1887

Journal of General Virology header logo

Volume 87, Issue 3

Identifying cellular genes crucial for the reactivation of Kaposi's sarcoma-associated herpesvirus latency Free

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.

  • Received:
  • Accepted:
  • Published Online:
SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81603-0
2006-03-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/3/519.html?itemId=/content/journal/jgv/10.1099/vir.0.81603-0&mimeType=html&fmt=ahah

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 1 α ,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- κ B 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]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81603-0
Loading
Identifying cellular genes crucial for the reactivation of Kaposi's sarcoma-associated herpesvirus latency
J. Gen. Virol. 87, 519 (2006); https://doi.org/10.1099/vir.0.81603-0
/content/journal/jgv/10.1099/vir.0.81603-0
/content/journal/jgv/10.1099/vir.0.81603-0
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Most cited 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