1887

Abstract

Newcastle disease virus (NDV) causes a severe and economically significant disease affecting almost the entire poultry industry worldwide. However, factors that affect NDV replication in host cells are poorly understood. Raf kinase inhibitory protein (RKIP) is a physiological inhibitor of c-RAF kinase and NF-κB signalling, known for their functions in the control of immune response as well as tumour invasion and metastasis. In the present study, we investigated the consequences of overexpression of host RKIP during viral infection. We demonstrate that NDV infection represses RKIP expression thereby promoting virus replication. Experimental upregulation of RKIP in turn acts as a potential antiviral defence mechanism in host cells that restricts NDV replication by repressing the activation of Raf/MEK/ERK and IκBα/NF-κB signalling pathways. Our results not only extend the concept of linking NDV–host interactions, but also reveal RKIP as a new class of protein-kinase-inhibitor protein that affects NDV replication with therapeutic potential.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000228
2015-09-01
2019-12-13
Loading full text...

Full text loading...

/deliver/fulltext/jgv/96/9/2579.html?itemId=/content/journal/jgv/10.1099/jgv.0.000228&mimeType=html&fmt=ahah

References

  1. Amaya M. , Voss K. , Sampey G. , Senina S. , de la Fuente C. , Mueller C. , Calvert V. , Kehn-Hall K. , Carpenter C. , other authors . ( 2014;). The role of IKKβ in Venezuelan equine encephalitis virus infection. PLoS One 9: e86745 [CrossRef] [PubMed].
    [Google Scholar]
  2. Antoun G. , Bouchard-Cannon P. , Cheng H.Y.M. . ( 2012;). Regulation of MAPK/ERK signaling and photic entrainment of the suprachiasmatic nucleus circadian clock by Raf kinase inhibitor protein. J Neurosci 32: 4867–4877 [CrossRef] [PubMed].
    [Google Scholar]
  3. Beshir A.B. , Ren G. , Magpusao A.N. , Barone L.M. , Yeung K.C. , Fenteany G. . ( 2010;). Raf kinase inhibitor protein suppresses nuclear factor-κB-dependent cancer cell invasion through negative regulation of matrix metalloproteinase expression. Cancer Lett 299: 137–149 [CrossRef] [PubMed].
    [Google Scholar]
  4. Cantrell S.R. , Bresnahan W.A. . ( 2005;). Interaction between the human cytomegalovirus UL82 gene product (pp71) and hDaxx regulates immediate-early gene expression and viral replication. J Virol 79: 7792–7802 [CrossRef] [PubMed].
    [Google Scholar]
  5. Cheng J. , Sun Y. , Zhang X. , Zhang F. , Zhang S. , Yu S. , Qiu X. , Tan L. , Song C. , other authors . ( 2014;). Toll-like receptor 3 inhibits Newcastle disease virus replication through activation of pro-inflammatory cytokines and the type-1 interferon pathway. Arch Virol 159: 2937–2948 [CrossRef] [PubMed].
    [Google Scholar]
  6. de Leeuw O. , Peeters B. . ( 1999;). Complete nucleotide sequence of Newcastle disease virus: evidence for the existence of a new genus within the subfamily Paramyxovirinae . J Gen Virol 80: 131–136 [PubMed].[CrossRef]
    [Google Scholar]
  7. de Leeuw O.S. , Koch G. , Hartog L. , Ravenshorst N. , Peeters B.P. . ( 2005;). Virulence of Newcastle disease virus is determined by the cleavage site of the fusion protein and by both the stem region and globular head of the haemagglutinin-neuraminidase protein. J Gen Virol 86: 1759–1769 [CrossRef] [PubMed].
    [Google Scholar]
  8. Dortmans J.C. , Rottier P.J. , Koch G. , Peeters B.P. . ( 2010;). The viral replication complex is associated with the virulence of Newcastle disease virus. J Virol 84: 10113–10120 [CrossRef] [PubMed].
    [Google Scholar]
  9. Dortmans J.C. , Koch G. , Rottier P.J. , Peeters B.P. . ( 2011;). Virulence of Newcastle disease virus: what is known so far?. Vet Res 42: 122 [CrossRef] [PubMed].
    [Google Scholar]
  10. Ford P.W. , Bryan B.A. , Dyson O.F. , Weidner D.A. , Chintalgattu V. , Akula S.M. . ( 2006;). Raf/MEK/ERK signalling triggers reactivation of Kaposi's sarcoma-associated herpesvirus latency. J Gen Virol 87: 1139–1144 [CrossRef] [PubMed].
    [Google Scholar]
  11. Goodman A.G. , Tanner B.C. , Chang S.T. , Esteban M. , Katze M.G. . ( 2011;). Virus infection rapidly activates the P58(IPK) pathway, delaying peak kinase activation to enhance viral replication. Virology 417: 27–36 [CrossRef] [PubMed].
    [Google Scholar]
  12. Hiscott J. , Kwon H. , Génin P. . ( 2001;). Hostile takeovers: viral appropriation of the NF-κB pathway. J Clin Invest 107: 143–151 [CrossRef] [PubMed].
    [Google Scholar]
  13. Johnson G.L. , Stuhlmiller T.J. , Angus S.P. , Zawistowski J.S. , Graves L.M. . ( 2014;). Molecular pathways: adaptive kinome reprogramming in response to targeted inhibition of the BRAF-MEK-ERK pathway in cancer. Clin Cancer Res 20: 2516–2522 [CrossRef] [PubMed].
    [Google Scholar]
  14. Kim Y.S. , Kim J.S. , Kwon J.S. , Jeong M.H. , Cho J.G. , Park J.C. , Kang J.C. , Ahn Y. . ( 2010;). BAY 11-7082, a nuclear factor-κB inhibitor, reduces inflammation and apoptosis in a rat cardiac ischemia-reperfusion injury model. Int Heart J 51: 348–353 [CrossRef] [PubMed].
    [Google Scholar]
  15. Krishnamurthy S. , Takimoto T. , Scroggs R.A. , Portner A. . ( 2006;). Differentially regulated interferon response determines the outcome of Newcastle disease virus infection in normal and tumor cell lines. J Virol 80: 5145–5155 [CrossRef] [PubMed].
    [Google Scholar]
  16. Liu N. , Long Y. , Liu B. , Yang D. , Li C. , Chen T. , Wang X. , Liu C. , Zhu H. . ( 2014;). ISG12a mediates cell response to Newcastle disease viral infection. Virology 462-463: 283–294 [CrossRef] [PubMed].
    [Google Scholar]
  17. Lopez-Ilasaca M. , Crespo P. , Pellici P.G. , Gutkind J.S. , Wetzker R. . ( 1997;). Linkage of G protein-coupled receptors to the MAPK signaling pathway through PI 3-kinase gamma. Science 275: 394–397 [CrossRef] [PubMed].
    [Google Scholar]
  18. Mathers C. , Schafer X. , Martínez-Sobrido L. , Munger J. . ( 2014;). The human cytomegalovirus UL26 protein antagonizes NF-κB activation. J Virol 88: 14289–14300 [CrossRef] [PubMed].
    [Google Scholar]
  19. Mazur I. , Wurzer W.J. , Ehrhardt C. , Pleschka S. , Puthavathana P. , Silberzahn T. , Wolff T. , Planz O. , Ludwig S. . ( 2007;). Acetylsalicylic acid (ASA) blocks influenza virus propagation via its NF-κB-inhibiting activity. Cell Microbiol 9: 1683–1694 [CrossRef] [PubMed].
    [Google Scholar]
  20. Meng G. , Xia M. , Wang D. , Chen A. , Wang Y. , Wang H. , Yu D. , Wei J. . ( 2014;). Mitophagy promotes replication of oncolytic Newcastle disease virus by blocking intrinsic apoptosis in lung cancer cells. Oncotarget 5: 6365–6374 [PubMed].[CrossRef]
    [Google Scholar]
  21. Mostafa H.H. , Thompson T.W. , Davido D.J. . ( 2013;). N-terminal phosphorylation sites of herpes simplex virus 1 ICP0 differentially regulate its activities and enhance viral replication. J Virol 87: 2109–2119 [CrossRef] [PubMed].
    [Google Scholar]
  22. Ng S.S. , Li A. , Pavlakis G.N. , Ozato K. , Kino T. . ( 2013;). Viral infection increases glucocorticoid-induced interleukin-10 production through ERK-mediated phosphorylation of the glucocorticoid receptor in dendritic cells: potential clinical implications. PLoS One 8: e63587 [CrossRef] [PubMed].
    [Google Scholar]
  23. Ong Q. , Guo S. , Zhang K. , Cui B. . ( 2015;). U0126 protects cells against oxidative stress independent of its function as a MEK inhibitor. ACS Chem Neurosci 6: 130–137 [CrossRef] [PubMed].
    [Google Scholar]
  24. Paulmann D. , Bortmann S. , Grimm F. , Berk I. , Kraemer L. , Vallbracht A. , Dotzauer A. . ( 2014;). NF-κB activation induced by hepatitis A virus and Newcastle disease virus occurs by different pathways depending on the structural pattern of viral nucleic acids. Arch Virol 159: 1723–1733 [CrossRef] [PubMed].
    [Google Scholar]
  25. Pinto R. , Herold S. , Cakarova L. , Hoegner K. , Lohmeyer J. , Planz O. , Pleschka S. . ( 2011;). Inhibition of influenza virus-induced NF-κB and Raf/MEK/ERK activation can reduce both virus titers and cytokine expression simultaneously in vitro and in vivo. Antiviral Res 92: 45–56 [CrossRef] [PubMed].
    [Google Scholar]
  26. Puhlmann J. , Puehler F. , Mumberg D. , Boukamp P. , Beier R. . ( 2010;). Rac1 is required for oncolytic NDV replication in human cancer cells and establishes a link between tumorigenesis and sensitivity to oncolytic virus. Oncogene 29: 2205–2216 [CrossRef] [PubMed].
    [Google Scholar]
  27. Saribas A.S. , Mun S. , Johnson J. , El-Hajmoussa M. , White M.K. , Safak M. . ( 2014;). Human polyoma JC virus minor capsid proteins, VP2 and VP3, enhance large T antigen binding to the origin of viral DNA replication: evidence for their involvement in regulation of the viral DNA replication. Virology 449: 1–16 [CrossRef] [PubMed].
    [Google Scholar]
  28. Sisto M. , Lisi S. , D'Amore M. , Lofrumento D.D. . ( 2014;). Rituximab-mediated Raf kinase inhibitor protein induction modulates NF-κB in Sjögren syndrome. Immunology 143: 42–51 [CrossRef] [PubMed].
    [Google Scholar]
  29. Sobotta K. , Wilsky S. , Althof N. , Wiesener N. , Wutzler P. , Henke A. . ( 2012;). Inhibition of nuclear factor κ B activation reduces Coxsackievirus B3 replication in lymphoid cells. Virus Res 163: 495–502 [CrossRef] [PubMed].
    [Google Scholar]
  30. Stracker T.H. , Cassell G.D. , Ward P. , Loo Y.M. , van Breukelen B. , Carrington-Lawrence S.D. , Hamatake R.K. , van der Vliet P.C. , Weller S.K. , other authors . ( 2004;). The Rep protein of adeno-associated virus type 2 interacts with single-stranded DNA-binding proteins that enhance viral replication. J Virol 78: 441–453 [CrossRef] [PubMed].
    [Google Scholar]
  31. Susta L. , Cornax I. , Diel D.G. , Garcia S.C. , Miller P.J. , Liu X. , Hu S. , Brown C.C. , Afonso C.L. . ( 2013;). Expression of interferon gamma by a highly virulent strain of Newcastle disease virus decreases its pathogenicity in chickens. Microb Pathog 61-62: 73–83 [CrossRef] [PubMed].
    [Google Scholar]
  32. Swayne D. E. , Glisson J. R. , McDougald L. R. , Nolan L. K. , Suarez D. L. , Nair V. L. . (editors), ( 2013;). Diseases of Poultry Ames, IA: Wiley;.
    [Google Scholar]
  33. Tang H. , Park S. , Sun S.C. , Trumbly R. , Ren G. , Tsung E. , Yeung K.C. . ( 2010;). RKIP inhibits NF-κB in cancer cells by regulating upstream signaling components of the IκB kinase complex. FEBS Lett 584: 662–668 [CrossRef] [PubMed].
    [Google Scholar]
  34. Trobaugh D.W. , Gardner C.L. , Sun C. , Haddow A.D. , Wang E. , Chapnik E. , Mildner A. , Weaver S.C. , Ryman K.D. , Klimstra W.B. . ( 2014;). RNA viruses can hijack vertebrate microRNAs to suppress innate immunity. Nature 506: 245–248 [CrossRef] [PubMed].
    [Google Scholar]
  35. Wang X. , Hussain S. , Wang E.J. , Wang X. , Li M.O. , García-Sastre A. , Beg A.A. . ( 2007;). Lack of essential role of NF-κ B p50, RelA, and cRel subunits in virus-induced type 1 IFN expression. J Immunol 178: 6770–6776 [CrossRef] [PubMed].
    [Google Scholar]
  36. Wang J. , Basagoudanavar S.H. , Wang X. , Hopewell E. , Albrecht R. , García-Sastre A. , Balachandran S. , Beg A.A. . ( 2010;). NF-κ B RelA subunit is crucial for early IFN-beta expression and resistance to RNA virus replication. J Immunol 185: 1720–1729 [CrossRef] [PubMed].
    [Google Scholar]
  37. Yeung K. , Seitz T. , Li S. , Janosch P. , McFerran B. , Kaiser C. , Fee F. , Katsanakis K.D. , Rose D.W. , other authors . ( 1999;). Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP. Nature 401: 173–177 [CrossRef] [PubMed].
    [Google Scholar]
  38. Yin R. , Ding Z. , Liu X. , Mu L. , Cong Y. , Stoeger T. . ( 2010;). Inhibition of Newcastle disease virus replication by RNA interference targeting the matrix protein gene in chicken embryo fibroblasts. J Virol Methods 167: 107–111 [CrossRef] [PubMed].
    [Google Scholar]
  39. Yin R. , Liu X. , Liu C. , Ding Z. , Zhang X. , Tian F. , Liu W. , Yu J. , Li L. , other authors . ( 2011;). Systematic selection of housekeeping genes for gene expression normalization in chicken embryo fibroblasts infected with Newcastle disease virus. Biochem Biophys Res Commun 413: 537–540 [CrossRef] [PubMed].
    [Google Scholar]
  40. Zhang S. , Sun Y. , Chen H. , Dai Y. , Zhan Y. , Yu S. , Qiu X. , Tan L. , Song C. , Ding C. . ( 2014;). Activation of the PKR/eIF2α signaling cascade inhibits replication of Newcastle disease virus. Virol J 11: 62 [CrossRef] [PubMed].
    [Google Scholar]
  41. Zhu X. , Zhou F. , Qin D. , Zeng Y. , Lv Z. , Yao S. , Lu C. . ( 2011;). Human immunodeficiency virus type 1 induces lytic cycle replication of Kaposi's-sarcoma-associated herpesvirus: role of Ras/c-Raf/MEK1/2, PI3K/AKT, and NF-κB signaling pathways. J Mol Biol 410: 1035–1051 [CrossRef] [PubMed].
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000228
Loading
/content/journal/jgv/10.1099/jgv.0.000228
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error