.J. Killip, E. Fodor, R.E. Randall, Virus Res. 209, 11–22 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    J.C.D. Long, E. Fodor, J. Virol. 90, 8729–8738 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    G. Kochs, A. Garcia-Sastre, L. Martinez-Sobrido, J. Virol. 81, 7011–7021 (2007)CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    I.-H. Kim, H.-J. Kwon, S.-H. Lee, D.-Y. Kim, J.-H. Kim, Vet. Microbiol. 175, 17–25 (2015)CrossRefPubMedGoogle Scholar
  31. 31.
    J.X. Long, D.X. Peng, Y.L. Liu, Y.T. Wu, X.F. Liu, Virus Genes 36, 471–478 (2008)CrossRefPubMedGoogle Scholar
  32. 32.
    B.G. Hale, J. Steel, R.A. Medina, B. Manicassamy, J. Ye, D. Hickman, R. Hai, M. Schmolke, A.C. Lowen, D.R. Perez, A. Garcia-Sastre, J. Virol. 84, 6909–6922 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    H. Zeng, C. Goldsmith, P. Thawatsupha, M. Chittaganpitch, S. Waicharoen, S. Zaki, T.M. Tumpey, J.M. Katz, J. Virol. 81, 12439–12449 (2007)CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    D. Goubau, R. Romieu-Mourez, M. Solis, E. Hernandez, T. Mesplède, R. Lin, D. Leaman, J. Hiscott, Eur. J. Immunol. 39, 527–540 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    D. Li, Z. Peng, H. Tang, P. Wei, X. Kong, D. Yan, F. Huang, Q. Li, X. Le, Q. Li, K. Xie, Clin. Cancer Res. 17, 3558–3568 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    P.B. Devhare, S.N. Chatterjee, V.A. Arankalle, K.S. Lole, PLoS ONE 8, e63793 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    CDC protocol of realtime RTPCR for influenza A viruses, http://www.who.int/csr/resources/publications/swineflu/realtimeptpcr/en/

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Avian Influenza Group, Microbial Containment ComplexICMR-National Institute of VirologyPuneIndia
  2. 2.Bioinformatics Laboratory, Microbial Containment ComplexICMR-National Institute of VirologyPuneIndia

Personalised recommendations