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Mini-Review · 8 December 2014 · Open Access

Biological Relevance of C-terminal Elongation of the NS1 Protein of Influenza A Viruses

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Affiliations & Notes ⌄
  1. 1Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agri- cultural University, Beijing 100193, China
  2. 2China Rural Technology Development Center, Beijing, 100045, China
Article Info ⌄
Journal:
Hosts and Viruses
Published:
8 December 2014
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From the article

  • Biological Relevance of C-terminal Elongation of the NS1 Protein of Influenza A Viruses.
  • These findings suggested that the C-terminal tail of the NS1 protein modulates the viral virulence of classical H1N1 swine influenza virus to some extent.
  • A new influenza virus virulence determinant: the NS1 protein four C-terminal residues modulate pathogencity.
  • The PDZ-binding motif of the avian NS1 protein affects transmission of the 2009 influenza A (H1N1) virus.

Selected from the article's own text.

Abstract

The non-structural 1 (NS1) protein plays a crucial role in moderating the virulence of influenza virus by multiple mechanisms. Due to C-terminal ‘tail’ (CTT) truncation of NS1, there are length variation types of NS1 in different subtype influenza viruses. CTT functions in several ways to defeat the cellular innate immune responses. Here, we discuss those different effects of CTT truncation or elongation of NS1 protein in different genetic backgrounds of influenza experimentations. Conclusively, it can be stated that CTT confers a positive role during the infection of influenza A viruses. However, this regulation is contributed by multiple factors and has variable impact on the pathobiology of influenza A viruses.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (no. 31172323 and no. 31172324).

References

  1. • Dundon WG. Variability among the neuraminidase, non-structural 1 and PB1-F2 proteins in the influenza A virus genome. Virus Genes. 2012; 44(3): 363-73.
  2. • Dundon WG, Capua I. A closer look at the NS1 of influenza virus. Viruses. 2009; 1, 1057-1072.
  3. • Golebiewski L, Liu H, Javier RT, Rice AP. The avian influenza virus NS1 ESEV PDZ binding motif associates with Dlg1 and Scribble to disrupt cellular tight junctions. Journal of Virology. 2011; 85(20):10639-48.
  4. • Hale BG. Conformational plasticity of the influenza A virus NS1 protein. Journal of General Virology. 2014; 95:2099-105.
  5. • Hale BG, Steel J, Manicassamy B, Medina RA, Ye J, Hickman D, Lowen AC, Perez DR, García-Sastre A. Mutations in the NS1 C-terminal tail do not enhance replication or virulence of the 2009 pandemic H1N1 influenzaA virus. Journal of General Virology. 2010; 91:1737-1742.
  6. • Heikkinen LS, Kazlauskas A, Melén K, Wagner R, Ziegler T, Julkunen I, Saksela K. Avian and 1918 Spanish influenza a virus NS1 proteins bind to Crk/CrkL Src homology 3 domains to activate host cell signaling. Journal of Biological Chemistry. 2008; 283(9):5719-27.
  7. • Jackson D, Hossain MJ, Hickman D, Perez DR, Lamb RA. A new influenza virus virulence determinant: the NS1 protein four C-terminal residues modulate pathogencity. Proceedings of the National Academy of Sciences USA. 2008; 105(11): 4381-6.
  8. • Kim JI, Hwang MW, Lee I, Park S, Lee S, Bae JY, Heo J, Kim D, Jang SI, Park MS, Kwon HJ, Song JW, Park MS. The PDZ-binding motif of the avian NS1 protein affects transmission of the 2009 influenza A (H1N1) virus. Biochemical and Biophysical Research Communications. 2014; 449, 19-25.
  9. • Kong W, Liu L, Wang Y, He Q, Wu S, Qin Z, Wang J, Sun H, Sun Y, Zhang R, Pu J, Liu J. The C-terminal elongation of NS1 of H9N2 influenza virus induces a high level of inflammatory cytokines and increases transmission. Journal of General Virology. 2014 Oct 17. doi: 10.1099/vir.0.071001-0.[CrossRef]
  10. • Kumar M, Liu H, Rice AP. Regulation of interferon-beta by MAGI-1 and its interaction with influenza A virus NS1 protein with ESEV PBM. PLoS One. 2012; 7(7):e41251.
  11. • Laura Bavagnoli, William G. Dundon, Anna Garbelli, Bianca Zecchin, Adelaide Milani, Geetha Parakkal, Fausto Baldanti, Stefania Paolucci, Romain Volmer, Yizeng Tu, Chuanyue Wu, Ilaria Capua, Giovanni Maga. The PDZ-Ligand and Src-Homology Type 3 Domains of Epidemic Avian Influenza Virus NS1 Protein Modulate Human Src Kinase Activity during Viral Infection. PLoS One. 2011; 6(11): e27789.
  12. • Liu H, Golebiewski L, Dow EC, Krug RM, Javier RT, Rice AP. The ESEV PDZ-binding motif of the avian influenza A virus NS1 protein protects infected cells from apoptosis by directly targeting Scribble. Journal of Virology. 2010; 84(21): 11164-74.
  13. • Lohrmann F, Dijkman R, Stertz S, Thiel V, Haller O, Staeheli P, Kochs G. Emergence of a C-terminal seven-amino-acid elongation of NS1 in around 1950 conferred a minor growth advantage to former seasonal influenza A viruses. Journal of Virology. 2013; 87(20): 11300-3.
  14. • Marazzi I, Ho JS, Kim J, Manicassamy B, Dewell S, Albrecht RA, Seibert CW, Schaefer U, Jeffrey KL, Prinjha RK, Lee K, García-Sastre A, Roeder RG, Tarakhovsky A. Suppression of the antiviral response by an influenza histone mimic. Nature. 2012 14; 483(7390):428-33.
  15. • Munir M, Zohari S, Berg M. Non-structural protein 1 of avian influenza A viruses differentially inhibit NF-kB promoter activation. Virology Journal. 2011a Aug 2;8:383.
  16. • Munir M, Zohari S, Metreveli G, Baule C, Belák S, Berg M. Alleles A and B of non-structural protein 1 of avian influenza A viruses differentially inhibit beta interferon production in human and mink lung cells. Journal of General Virology. 2011b; 92(9):2111-21.
  17. • Ozawa M, Basnet S, Burley LM, Neumann G, Hatta M, Kawaoka Y. Impact of amino acid mutations in PB2, PB1-F2, and NS1 on the replication and pathogenicity of pandemic (H1N1) 2009 influenza viruses. Journal of Virology. 2011; 85(9): 4596-601.
  18. • Satterly N, Tsai PL, van Deursen J, Nussenzveig DR, Wang Y, Faria PA, Levay A, Levy DE, Fontoura BM. Influenza virus targets the mRNA export machinery and the nuclear pore complex. Proceedings of the National Academy of Sciences USA. 2007; 104(6):1853-8.
  19. • Soubies SM, Hoffmann TW, Croville G, Larcher T, Ledevin M, Soubieux D, Quéré P, Guérin JL, Marc D, Volmer R. Deletion of the C-terminal ESEV domain of NS1 does not affect the replication of a low-pathogenic avian influenza virus H7N1 in ducks and chickens. Journal of General Virology. 2013; 94:50-8.
  20. • Soubies SM, Volmer C, Croville G, Loupias J, Peralta B, Costes P, Lacroux C, Guérin JL, Volmer R. Species-specific contribution of the four C-terminal amino acids of influenza A virus NS1 protein to virulence. Journal of Virology. 2010; 84(13): 6733-47.
  21. • Tong S, Zhu X, Li Y, Shi M, Zhang J, Bourgeois M, Yang H, Chen X, Recuenco S, Gomez J, Chen LM, Johnson A, Tao Y, Dreyfus C, Yu W, McBride R, Carney PJ, Gilbert AT, Chang J, Guo Z, Davis CT, Paulson JC, Stevens J, Rupprecht CE, Holmes EC, Wilson IA, Donis RO. New world bats harbor diverse influenza A viruses. PLoS Pathogen. 2013; 9(10):e1003657.
  22. • Wang J, Qi X, Lu C. Mutations in the C-terminal tail of NS1 protein facilitate the replication of classical swine H1N1 influenza A virus in mice. Folia Microbiol (Praha). 2012; 57(3): 169-75.
  23. • Yu J, Li X, Wang Y, Li B, Li H, Li Y, Zhou W, Zhang C, Wang Y, Rao Z, Bartlam M, Cao Y. PDlim2 selectively interacts with the PDZ binding motif of highly pathogenic avian H5N1 influenza A virus NS1. PLoS One. 2011; 6(5): e19511.
  24. • Zielecki F, Semmler I, Kalthoff D, Voss D, Mauel S, Gruber AD, Beer M, Wolff T. Virulence determinants of avian H5N1 influenza A virus in mammalian and avian hosts: role of the C-terminal ESEV motif in the viral NS1 protein. Journal of Virology. 2010; 84(20): 10708-18.

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