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Activation of NF-κB by nucleocapsid protein of the porcine reproductive and respiratory syndrome virus

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Abstract

Nuclear factor kappa B (NF-κB) is a critical transcription factor in innate and adaptive immune response as well as cell proliferation and survival. Previous studies have demonstrated that porcine reproductive and respiratory syndrome virus (PRRSV) infection activated NF-κB pathways through IκB degradation in MARC-145 cells and alveolar macrophages. To evaluate the mechanisms behind this, we investigated the role of PRRSV structural proteins in the regulation of NF-κB. In this study, we screened the structural proteins of PRRSV by NF-κB DNA-binding assay and luciferase activity assay and demonstrated that PRRSV nucleocapsid (N) protein could activate NF-κB in MARC-145 cells. Furthermore, we revealed that the region between aa 30 and 73 of N protein was essential for its function in the activation of NF-κB. These results presented here provide a basis for understanding molecular mechanism of PRRSV infection and inflammation response.

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References

  1. E.J. Neumann, J.B. Kliebenstein, C.D. Johnson, J.W. Mabry, E.J. Bush, A.H. Seitzinger, A.L. Green, J.J. Zimmerman, Assessment of the economic impact of porcine reproductive and respiratory syndrome on swine production in the United States. J. Am. Vet. Med. Assoc. 227, 385–392 (2005)

    Article  PubMed  Google Scholar 

  2. S. Dea, C.A. Gagnon, H. Mardassi, B. Pirzadeh, D. Rogan, Current knowledge on the structural proteins of porcine reproductive and respiratory syndrome (PRRS) virus: comparison of the North American and European isolates. Arch. Virol. 145, 659–688 (2000)

    Article  PubMed  CAS  Google Scholar 

  3. E.J. Snijder, J.J. Meulenberg, The molecular biology of arteriviruses. J. Gen. Virol. 79, 961–979 (1998)

    PubMed  CAS  Google Scholar 

  4. S. Wootton, D. Yoo, D. Rogan, Full-length sequence of a Canadian porcine reproductive and respiratory syndrome virus (PRRSV) isolate. Arch. Virol. 145, 2297–2323 (2000)

    Article  PubMed  CAS  Google Scholar 

  5. M. Karin, Y. Cao, F.R. Greten, Z.W. Li, NF-kappaB in cancer: from innocent bystander to major culprit. Nat. Rev. Cancer 2, 301–310 (2002)

    Article  PubMed  CAS  Google Scholar 

  6. Q. Li, I.M. Verma, NF-kappaB regulation in the immune system. Nat. Rev. Immunol. 2, 725–734 (2002)

    Article  PubMed  CAS  Google Scholar 

  7. A.A. Beg, A.S. Baldwin, The I kappa B proteins: multifunctional regulators of Rel/NF-kappa B transcription factors. Genes Dev. 7, 2064–2070 (1993)

    Article  PubMed  CAS  Google Scholar 

  8. M.S. Hayden, S. Ghosh, Signaling to NF-kappaB. Genes Dev. 18, 2195–2224 (2004)

    Article  PubMed  CAS  Google Scholar 

  9. G. Mosialos, M. Birkenbach, R. Yalamanchili, T. VanArsdale, C. Ware, E. Kieff, The Epstein–Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family. Cell 80, 389–399 (1995)

    Article  PubMed  CAS  Google Scholar 

  10. Z.L. Chu, J.A. DiDonato, J. Hawiger, D.W. Ballard, The tax oncoprotein of human T-cell leukemia virus type 1 associates with and persistently activates IkappaB kinases containing IKKalpha and IKKbeta. J. Biol. Chem. 273, 15891–15894 (1998)

    Article  PubMed  CAS  Google Scholar 

  11. L.R. You, C.M. Chen, Y.H. Lee, Hepatitis C virus core protein enhances NF-kappaB signal pathway triggering by lymphotoxin-beta receptor ligand and tumor necrosis factor alpha. J. Virol. 73, 1672–1681 (1999)

    PubMed  CAS  Google Scholar 

  12. S.M. Lee, S.B. Kleiboeker, Porcine arterivirus activates the NF-kappaB pathway through IkappaB degradation. Virology 342, 47–59 (2005)

    Article  PubMed  CAS  Google Scholar 

  13. R. Luo, S. Xiao, Y. Jiang, H. Jin, D. Wang, M. Liu, H. Chen, L. Fang, Porcine reproductive and respiratory syndrome virus (PRRSV) suppresses interferon-beta production by interfering with the RIG-I signaling pathway. Mol. Immunol. 45, 2839–2846 (2008)

    Article  PubMed  CAS  Google Scholar 

  14. S.K. Wootton, E.A. Nelson, D. Yoo, Antigenic structure of the nucleocapsid protein of porcine reproductive and respiratory syndrome virus. Clin. Diagn. Lab. Immunol. 5, 773–779 (1998)

    PubMed  CAS  Google Scholar 

  15. S.K. Wootton, D. Yoo, Homo-oligomerization of the porcine reproductive and respiratory syndrome virus nucleocapsid protein and the role of disulfide linkages. J. Virol. 77, 4546–4557 (2003)

    Article  PubMed  CAS  Google Scholar 

  16. T. Ait-Ali, A.D. Wilson, D.G. Westcott, M. Clapperton, M. Waterfall, M.A. Mellencamp, T.W. Drew, S.C. Bishop, A.L. Archibald, Innate immune responses to replication of porcine reproductive and respiratory syndrome virus in isolated Swine alveolar macrophages. Viral Immunol. 20, 105–118 (2007)

    Article  PubMed  CAS  Google Scholar 

  17. E. Mateu, I. Diaz, The challenge of PRRS immunology. Vet. J. 177, 345–351 (2008)

    Article  PubMed  CAS  Google Scholar 

  18. J.W. Christman, R.T. Sadikot, T.S. Blackwell, The role of nuclear factor-kappa B in pulmonary diseases. Chest 117, 1482–1487 (2000)

    Article  PubMed  CAS  Google Scholar 

  19. J.G. Mastronarde, B. He, M.M. Monick, N. Mukaida, K. Matsushima, G.W. Hunninghake, Induction of interleukin (IL)-8 gene expression by respiratory syncytial virus involves activation of nuclear factor (NF)-kappa B and NF-IL-6. J. Infect. Dis. 174, 262–267 (1996)

    Article  PubMed  CAS  Google Scholar 

  20. L.H. Thomas, J.S. Friedland, M. Sharland, S. Becker, Respiratory syncytial virus-induced RANTES production from human bronchial epithelial cells is dependent on nuclear factor-kappa B nuclear binding and is inhibited by adenovirus-mediated expression of inhibitor of kappa B alpha. J. Immunol. 161, 1007–1016 (1998)

    PubMed  CAS  Google Scholar 

  21. R.R. Rowland, P. Schneider, Y. Fang, S. Wootton, D. Yoo, D.A. Benfield, Peptide domains involved in the localization of the porcine reproductive and respiratory syndrome virus nucleocapsid protein to the nucleolus. Virology 316, 135–145 (2003)

    Article  PubMed  CAS  Google Scholar 

  22. R.R. Rowland, D. Yoo, Nucleolar-cytoplasmic shuttling of PRRSV nucleocapsid protein: a simple case of molecular mimicry or the complex regulation by nuclear import, nucleolar localization and nuclear export signal sequences. Virus Res. 95, 23–33 (2003)

    Article  PubMed  CAS  Google Scholar 

  23. J.H. You, G. Howell, A.K. Pattnaik, F.A. Osorio, J.A. Hiscox, A model for the dynamic nuclear/nucleolar/cytoplasmic trafficking of the porcine reproductive and respiratory syndrome virus (PRRSV) nucleocapsid protein based on live cell imaging. Virology 378, 34–47 (2008)

    Article  PubMed  CAS  Google Scholar 

  24. Y. Pei, D.C. Hodgins, C. Lee, J.G. Calvert, S.K. Welch, R. Jolie, M. Keith, D. Yoo, Functional mapping of the porcine reproductive and respiratory syndrome virus capsid protein nuclear localization signal and its pathogenic association. Virus Res. 135, 107–114 (2008)

    Article  PubMed  CAS  Google Scholar 

  25. M. Karin, A. Lin, NF-kappaB at the crossroads of life and death. Nat. Immunol. 3, 221–227 (2002)

    Article  PubMed  CAS  Google Scholar 

  26. X. Liu, K. Fitzgerald, E. Kurt-Jones, R. Finberg, D.M. Knipe, Herpesvirus tegument protein activates NF-kappaB signaling through the TRAF6 adaptor protein. Proc. Natl Acad. Sci. USA 105, 11335–11339 (2008)

    Article  PubMed  CAS  Google Scholar 

  27. K. Watashi, M. Hijikata, H. Marusawa, T. Doi, K. Shimotohno, Cytoplasmic localization is important for transcription factor nuclear factor-kappa B activation by hepatitis C virus core protein through its amino terminal region. Virology 286, 391–402 (2001)

    Article  PubMed  CAS  Google Scholar 

  28. M. Luftig, T. Yasui, V. Soni, M.S. Kang, N. Jacobson, E. Cahir-McFarland, B. Seed, E. Kieff, Epstein-Barr virus latent infection membrane protein 1 TRAF-binding site induces NIK/IKK alpha-dependent noncanonical NF-kappaB activation. Proc. Natl Acad. Sci. USA 101, 141–146 (2004)

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Sciences Foundation of China (31001054, 30800046) and the New Century Excellent Talent Project (NCET-07-0347).

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Correspondence to Shaobo Xiao.

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Luo, R., Fang, L., Jiang, Y. et al. Activation of NF-κB by nucleocapsid protein of the porcine reproductive and respiratory syndrome virus. Virus Genes 42, 76–81 (2011). https://doi.org/10.1007/s11262-010-0548-6

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  • DOI: https://doi.org/10.1007/s11262-010-0548-6

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