1887

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is the latest addition to the long list of human herpesviruses. Reactivation of latent herpesvirus infections is still a mystery. It was demonstrated recently that the phorbol ester TPA was efficient in inducing a reactivation of KSHV infection in the S phase of the cell cycle. In the present study, flow cytometry-sorted, TPA-induced, KSHV-infected haematopoietic cells (BCBL-1) were used to analyse the expression profiles of cancer-related cellular genes in the S phase of the cell cycle compared with the G0/1 phase by using microarrays. Overall, the S phase of the cell cycle seems to provide KSHV with an apt environment for a productive lytic cycle of infection. The apt conditions include cellular signalling that promotes survivability, DNA replication and lipid metabolism, while blocking cell-cycle progression to M phase. Some of the important genes that were overexpressed during the S phase of the cell cycle compared with the G0/1 phase of TPA-induced BCBL-1 cells are myeloblastosis (MYBL2), protein kinase-membrane associated tyrosine/threonine 1 (PKMYT1), ribonucleotide reductase M1 polypeptide (RRM1) and peroxisome proliferator-activated receptors delta (PPARD). Inhibition of PKMYT1 expression by the use of specific short interfering RNAs significantly lowered the TPA-induced KSHV lytic cycle of infection. The significance of these and other genes in the reactivation of KSHV is discussed in the following report. Taken together, a flow cytometry–microarray-based method to study the cellular conditions critical for the reactivation of KSHV infection is reported here for the first time.

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2006-03-01
2019-11-17
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References

  1. Akula, S. M., Ford, P. W., Whitman, A. G., Hamden, K. E., Shelton, J. G. & McCubrey, J. A. ( 2004; ). Raf promotes human herpesvirus-8 (HHV-8/KSHV) infection. Oncogene 23, 5227–5241.[CrossRef]
    [Google Scholar]
  2. Akula, S. M., Ford, P. W., Whitman, A. G., Hamden, K. E., Bryan, B. A., Cook, P. P. & McCubrey, J. A. ( 2005; ). B-Raf-dependent expression of vascular endothelial growth factor-A in Kaposi sarcoma-associated herpesvirus-infected human B cells. Blood 105, 4516–4522.[CrossRef]
    [Google Scholar]
  3. Au, P. Y. B., Martin, N., Chau, H., Moemeni, B., Chia, M., Liu, F.-F., Minden, M. & Yeh, W.-C. ( 2005; ). The oncogene PDGF-B provides a key switch from cell death to survival induced by TNF. Oncogene 24, 3196–3205.[CrossRef]
    [Google Scholar]
  4. Benedict, C. A., Norris, P. S. & Ware, C. F. ( 2002; ). To kill or be killed: viral evasion of apoptosis. Nat Immunol 3, 1013–1018.[CrossRef]
    [Google Scholar]
  5. Bepler, G., Zheng, Z., Gautam, A. & 10 other authors ( 2005; ). Ribonucleotide reductase M1 gene promoter activity, polymorphisms, population frequencies, and clinical relevance. Lung Cancer 47, 183–192.[CrossRef]
    [Google Scholar]
  6. Braissant, O., Foufelle, F., Scotto, C., Dauca, M. & Wahli, W. ( 1996; ). Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-α, -β, and -γ in the adult rat. Endocrinology 137, 354–366.
    [Google Scholar]
  7. Brown, S. M., MacLean, A. R., McKie, E. A. & Harland, J. ( 1997; ). The herpes simplex virus virulence factor ICP34.5 and the cellular protein MyD116 complex with proliferating cell nuclear antigen through the 63-amino-acid domain conserved in ICP34.5, MyD116, and GADD34. J Virol 71, 9442–9449.
    [Google Scholar]
  8. Chang, Y., Cesarman, E., Pessin, M. S., Lee, F., Culpepper, J., Knowles, D. M. & Moore, P. S. ( 1994; ). Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 266, 1865–1869.[CrossRef]
    [Google Scholar]
  9. Chang, P.-J., Shedd, D., Gradoville, L., Cho, M.-S., Chen, L.-W., Chang, J. & Miller, G. ( 2002; ). Open reading frame 50 protein of Kaposi's sarcoma-associated herpesvirus directly activates the viral PAN and K12 genes by binding to related response elements. J Virol 76, 3168–3178.[CrossRef]
    [Google Scholar]
  10. Chen, S. & Gardner, D. G. ( 2004; ). Suppression of WEE1 and stimulation of CDC25A correlates with endothelin-dependent proliferation of rat aortic smooth muscle cells. J Biol Chem 279, 13755–13763.[CrossRef]
    [Google Scholar]
  11. Deng, H., Chu, J. T., Rettig, M. B., Martinez-Maza, O. & Sun, R. ( 2002; ). Rta of the human herpesvirus 8/Kaposi sarcoma-associated herpesvirus up-regulates human interleukin-6 gene expression. Blood 100, 1919–1921.[CrossRef]
    [Google Scholar]
  12. Detta, A., Harland, J., Hanif, I., Brown, S. M. & Cruickshank, G. ( 2003; ). Proliferative activity and in vitro replication of HSV1716 in human metastatic brain tumours. J Gene Med 5, 681–689.[CrossRef]
    [Google Scholar]
  13. Dobrovolsky, V. N., Bucci, T., Heflich, R. H., Desjardins, J. & Richardson, F. C. ( 2003; ). Mice deficient for cytosolic thymidine kinase gene develop fatal kidney disease. Mol Genet Metab 78, 1–10.[CrossRef]
    [Google Scholar]
  14. Dunlop, T. W., Väisänen, S., Frank, C., Molnár, F., Sinkkonen, L. & Carlberg, C. ( 2005; ). The human peroxisome proliferator-activated receptor δ gene is a primary target of 1α,25-dihydroxyvitamin D3 and its nuclear receptor. J Mol Biol 349, 248–260.[CrossRef]
    [Google Scholar]
  15. Ford, P. W., Hamden, K. E., Whitman, A. G., McCubrey, J. A. & Akula, S. M. ( 2004; ). Vascular endothelial growth factor augments human herpesvirus-8 (HHV-8/KSHV) infection. Cancer Biol Ther 3, 876–881.[CrossRef]
    [Google Scholar]
  16. Ford, P. W., Hamden, K. E., Whitman, A. G., Bryan, B. A., Chintalgattu, V., McCubrey, J. A., Dyson, O. F. & Akula, S. M. ( 2005; ). Cigarette smoke concentrate inhibits Kaposi's sarcoma-associated herpesvirus infection. Virus Res 114, 172–176.[CrossRef]
    [Google Scholar]
  17. Gasco, M., Bell, A. K., Heath, V. & 10 other authors ( 2002; ). Epigenetic inactivation of 14-3-3 σ in oral carcinoma: association with p16INK4a silencing and human papillomavirus negativity. Cancer Res 62, 2072–2076.
    [Google Scholar]
  18. Glaunsinger, B. & Ganem, D. ( 2004; ). Highly selective escape from KSHV-mediated host mRNA shutoff and its implications for viral pathogenesis. J Exp Med 200, 391–398.[CrossRef]
    [Google Scholar]
  19. Griffiths, A., Chen, S.-H., Horsburgh, B. C. & Coen, D. M. ( 2003; ). Translational compensation of a frameshift mutation affecting herpes simplex virus thymidine kinase is sufficient to permit reactivation from latency. J Virol 77, 4703–4709.[CrossRef]
    [Google Scholar]
  20. Gustafson, E. A., Schinazi, R. F. & Fingeroth, J. D. ( 2000; ). Human herpesvirus 8 open reading frame 21 is a thymidine and thymidylate kinase of narrow substrate specificity that efficiently phosphorylates zidovudine but not ganciclovir. J Virol 74, 684–692.[CrossRef]
    [Google Scholar]
  21. Hamden, K. E., Ford, P. W., Whitman, A. G., Dyson, O. F., Cheng, S.-Y., McCubrey, J. A. & Akula, S. M. ( 2004; ). Raf-induced vascular endothelial growth factor augments Kaposi's sarcoma-associated herpesvirus infection. J Virol 78, 13381–13390.[CrossRef]
    [Google Scholar]
  22. Janssens, V. & Goris, J. ( 2001; ). Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling. Biochem J 353, 417–439.[CrossRef]
    [Google Scholar]
  23. Jenner, R. G., Albà, M. M., Boshoff, C. & Kellam, P. ( 2001; ). Kaposi's sarcoma-associated herpesvirus latent and lytic gene expression as revealed by DNA arrays. J Virol 75, 891–902.[CrossRef]
    [Google Scholar]
  24. Jové, M., Laguna, J. C. & Vázquez-Carrera, M. ( 2005; ). Agonist-induced activation releases peroxisome proliferator-activated receptor β/δ from its inhibition by palmitate-induced nuclear factor-κB in skeletal muscle cells. Biochim Biophys Acta 1734, 52–61.[CrossRef]
    [Google Scholar]
  25. Kadomatsu, K. & Muramatsu, T. ( 2004; ). Midkine and pleiotrophin in neural development and cancer. Cancer Lett 204, 127–143.[CrossRef]
    [Google Scholar]
  26. Karbownik, M., Brzezianska, E. & Lewinski, A. ( 2005; ). Increased expression of mRNA specific for thymidine kinase, deoxycytidine kinase or thymidine phosphorylase in human papillary thyroid carcinoma. Cancer Lett 225, 267–273.[CrossRef]
    [Google Scholar]
  27. Liu, F., Stanton, J. J., Wu, Z. & Piwnica-Worms, H. ( 1997; ). The human Myt1 kinase preferentially phosphorylates Cdc2 on threonine 14 and localizes to the endoplasmic reticulum and Golgi complex. Mol Cell Biol 17, 571–583.
    [Google Scholar]
  28. Lukac, D. M., Renne, R., Kirshner, J. R. & Ganem, D. ( 1998; ). Reactivation of Kaposi's sarcoma-associated herpesvirus infection from latency by expression of the ORF 50 transactivator, a homolog of the EBV R protein. Virology 252, 304–312.[CrossRef]
    [Google Scholar]
  29. Mazieres, J., He, B., You, L., Xu, Z. & Jablons, D. M. ( 2005; ). Wnt signaling in lung cancer. Cancer Lett 222, 1–10.[CrossRef]
    [Google Scholar]
  30. McAllister, S. C., Hansen, S. G., Messaoudi, I., Nikolich-Zugich, J. & Moses, A. V. ( 2005; ). Increased efficiency of phorbol ester-induced lytic reactivation of Kaposi's sarcoma-associated herpesvirus during S phase. J Virol 79, 2626–2630.[CrossRef]
    [Google Scholar]
  31. Mesri, E. A., Cesarman, E., Arvanitakis, L., Rafii, S., Moore, M. A. S., Posnett, D. N., Knowles, D. M. & Asch, A. S. ( 1996; ). Human herpesvirus-8/Kaposi's sarcoma-associated herpesvirus is a new transmissible virus that infects B cells. J Exp Med 183, 2385–2390.[CrossRef]
    [Google Scholar]
  32. Mutch, D. M., Berger, A., Mansourian, R., Rytz, A. & Roberts, M.-A. ( 2002; ). The limit fold change model: a practical approach for selecting differentially expressed genes from microarray data. BMC Bioinformatics 3, 17.[CrossRef]
    [Google Scholar]
  33. Neipel, F., Albrecht, J.-C. & Fleckenstein, B. ( 1997; ). Cell-homologous genes in the Kaposi's sarcoma-associated rhadinovirus human herpesvirus 8: determinants of its pathogenicity? J Virol 71, 4187–4192.
    [Google Scholar]
  34. Raschellà, G., Cesi, V., Amendola, R., Negroni, A., Tanno, B., Altavista, P., Tonini, G. P., De Bernardi, B. & Calabretta, B. ( 1999; ). Expression of B-myb in neuroblastoma tumors is a poor prognostic factor independent from MYCN amplification. Cancer Res 59, 3365–3368.
    [Google Scholar]
  35. Raulin, J. ( 2002; ). Human immunodeficiency virus and host cell lipids. Interesting pathways in research for a new HIV therapy. Prog Lipid Res 41, 27–65.[CrossRef]
    [Google Scholar]
  36. Ray, D., Terao, Y., Nimbalkar, D. & 8 other authors ( 2005; ). Transforming growth factor β facilitates β-TrCP-mediated degradation of Cdc25A in a Smad3-dependent manner. Mol Cell Biol 25, 3338–3347.[CrossRef]
    [Google Scholar]
  37. Renne, R., Zhong, W., Herndier, B., McGrath, M., Abbey, N., Kedes, D. & Ganem, D. ( 1996; ). Lytic growth of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in culture. Nat Med 2, 342–346.[CrossRef]
    [Google Scholar]
  38. Renne, R., Blackbourn, D., Whitby, D., Levy, J. & Ganem, D. ( 1998; ). Limited transmission of Kaposi's sarcoma-associated herpesvirus in cultured cells. J Virol 72, 5182–5188.
    [Google Scholar]
  39. Russo, J. J., Bohenzky, R. A., Chien, M.-C. & 8 other authors ( 1996; ). Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8). Proc Natl Acad Sci U S A 93, 14862–14867.[CrossRef]
    [Google Scholar]
  40. Sala, A., Casella, I., Bellon, T., Calabretta, B., Watson, R. J. & Peschle, C. ( 1996; ). B-myb promotes S phase and is a downstream target of the negative regulator p107 in human cells. J Biol Chem 271, 9363–9367.[CrossRef]
    [Google Scholar]
  41. Sano, T., Shimooka, H., Weixa, P., Segawa, A., Jian, Z., Motegi, A., Nakayama, H., Oyama, T. & Nakajima, T. ( 2004; ). Immunohistochemical expression of 14-3-3 sigma protein in various histological subtypes of uterine cervical cancers. Pathol Int 54, 743–750.[CrossRef]
    [Google Scholar]
  42. Shackelford, J. & Pagano, J. S. ( 2004; ). Tumor viruses and cell signaling pathways: deubiquitination versus ubiquitination. Mol Cell Biol 24, 5089–5093.[CrossRef]
    [Google Scholar]
  43. Siebert, S., Amos, N., Fielding, C. A., Wang, E. C. Y., Aksentijevich, I., Williams, B. D. & Brennan, P. ( 2005; ). Reduced tumor necrosis factor signaling in primary human fibroblasts containing a tumor necrosis factor receptor superfamily 1A mutant. Arthritis Rheum 52, 1287–1292.[CrossRef]
    [Google Scholar]
  44. Sun, R., Lin, S.-F., Gradoville, L., Yuan, Y., Zhu, F. & Miller, G. ( 1998; ). A viral gene that activates lytic cycle expression of Kaposi's sarcoma-associated herpesvirus. Proc Natl Acad Sci U S A 95, 10866–10871.[CrossRef]
    [Google Scholar]
  45. Wawra, E., Pöckl, E., Müllner, E. & Wintersberger, E. ( 1981; ). Effect of sodium butyrate on induction of cellular and viral DNA syntheses in polyoma virus-infected mouse kidney cells. J Virol 38, 973–981.
    [Google Scholar]
  46. Wells, N. J., Watanabe, N., Tokusumi, T., Jiang, W., Verdecia, M. A. & Hunter, T. ( 1999; ). The C-terminal domain of the Cdc2 inhibitory kinase Myt1 interacts with Cdc2 complexes and is required for inhibition of G2/M progression. J Cell Sci 112, 3361–3371.
    [Google Scholar]
  47. Whitman, A. G., Hamden, K. E., Ford, P. W., McCubrey, J. A. & Akula, S. M. ( 2004; ). Role for Raf in the entry of viruses associated with AIDS (review). Int J Oncol 25, 469–480.
    [Google Scholar]
  48. Zeng, H., Davis, C. D. & Finley, J. W. ( 2003; ). Effect of selenium-enriched broccoli diet on differential gene expression in min mouse liver. J Nutr Biochem 14, 227–231.[CrossRef]
    [Google Scholar]
  49. Zhang, F., Shao, X., Li, H., Robison, J. G., Murray, B. K. & O'Neill, K. L. ( 2001; ). A monoclonal antibody specific for human thymidine kinase 1. Hybridoma 20, 25–34.[CrossRef]
    [Google Scholar]
  50. Zhao, R. Y. & Elder, R. T. ( 2005; ). Viral infections and cell cycle G2/M regulation. Cell Res 15, 143–149.[CrossRef]
    [Google Scholar]
  51. Ziebold, U., Bartsch, O., Marais, R., Ferrari, S. & Klempnauer, K.-H. ( 1997; ). Phosphorylation and activation of B-Myb by cyclin A–Cdk2. Curr Biol 7, 253–260.[CrossRef]
    [Google Scholar]
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Raw microarray data for one representative trial [ Excel spreadsheet] (119 KB)



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