1887

Abstract

Infectious bursal disease virus (IBDV) induces apoptosis and immunosuppression. To understand the molecular mechanisms involved in the pathogenesis of infectious bursal disease (IBD) and the host-directed antiviral responses, cDNA microarrays were used to identify the differentially expressed transcripts in IBDV-infected chicken embryonic fibroblasts. The results suggest a general suppression of surface receptors, including CD40 ligand and SEMA4D. These are related to T- and B-cell activation and differentiation, which may contribute to the immunosuppression of IBD. In addition, activation of genes involved in Toll-like receptor- and interferon (IFN)-mediated antiviral responses was detected. In particular, upregulation of Toll-like receptor 3, a double-stranded (ds) RNA receptor, and MX1, an IFN-inducible antiviral GTPase, may represent the possible host-directed defence responses against the virus and its dsRNA genome. Interestingly, several lines of evidence suggest the modulation of G protein-coupled receptors and receptor tyrosine kinase signalling pathways, especially the possible transactivation of epidermal growth factor receptor by lysophosphatidic acid. Alteration of these may contribute to the previously reported activation of mitogen-activated protein kinases upon IBDV infection, resulting in macrophage activation and inflammatory responses. Additionally, numerous target genes and inducers of nuclear factor kappa B (NF-B) were upregulated profoundly, implying that IBDV may modulate host-cell survival and apoptosis to support its replication and facilitate viral spread through NF-B activation. In summary, this investigation of host-gene expression unravelled the candidate physiological pathways involved in host–virus interaction on a molecular level, providing a foundation for researchers to design experiments based on testable hypotheses targeting individual genes.

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2007-06-01
2024-03-28
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References

  1. Baetu T. M., Hiscott J. 2002; On the TRAIL to apoptosis. Cytokine Growth Factor Rev 13:199–207 [CrossRef]
    [Google Scholar]
  2. Burkhardt E., Muller H. 1987; Susceptibility of chicken blood lymphoblasts and monocytes to infectious bursal disease virus (IBDV). Arch Virol 94:297–303 [CrossRef]
    [Google Scholar]
  3. Burnside J., Neiman P., Tang J., Basom R., Talbot R., Aronszajn M., Burt D., Delrow J. 2005; Development of a cDNA array for chicken gene expression analysis. BMC Genomics 6:13 [CrossRef]
    [Google Scholar]
  4. Chelbi-Alix M. K., Vidy A., El Bougrini J., Blondel D. 2006; Rabies viral mechanisms to escape the IFN system: the viral protein P interferes with IRF-3, Stat1, and PML nuclear bodies. J Interferon Cytokine Res 26:271–280 [CrossRef]
    [Google Scholar]
  5. Chokki M., Mitsuhashi H., Kamimura T. 2006; Metalloprotease-dependent amphiregulin release mediates tumor necrosis factor-alpha-induced IL-8 secretion in the human airway epithelial cell line NCI-H292. Life Sci 78:3051–3057 [CrossRef]
    [Google Scholar]
  6. Churchill G. A. 2002; Fundamentals of experimental design for cDNA microarrays. Nat Genet 32, (Suppl.):490–495 [CrossRef]
    [Google Scholar]
  7. Clarke P., Tyler K. L. 2003; Reovirus-induced apoptosis: a minireview. Apoptosis 8:141–150 [CrossRef]
    [Google Scholar]
  8. Cui X., Hawari F., Alsaaty S., Lawrence M., Combs C. A., Geng W., Rouhani F. N., Miskinis D., Levine S. J. 2002; Identification of ARTS-1 as a novel TNFR1-binding protein that promotes TNFR1 ectodomain shedding. J Clin Invest 110:515–526 [CrossRef]
    [Google Scholar]
  9. Dobos P., Hill B. J., Hallett R., Kells D. T., Becht H., Teninges D. 1979; Biophysical and biochemical characterization of five animal viruses with bisegmented double-stranded RNA genomes. J Virol 32:593–605
    [Google Scholar]
  10. Espert L., Rey C., Gonzalez L., Degols G., Chelbi-Alix M. K., Mechti N., Gongora C. 2004; The exonuclease ISG20 is directly induced by synthetic dsRNA via NF-kappaB and IRF1 activation. Oncogene 23:4636–4640 [CrossRef]
    [Google Scholar]
  11. Ferguson S. S. 2001; Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling. Pharmacol Rev 53:1–24
    [Google Scholar]
  12. Fernandez-Arias A., Martinez S., Rodriguez J. F. 1997; The major antigenic protein of infectious bursal disease virus, VP2, is an apoptotic inducer. J Virol 71:8014–8018
    [Google Scholar]
  13. Groskreutz D. J., Monick M. M., Powers L. S., Yarovinsky T. O., Look D. C., Hunninghake G. W. 2006; Respiratory syncytial virus induces TLR3 protein and protein kinase R, leading to increased double-stranded RNA responsiveness in airway epithelial cells. J Immunol 176:1733–1740 [CrossRef]
    [Google Scholar]
  14. Harte M. T., Haga I. R., Maloney G., Gray P., Reading P. C., Bartlett N. W., Smith G. L., Bowie A., O'Neill L. A. 2003; The poxvirus protein A52R targets Toll-like receptor signaling complexes to suppress host defense. J Exp Med 197:343–351 [CrossRef]
    [Google Scholar]
  15. Heinz S., Haehnel V., Karaghiosoff M., Schwarzfischer L., Muller M., Krause S. W., Rehli M. 2003; Species-specific regulation of Toll-like receptor 3 genes in men and mice. J Biol Chem 278:21502–21509 [CrossRef]
    [Google Scholar]
  16. Higashiyama S., Nanba D. 2005; ADAM-mediated ectodomain shedding of HB-EGF in receptor cross-talk. Biochim Biophys Acta 1751:110–117 [CrossRef]
    [Google Scholar]
  17. Hiscott J., Kwon H., Genin P. 2001; Hostile takeovers: viral appropriation of the NF-kappaB pathway. J Clin Invest 107:143–151 [CrossRef]
    [Google Scholar]
  18. Hong J. R., Gong H. Y., Wu J. L. 2002; IPNV VP5, a novel anti-apoptosis gene of the Bcl-2 family, regulates Mcl-1 and viral protein expression. Virology 295:217–229 [CrossRef]
    [Google Scholar]
  19. Inoue C. N. 2002; LPA as a determinant of mesangial growth and apoptosis. Semin Nephrol 22:415–422 [CrossRef]
    [Google Scholar]
  20. Izmailova E., Bertley F. M., Huang Q., Makori N., Miller C. J., Young R. A., Aldovini A. 2003; HIV-1 Tat reprograms immature dendritic cells to express chemoattractants for activated T cells and macrophages. Nat Med 9:191–197 [CrossRef]
    [Google Scholar]
  21. Jungmann A., Nieper H., Muller H. 2001; Apoptosis is induced by infectious bursal disease virus replication in productively infected cells as well as in antigen-negative cells in their vicinity. J Gen Virol 82:1107–1115
    [Google Scholar]
  22. Kanazawa N., Kurosaki M., Sakamoto N., Enomoto N., Itsui Y., Yamashiro T., Tanabe Y., Maekawa S., Nakagawa M. other authors 2004; Regulation of hepatitis C virus replication by interferon regulatory factor 1. J Virol 78:9713–9720 [CrossRef]
    [Google Scholar]
  23. Khatri M., Sharma J. M. 2006; Infectious bursal disease virus infection induces macrophage activation via p38 MAPK and NF-kappaB pathways. Virus Res 118:70–77 [CrossRef]
    [Google Scholar]
  24. Khatri M., Palmquist J. M., Cha R. M., Sharma J. M. 2005; Infection and activation of bursal macrophages by virulent infectious bursal disease virus. Virus Res 113:44–50 [CrossRef]
    [Google Scholar]
  25. Kim I. J., Karaca K., Pertile T. L., Erickson S. A., Sharma J. M. 1998; Enhanced expression of cytokine genes in spleen macrophages during acute infection with infectious bursal disease virus in chickens. Vet Immunol Immunopathol 61:331–341 [CrossRef]
    [Google Scholar]
  26. Kishi Y., Okudaira S., Tanaka M., Hama K., Shida D., Kitayama J., Yamori T., Aoki J., Fujimaki T., Arai H. 2006; Autotaxin is overexpressed in glioblastoma multiforme and contributes to cell motility of glioblastoma by converting lysophosphatidylcholine to lysophosphatidic acid. J Biol Chem 281:17492–17500 [CrossRef]
    [Google Scholar]
  27. Klein E., Teramoto N., Gogolak P., Nagy N., Bjorkholm M. 1999; LMP-1, the Epstein-Barr virus-encoded oncogene with a B cell activating mechanism similar to CD40. Immunol Lett 68:147–154 [CrossRef]
    [Google Scholar]
  28. Kornbluth R. S. 2000; The emerging role of CD40 ligand in HIV infection. J Leukoc Biol 68:373–382
    [Google Scholar]
  29. Kosugi A., Saitoh S., Narumiya S., Miyake K., Hamaoka T. 1994; Activation-induced expression of thymic shared antigen-1 on T lymphocytes and its inhibitory role for TCR-mediated IL-2 production. Int Immunol 6:1967–1976 [CrossRef]
    [Google Scholar]
  30. Larsen R., Rokenes T. P., Robertsen B. 2004; Inhibition of infectious pancreatic necrosis virus replication by Atlantic salmon Mx1 protein. J Virol 78:7938–7944 [CrossRef]
    [Google Scholar]
  31. Li K., Foy E., Ferreon J. C., Nakamura M., Ferreon A. C., Ikeda M., Ray S. C., Gale M. Jr, Lemon S. M. 2005; Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF. Proc Natl Acad Sci U S A 102:2992–2997 [CrossRef]
    [Google Scholar]
  32. Liebmann C. 2001; Regulation of MAP kinase activity by peptide receptor signalling pathway: paradigms of multiplicity. Cell Signal 13:777–785 [CrossRef]
    [Google Scholar]
  33. Liu M., Vakharia V. N. 2006; Nonstructural protein of infectious bursal disease virus inhibits apoptosis at the early stage of virus infection. J Virol 80:3369–3377 [CrossRef]
    [Google Scholar]
  34. Liu H. C., Niikura M., Fulton J. E., Cheng H. H. 2003; Identification of chicken lymphocyte antigen 6 complex, locus E (LY6E, alias SCA2) as a putative Marek's disease resistance gene via a virus-host protein interaction screen. Cytogenet Genome Res 102:304–308 [CrossRef]
    [Google Scholar]
  35. Lombardo E., Maraver A., Espinosa I., Fernandez-Arias A., Rodriguez J. F. 2000; VP5, the nonstructural polypeptide of infectious bursal disease virus, accumulates within the host plasma membrane and induces cell lysis. Virology 277:345–357 [CrossRef]
    [Google Scholar]
  36. MacMicking J. D. 2004; IFN-inducible GTPases and immunity to intracellular pathogens. Trends Immunol 25:601–609 [CrossRef]
    [Google Scholar]
  37. McCarthy J. V., Ni J., Dixit V. M. 1998; RIP2 is a novel NF-kappaB-activating and cell death-inducing kinase. J Biol Chem 273:16968–16975 [CrossRef]
    [Google Scholar]
  38. Minogue S., Waugh M. G., De Matteis M. A., Stephens D. J., Berditchevski F., Hsuan J. J. 2006; Phosphatidylinositol 4-kinase is required for endosomal trafficking and degradation of the EGF receptor. J Cell Sci 119:571–581 [CrossRef]
    [Google Scholar]
  39. Mizuno E., Iura T., Mukai A., Yoshimori T., Kitamura N., Komada M. 2005; Regulation of epidermal growth factor receptor down-regulation by UBPY-mediated deubiquitination at endosomes. Mol Biol Cell 16:5163–5174 [CrossRef]
    [Google Scholar]
  40. Moughal N. A., Waters C., Sambi B., Pyne S., Pyne N. J. 2004; Nerve growth factor signaling involves interaction between the Trk A receptor and lysophosphatidate receptor 1 systems: nuclear translocation of the lysophosphatidate receptor 1 and Trk A receptors in pheochromocytoma 12 cells. Cell Signal 16:127–136 [CrossRef]
    [Google Scholar]
  41. Muller H., Lange H., Becht H. 1986; Formation, characterization and interfering capacity of a small plaque mutant and of incomplete virus particles of infectious bursal disease virus. Virus Res 4:297–309 [CrossRef]
    [Google Scholar]
  42. Murph M. M., Scaccia L. A., Volpicelli L. A., Radhakrishna H. 2003; Agonist-induced endocytosis of lysophosphatidic acid-coupled LPA1/EDG-2 receptors via a dynamin2- and Rab5-dependent pathway. J Cell Sci 116:1969–1980 [CrossRef]
    [Google Scholar]
  43. Nitschke L., Tsubata T. 2004; Molecular interactions regulate BCR signal inhibition by CD22 and CD72. Trends Immunol 25:543–550 [CrossRef]
    [Google Scholar]
  44. O'Donnell S. M., Holm G. H., Pierce J. M., Tian B., Watson M. J., Chari R. S., Ballard D. W., Brasier A. R., Dermody T. S. 2006; Identification of an NF-kappaB-dependent gene network in cells infected by mammalian reovirus. J Virol 80:1077–1086 [CrossRef]
    [Google Scholar]
  45. Okada T., Maeda A., Iwamatsu A., Gotoh K., Kurosaki T. 2000; BCAP: the tyrosine kinase substrate that connects B cell receptor to phosphoinositide 3-kinase activation. Immunity 13:817–827 [CrossRef]
    [Google Scholar]
  46. Park S. Y., Seol J. W., Lee Y. J., Cho J. H., Kang H. S., Kim I. S., Park S. H., Kim T. H., Yim J. H. other authors 2004; IFN-gamma enhances TRAIL-induced apoptosis through IRF-1. Eur J Biochem 271:4222–4228 [CrossRef]
    [Google Scholar]
  47. Patel S., Zuckerman M., Smith M. 2003; Real-time quantitative PCR of Epstein-Barr virus BZLF1 DNA using the LightCycler. J Virol Methods 109:227–233 [CrossRef]
    [Google Scholar]
  48. Rami A., Rabie A. 1990; Delayed synaptogenesis in the dentate gyrus of the thyroid-deficient developing rat. Dev Neurosci 12:398–405 [CrossRef]
    [Google Scholar]
  49. Rasschaert J., Ladriere L., Urbain M., Dogusan Z., Katabua B., Sato S., Akira S., Gysemans C., Mathieu C., Eizirik D. L. 2005; Toll-like receptor 3 and STAT-1 contribute to double-stranded RNA+ interferon-gamma-induced apoptosis in primary pancreatic beta-cells. J Biol Chem 280:33984–33991 [CrossRef]
    [Google Scholar]
  50. Rosenberger J. K., Fries P. A., Cloud S. S., Wilson R. A. 1985; In vitro and in vivo characterization of avian Escherichia coli. II. Factors associated with pathogenicity. Avian Dis 29:1094–1107 [CrossRef]
    [Google Scholar]
  51. Roth W., Kermer P., Krajewska M., Welsh K., Davis S., Krajewski S., Reed J. C. 2003; Bifunctional apoptosis inhibitor (BAR) protects neurons from diverse cell death pathways. Cell Death Differ 10:1178–1187 [CrossRef]
    [Google Scholar]
  52. Saitoh S., Kosugi A., Noda S., Yamamoto N., Ogata M., Minami Y., Miyake K., Hamaoka T. 1995; Modulation of TCR-mediated signaling pathway by thymic shared antigen-1 (TSA-1)/stem cell antigen-2 (Sca-2). J Immunol 155:5574–5581
    [Google Scholar]
  53. Schroder M., Bowie A. G. 2005; TLR3 in antiviral immunity: key player or bystander?. Trends Immunol 26:462–468 [CrossRef]
    [Google Scholar]
  54. Schweickart V. L., Epp A., Raport C. J., Gray P. W. 2000; CCR11 is a functional receptor for the monocyte chemoattractant protein family of chemokines. J Biol Chem 275:9550–9556 [CrossRef]
    [Google Scholar]
  55. Shi G. X., Harrison K., Han S. B., Moratz C., Kehrl J. H. 2004; Toll-like receptor signaling alters the expression of regulator of G protein signaling proteins in dendritic cells: implications for G protein-coupled receptor signaling. J Immunol 172:5175–5184 [CrossRef]
    [Google Scholar]
  56. Smit M. J., Vink C., Verzijl D., Casarosa P., Bruggeman C. A., Leurs R. 2003; Virally encoded G protein-coupled receptors: targets for potentially innovative anti-viral drug development. Curr Drug Targets 4:431–441 [CrossRef]
    [Google Scholar]
  57. Stang E., Blystad F. D., Kazazic M., Bertelsen V., Brodahl T., Raiborg C., Stenmark H., Madshus I. H. 2004; Cbl-dependent ubiquitination is required for progression of EGF receptors into clathrin-coated pits. Mol Biol Cell 15:3591–3604 [CrossRef]
    [Google Scholar]
  58. Tai D. I., Tsai S. L., Chen T. C., Lo S. K., Chang Y. H., Liaw Y. F. 2001; Modulation of tumor necrosis factor receptors 1 and 2 in chronic hepatitis B and C: the differences and implications in pathogenesis. J Biomed Sci 8:321–327 [CrossRef]
    [Google Scholar]
  59. Takegahara N., Kumanogoh A., Kikutani H. 2005; Semaphorins: a new class of immunoregulatory molecules. Philos Trans R Soc Lond B Biol Sci 360:1673–1680 [CrossRef]
    [Google Scholar]
  60. Tanaka H., Fujita N., Tsuruo T. 2005; 3-Phosphoinositide-dependent protein kinase-1-mediated IkappaB kinase beta (IkkB) phosphorylation activates NF-kappaB signaling. J Biol Chem 280:40965–40973 [CrossRef]
    [Google Scholar]
  61. Tanimura N., Sharma J. M. 1998; In-situ apoptosis in chickens infected with infectious bursal disease virus. J Comp Pathol 118:15–27 [CrossRef]
    [Google Scholar]
  62. Tham K. M., Moon C. D. 1996; Apoptosis in cell cultures induced by infectious bursal disease virus following in vitro infection. Avian Dis 40:109–113 [CrossRef]
    [Google Scholar]
  63. Tsuda M., Matsumoto K., Inoue H., Matsumura M., Nakano T., Mori A., Azuma M., Nakanishi Y. 2005; Expression of B7-H1 and B7-DC on the airway epithelium is enhanced by double-stranded RNA. Biochem Biophys Res Commun 330:263–270 [CrossRef]
    [Google Scholar]
  64. van Kooten C., Banchereau J. 2000; CD40–CD40 ligand. J Leukoc Biol 67:2–17
    [Google Scholar]
  65. Vasconcelos A. C., Lam K. M. 1994; Apoptosis induced by infectious bursal disease virus. J Gen Virol 75:1803–1806 [CrossRef]
    [Google Scholar]
  66. Vasconcelos A. C., Lam K. M. 1995; Apoptosis in chicken embryos induced by the infectious bursal disease virus. J Comp Pathol 112:327–338 [CrossRef]
    [Google Scholar]
  67. Vidalain P. O., Azocar O., Lamouille B., Astier A., Rabourdin-Combe C., Servet-Delprat C. 2000; Measles virus induces functional TRAIL production by human dendritic cells. J Virol 74:556–559 [CrossRef]
    [Google Scholar]
  68. Vieira A. V., Lamaze C., Schmid S. L. 1996; Control of EGF receptor signaling by clathrin-mediated endocytosis. Science 274:2086–2089 [CrossRef]
    [Google Scholar]
  69. Wu J., Cunnick J. M. 2002; Trans-regulation of epidermal growth factor receptor by lysophosphatidic acid and G protein-coupled receptors. Biochim Biophys Acta 1582:100–106 [CrossRef]
    [Google Scholar]
  70. Xie Y., Meier K. E. 2004; Lysophospholipase D and its role in LPA production. Cell Signal 16:975–981 [CrossRef]
    [Google Scholar]
  71. Xue C. Y., Lim B. L. 2001; In situ localization of infectious bursal disease virus-binding cells by a biotin-streptavidin system. Avian Dis 45:504–511 [CrossRef]
    [Google Scholar]
  72. Yao K., Vakharia V. N. 2001; Induction of apoptosis in vitro by the 17-kDa nonstructural protein of infectious bursal disease virus: possible role in viral pathogenesis. Virology 285:50–58 [CrossRef]
    [Google Scholar]
  73. Yao K., Goodwin M. A., Vakharia V. N. 1998; Generation of a mutant infectious bursal disease virus that does not cause bursal lesions. J Virol 72:2647–2654
    [Google Scholar]
  74. Yeh H. Y., Rautenschlein S., Sharma J. M. 2002; Protective immunity against infectious bursal disease virus in chickens in the absence of virus-specific antibodies. Vet Immunol Immunopathol 89:149–158 [CrossRef]
    [Google Scholar]
  75. Zhang M., Li X., Pang X., Ding L., Wood O., Clouse K., Hewlett I., Dayton A. I. 2001; Identification of a potential HIV-induced source of bystander-mediated apoptosis in T cells: upregulation of trail in primary human macrophages by HIV-1 tat. J Biomed Sci 8:290–296 [CrossRef]
    [Google Scholar]
  76. Zhou J., Law H. K., Cheung C. Y., Ng I. H., Peiris J. S., Lau Y. L. 2006; Functional tumor necrosis factor-related apoptosis-inducing ligand production by avian influenza virus-infected macrophages. J Infect Dis 193:945–953 [CrossRef]
    [Google Scholar]
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