1887

Abstract

Marek’s disease virus (MDV), one of the most potent oncogenic herpesviruses, leads to highly contagious immunosuppressive and neoplastic disease in susceptible chickens. Previous studies mainly focused on the roles of host genes modulated by MDV in the virological rather than the neoplastic stage of disease. To investigate the molecular mechanisms of tumorigenesis in Marek’s disease further, a microarray analysis with Affymetrix Gene-Chip Chicken Genome Arrays was performed in a non-lymphoid tissue liver during the neoplastic stage. Of the 32 773 chicken transcriptions arrayed on a chip, 269 genes were significantly differentially expressed during the neoplastic stage caused by MDV infection (upregulated, 175; downregulated, 94). The altered genomic expression of 15 randomly selected genes was confirmed by real-time RT-PCR. Biological functions and pathways of the group of 269 differentially expressed genes were analysed by using a bioinformatics tool (, Ingenuity Pathway Analysis). The results revealed that 19 possible gene networks with intermolecular connections and 22 significant metabolic and signalling pathways (≤0.05) among 137 differentially expressed genes. These 137 genes were classified into a number of functional groups that included genetic disorder, cancer, cellular growth and proliferation, and cell death. In summary, the investigation of global host-gene expression, providing the biological functions of differentially expressed genes in lymphoid tumours of the liver in response to MDV infections, may contribute to a basic understanding of the molecular mechanisms involved in tumorigenesis following MDV infection.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.034066-0
2011-12-01
2022-01-24
Loading full text...

Full text loading...

/deliver/fulltext/jgv/92/12/2724.html?itemId=/content/journal/jgv/10.1099/vir.0.034066-0&mimeType=html&fmt=ahah

References

  1. Abdul-Careem M. F., Hunter B. D., Nagy E., Read L. R., Sanei B., Spencer J. L., Sharif S. 2006a; Development of a real-time PCR assay using SYBR Green chemistry for monitoring Marek’s disease virus genome load in feather tips. J Virol Methods 133:34–40 [View Article][PubMed]
    [Google Scholar]
  2. Abdul-Careem M. F., Hunter B. D., Sarson A. J., Mayameei A., Zhou H., Sharif S. 2006b; Marek’s disease virus-induced transient paralysis is associated with cytokine gene expression in the nervous system. Viral Immunol 19:167–176 [View Article][PubMed]
    [Google Scholar]
  3. Abdul-Careem M. F., Hunter B. D., Lee L. F., Fairbrother J. H., Haghighi H. R., Read L., Parvizi P., Heidari M., Sharif S. 2008a; Host responses in the bursa of Fabricius of chickens infected with virulent Marek’s disease virus. Virology 379:256–265 [View Article][PubMed]
    [Google Scholar]
  4. Abdul-Careem M. F., Hunter B. D., Sarson A. J., Parvizi P., Haghighi H. R., Read L., Heidari M., Sharif S. 2008b; Host responses are induced in feathers of chickens infected with Marek’s disease virus. Virology 370:323–332 [View Article][PubMed]
    [Google Scholar]
  5. Adams S. C., Xing Z., Li J., Cardona C. J. 2009; Immune-related gene expression in response to H11N9 low pathogenic avian influenza virus infection in chicken and Pekin duck peripheral blood mononuclear cells. Mol Immunol 46:1744–1749 [View Article][PubMed]
    [Google Scholar]
  6. Aikawa T., Gunn J., Spong S. M., Klaus S. J., Korc M. 2006; Connective tissue growth factor-specific antibody attenuates tumor growth, metastasis, and angiogenesis in an orthotopic mouse model of pancreatic cancer. Mol Cancer Ther 5:1108–1116 [View Article][PubMed]
    [Google Scholar]
  7. Arcellana-Panlilio M., Robbins S. M. 2002; Cutting-edge technology. I. Global gene expression profiling using DNA microarrays. Am J Physiol Gastrointest Liver Physiol 282:G397–G402[PubMed] [CrossRef]
    [Google Scholar]
  8. Bataller R., Brenner D. A. 2001; Hepatic stellate cells as a target for the treatment of liver fibrosis. Semin Liver Dis 21:437–451 [View Article][PubMed]
    [Google Scholar]
  9. Bataller R., Brenner D. A. 2005; Liver fibrosis. J Clin Invest 115:209–218[PubMed] [CrossRef]
    [Google Scholar]
  10. Branton M. H., Kopp J. B. 1999; TGF-β and fibrosis. Microbes Infect 1:1349–1365 [View Article][PubMed]
    [Google Scholar]
  11. Brown A. C., Smith L. P., Kgosana L., Baigent S. J., Nair V., Allday M. J. 2009; Homodimerization of the Meq viral oncoprotein is necessary for induction of T-cell lymphoma by Marek’s disease virus. J Virol 83:11142–11151 [View Article][PubMed]
    [Google Scholar]
  12. Calnek B. W. 2001; Pathogenesis of Marek’s disease virus infection. Curr Top Microbiol Immunol 255:25–55[PubMed]
    [Google Scholar]
  13. Carmena M., Earnshaw W. C. 2003; The cellular geography of aurora kinases. Nat Rev Mol Cell Biol 4:842–854 [View Article][PubMed]
    [Google Scholar]
  14. 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 [View Article][PubMed]
    [Google Scholar]
  15. Chen X., Liang S., Zheng W., Liao Z., Shang T., Ma W. 2008; Meta-analysis of nasopharyngeal carcinoma microarray data explores mechanism of EBV-regulated neoplastic transformation. BMC Genomics 9:322–332 [View Article][PubMed]
    [Google Scholar]
  16. Cretu A., Sha X., Tront J., Hoffman B., Liebermann D. A. 2009; Stress sensor Gadd45 genes as therapeutic targets in cancer. Cancer Ther 7:A268–276[PubMed]
    [Google Scholar]
  17. DeBerardinis R. J., Sayed N., Ditsworth D., Thompson C. B. 2008a; Brick by brick: metabolism and tumor cell growth. Curr Opin Genet Dev 18:54–61 [View Article][PubMed]
    [Google Scholar]
  18. DeBerardinis R. J., Lum J. J., Hatzivassiliou G., Thompson C. B. 2008b; The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7:11–20 [View Article][PubMed]
    [Google Scholar]
  19. Fingleton B. 2006; Matrix metalloproteinases: roles in cancer and metastasis. Front Biosci 11:479–491 [View Article][PubMed]
    [Google Scholar]
  20. Haq K., Brisbin J. T., Thanthrige-Don N., Heidari M., Sharif S. 2010; Transcriptome and proteome profiling of host responses to Marek’s disease virus in chickens. Vet Immunol Immunopathol 138:292–302 [View Article][PubMed]
    [Google Scholar]
  21. Hayward D. G., Clarke R. B., Faragher A. J., Pillai M. R., Hagan I. M., Fry A. M. 2004; The centrosomal kinase Nek2 displays elevated levels of protein expression in human breast cancer. Cancer Res 64:7370–7376 [View Article][PubMed]
    [Google Scholar]
  22. Heidari M., Sarson A. J., Huebner M., Sharif S., Kireev D., Zhou H. 2010; Marek’s disease virus-induced immunosuppression: array analysis of chicken immune response gene expression profiling. Viral Immunol 23:309–319 [View Article][PubMed]
    [Google Scholar]
  23. Ivaska J., Pallari H. M., Nevo J., Eriksson J. E. 2007; Novel functions of vimentin in cell adhesion, migration, and signaling. Exp Cell Res 313:2050–2062 [View Article][PubMed]
    [Google Scholar]
  24. Jones D., Lee L., Liu J. L., Kung H. J., Tillotson J. K. 1992; Marek disease virus encodes a basic-leucine zipper gene resembling the fos/jun oncogenes that is highly expressed in lymphoblastoid tumors. Proc Natl Acad Sci U S A 89:4042–4046 [View Article][PubMed]
    [Google Scholar]
  25. Karaca G., Anobile J., Downs D., Burnside J., Schmidt C. J. 2004; Herpesvirus of turkeys: microarray analysis of host gene responses to infection. Virology 318:102–111 [View Article][PubMed]
    [Google Scholar]
  26. Karlsson S., Holmberg E., Askerlund A., Levan K. K. 2007; Altered transforming growth factor-β pathway expression pattern in rat endometrial cancer. Cancer Genet Cytogenet 177:43–50 [View Article][PubMed]
    [Google Scholar]
  27. Lapenna S., Giordano A. 2009; Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov 8:547–566 [View Article][PubMed]
    [Google Scholar]
  28. Lee J. Y., Song J. J., Wooming A., Li X., Zhou H., Bottje W. G., Kong B. W. 2010; Transcriptional profiling of host gene expression in chicken embryo lung cells infected with laryngotracheitis virus. BMC Genomics 11:445–459 [View Article][PubMed]
    [Google Scholar]
  29. Li J., Liu C., Zhang Y., Shi W., Qu P., Liu A., Yan F. 2008; Replication kinetics of Marek's disease virus in chicken peripheral blood lymphocyte and feather tips. Chin J Prev Vet Med 30:879–884
    [Google Scholar]
  30. Lu Z., Qin A., Qian K., Chen X., Jin W., Zhu Y., Eltahir Y. M. 2010; Proteomic analysis of the host response in the bursa of Fabricius of chickens infected with Marek’s disease virus. Virus Res 153:250–257 [View Article][PubMed]
    [Google Scholar]
  31. Malumbres M., Barbacid M. 2009; Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 9:153–166 [View Article][PubMed]
    [Google Scholar]
  32. Mondal G., Sengupta S., Panda C. K., Gollin S. M., Saunders W. S., Roychoudhury S. 2007; Overexpression of Cdc20 leads to impairment of the spindle assembly checkpoint and aneuploidization in oral cancer. Carcinogenesis 28:81–92 [View Article][PubMed]
    [Google Scholar]
  33. Morgan R. W., Sofer L., Anderson A. S., Bernberg E. L., Cui J., Burnside J. 2001; Induction of host gene expression following infection of chicken embryo fibroblasts with oncogenic Marek’s disease virus. J Virol 75:533–539 [View Article][PubMed]
    [Google Scholar]
  34. Osterrieder N., Kamil J. P., Schumacher D., Tischer B. K., Trapp S. 2006; Marek’s disease virus: from miasma to model. Nat Rev Microbiol 4:283–294 [View Article][PubMed]
    [Google Scholar]
  35. Quéré P., Rivas C., Ester K., Novak R., Ragland W. L. 2005; Abundance of IFN-α and IFN-γ mRNA in blood of resistant and susceptible chickens infected with Marek’s disease virus (MDV) or vaccinated with turkey herpesvirus; and MDV inhibition of subsequent induction of IFN gene transcription. Arch Virol 150:507–519 [View Article][PubMed]
    [Google Scholar]
  36. Rajagopalan H., Lengauer C. 2004; Aneuploidy and cancer. Nature 432:338–341 [View Article][PubMed]
    [Google Scholar]
  37. Rath N. C., Parcells M. S., Xie H., Santin E. 2003; Characterization of a spontaneously transformed chicken mononuclear cell line. Vet Immunol Immunopathol 96:93–104 [View Article][PubMed]
    [Google Scholar]
  38. Ross N. L. 1999; T-cell transformation by Marek’s disease virus. Trends Microbiol 7:22–29 [View Article][PubMed]
    [Google Scholar]
  39. Sarson A. J., Parvizi P., Lepp D., Quinton M., Sharif S. 2008; Transcriptional analysis of host responses to Marek’s disease virus infection in genetically resistant and susceptible chickens. Anim Genet 39:232–240 [View Article][PubMed]
    [Google Scholar]
  40. Tfelt-Hansen J., Kanuparthi D., Chattopadhyay N. 2006; The emerging role of pituitary tumor transforming gene in tumorigenesis. Clin Med Res 4:130–137 [View Article][PubMed]
    [Google Scholar]
  41. Thanthrige-Don N., Parvizi P., Sarson A. J., Shack L. A., Burgess S. C., Sharif S. 2010; Proteomic analysis of host responses to Marek’s disease virus infection in spleens of genetically resistant and susceptible chickens. Dev Comp Immunol 34:699–704 [View Article][PubMed]
    [Google Scholar]
  42. Vairapandi M., Balliet A. G., Hoffman B., Liebermann D. A. 2002; GADD45b and GADD45g are cdc2/cyclinB1 kinase inhibitors with a role in S and G2/M cell cycle checkpoints induced by genotoxic stress. J Cell Physiol 192:327–338 [View Article][PubMed]
    [Google Scholar]
  43. Venugopal K. 2000; Marek’s disease: an update on oncogenic mechanisms and control. Res Vet Sci 69:17–23 [View Article][PubMed]
    [Google Scholar]
  44. Witter R. L., Sharma J. M., Offenbecker L. 1976; Turkey herpesvirus infection in chickens: induction of lymphoproliferative lesions and characterization of vaccinal immunity against Marek’s disease. Avian Dis 20:676–692 [View Article][PubMed]
    [Google Scholar]
  45. Wong R. T., Hon C. C., Zeng F., Leung F. C. 2007; Screening of differentially expressed transcripts in infectious bursal disease virus-induced apoptotic chicken embryonic fibroblasts by using cDNA microarrays. J Gen Virol 88:1785–1796 [View Article][PubMed]
    [Google Scholar]
  46. Xu S., Xue C., Li J., Bi Y., Cao Y. 2011; Marek’s disease virus type 1 microRNA miR-M3 suppresses cisplatin-induced apoptosis by targeting Smad2 of the transforming growth factor beta signal pathway. J Virol 85:276–285 [View Article][PubMed]
    [Google Scholar]
  47. Zhang L., Hong K., Zhang J., Pagano J. S. 2004; Multiple signal transducers and activators of transcription are induced by EBV LMP-1. Virology 323:141–152 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.034066-0
Loading
/content/journal/jgv/10.1099/vir.0.034066-0
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Most cited this month Most Cited RSS feed

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