1887

Abstract

Epstein–Barr virus (EBV) expresses two transcription factors, Rta and Zta, during the immediate–early stage of the lytic cycle to activate the transcription of early and late genes. This study finds that 0.31 mM protoapigenone from (Gaud.) inhibits the expression of EBV lytic proteins, including Rta, Zta, EA-D and VCA, in P3HR1 cells after lytic induction with 12--tetradecanoylphorbol-13-acetate and sodium butyrate. The lack of expression of EBV lytic proteins after protoapigenone treatment is attributed to the inhibition of the transactivation function of Zta because protoapigenone reduces the transactivation activity of Zta and Gal4–Zta, which contains the transactivation domain of Zta fused with Gal4. In contrast, protoapigenone does not affect the ability of Rta to activate a promoter that contains an Rta-response element, showing that the inhibition is unrelated to Rta. Furthermore, in a lactate dehydrogenase assay, protoapigenone is not toxic to P3HR1 cells at the concentrations that inhibit the function of Zta, showing that protoapigenone is valuable for studying the function of Zta and preventing EBV lytic proliferation.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.031609-0
2011-08-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/92/8/1760.html?itemId=/content/journal/jgv/10.1099/vir.0.031609-0&mimeType=html&fmt=ahah

References

  1. Adamson A. L., Darr D., Holley-Guthrie E., Johnson R. A., Mauser A., Swenson J., Kenney S. 2000; Epstein-Barr virus immediate–early proteins BZLF1 and BRLF1 activate the ATF2 transcription factor by increasing the levels of phosphorylated p38 and c-Jun N-terminal kinases. J Virol 74:1224–1233 [View Article][PubMed]
    [Google Scholar]
  2. Chang F. R., Wei J. L., Teng C. M., Wu Y. C. 1998a; Antiplatelet aggregation constituents from Annona purpurea . J Nat Prod 61:1457–1461 [View Article][PubMed]
    [Google Scholar]
  3. Chang P. J., Chang Y. S., Liu S. T. 1998b; Role of Rta in the translation of bicistronic BZLF1 of Epstein-Barr virus. J Virol 72:5128–5136[PubMed]
    [Google Scholar]
  4. Chang L. K., Wei T. T., Chiu Y. F., Tung C. P., Chuang J. Y., Hung S. K., Li C., Liu S. T. 2003; Inhibition of Epstein-Barr virus lytic cycle by (−)-epigallocatechin gallate. Biochem Biophys Res Commun 301:1062–1068 [View Article][PubMed]
    [Google Scholar]
  5. Chang Y., Chang S. S., Lee H. H., Doong S. L., Takada K., Tsai C. H. 2004; Inhibition of the Epstein-Barr virus lytic cycle by Zta-targeted RNA interference. J Gen Virol 85:1371–1379 [View Article][PubMed]
    [Google Scholar]
  6. Chang L. K., Chung J. Y., Hong Y. R., Ichimura T., Nakao M., Liu S. T. 2005; Activation of Sp1-mediated transcription by Rta of Epstein–Barr virus via an interaction with MCAF1. Nucleic Acids Res 33:6528–6539 [View Article][PubMed]
    [Google Scholar]
  7. Chang H. L., Wu Y. C., Su J. H., Yeh Y. T., Yuan S. S. 2008a; Protoapigenone, a novel flavonoid, induces apoptosis in human prostate cancer cells through activation of p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase 1/2. J Pharmacol Exp Ther 325:841–849 [View Article][PubMed]
    [Google Scholar]
  8. Chang L. K., Liu S. T., Kuo C. W., Wang W. H., Chuang J. Y., Bianchi E., Hong Y. R. 2008b; Enhancement of transactivation activity of Rta of Epstein–Barr virus by RanBPM. J Mol Biol 379:231–242 [View Article][PubMed]
    [Google Scholar]
  9. Chang F. R., Hsieh Y. C., Chang Y. F., Lee K. H., Wu Y. C., Chang L. K. 2010a; Inhibition of the Epstein-Barr virus lytic cycle by moronic acid. Antiviral Res 85:490–495 [View Article][PubMed]
    [Google Scholar]
  10. Chang L. K., Chuang J. Y., Nakao M., Liu S. T. 2010b; MCAF1 and synergistic activation of the transcription of Epstein-Barr virus lytic genes by Rta and Zta. Nucleic Acids Res 38:4687–4700 [View Article][PubMed]
    [Google Scholar]
  11. Chen L. W., Chang P. J., Delecluse H. J., Miller G. 2005; Marked variation in response of consensus binding elements for the Rta protein of Epstein-Barr virus. J Virol 79:9635–9650 [View Article][PubMed]
    [Google Scholar]
  12. Chen Y. H., Chang F. R., Wu C. C., Yen M. H., Liaw C. C., Huang H. C., Kuo Y. H., Wu Y. C. 2006; New cytotoxic 6-oxygenated 8,9-dihydrofurocoumarins, hedyotiscone A–C, from Hedyotis biflora . Planta Med 72:75–78 [View Article][PubMed]
    [Google Scholar]
  13. Chen Y. L., Lan Y. H., Hsieh P. W., Wu C. C., Chen S. L., Yen C. T., Chang F. R., Hung W. C., Wu Y. C. 2008; Bioactive cembrane diterpenoids of Anisomeles indica . J Nat Prod 71:1207–1212 [View Article][PubMed]
    [Google Scholar]
  14. Chen W. Y., Hsieh Y. A., Tsai C. I., Kang Y. F., Chang F. R., Wu Y. C., Wu C. C. 2010; Protoapigenone, a natural derivative of apigenin, induces mitogen-activated protein kinase-dependent apoptosis in human breast cancer cells associated with induction of oxidative stress and inhibition of glutathione S-transferase pi. Invest New Drugs (Epub ahead of print) [View Article][PubMed]
    [Google Scholar]
  15. Chevallier-Greco A., Manet E., Chavrier P., Mosnier C., Daillie J., Sergeant A. 1986; Both Epstein-Barr virus (EBV)-encoded trans-acting factors, EB1 and EB2, are required to activate transcription from an EBV early promoter. EMBO J 5:3243–3249[PubMed]
    [Google Scholar]
  16. Chiu Y. F., Tung C. P., Lee Y. H., Wang W. H., Li C., Hung J. Y., Wang C. Y., Kawaguchi Y., Liu S. T. 2007; A comprehensive library of mutations of Epstein Barr virus. J Gen Virol 88:2463–2472 [View Article][PubMed]
    [Google Scholar]
  17. Cox M. A., Leahy J., Hardwick J. M. 1990; An enhancer within the divergent promoter of Epstein-Barr virus responds synergistically to the R and Z transactivators. J Virol 64:313–321[PubMed]
    [Google Scholar]
  18. Datta A. K., Feighny R. J., Pagano J. S. 1980; Induction of Epstein-Barr virus-associated DNA polymerase by 12-O-tetradecanoylphorbol-13-acetate. Purification and characterization. J Biol Chem 255:5120–5125[PubMed]
    [Google Scholar]
  19. Feederle R., Kost M., Baumann M., Janz A., Drouet E., Hammerschmidt W., Delecluse H. J. 2000; The Epstein-Barr virus lytic program is controlled by the co-operative functions of two transactivators. EMBO J 19:3080–3089 [View Article][PubMed]
    [Google Scholar]
  20. Fenton M., Sinclair A. J. 1999; Divergent requirements for the MAPK(ERK) signal transduction pathway during initial virus infection of quiescent primary B cells and disruption of Epstein-Barr virus latency by phorbol esters. J Virol 73:8913–8916[PubMed]
    [Google Scholar]
  21. Flemington E., Speck S. H. 1990; Autoregulation of Epstein-Barr virus putative lytic switch gene BZLF1. J Virol 64:1227–1232[PubMed]
    [Google Scholar]
  22. Gao X., Ikuta K., Tajima M., Sairenji T. 2001; 12-O-tetradecanoylphorbol-13-acetate induces Epstein-Barr virus reactivation via NF-κB and AP-1 as regulated by protein kinase C and mitogen-activated protein kinase. Virology 286:91–99 [View Article][PubMed]
    [Google Scholar]
  23. Giot J. F., Mikaelian I., Buisson M., Manet E., Joab I., Nicolas J. C., Sergeant A. 1991; Transcriptional interference between the EBV transcription factors EB1 and R: both DNA-binding and activation domains of EB1 are required. Nucleic Acids Res 19:1251–1258 [View Article][PubMed]
    [Google Scholar]
  24. Henle G., Henle W. 1970; Observations on childhood infections with the Epstein-Barr virus. J Infect Dis 121:303–310 [View Article][PubMed]
    [Google Scholar]
  25. Jones J. F., Shurin S., Abramowsky C., Tubbs R. R., Sciotto C. G., Wahl R., Sands J., Gottman D., Katz B. Z., Sklar J. 1988; T-cell lymphomas containing Epstein–Barr viral DNA in patients with chronic Epstein-Barr virus infections. N Engl J Med 318:733–741 [View Article][PubMed]
    [Google Scholar]
  26. Lee C. L., Chang F. R., Hsieh P. W., Chiang M. Y., Wu C. C., Huang Z. Y., Lan Y. H., Chen M., Lee K. H., Yen H.-F. 2008a; Cytotoxic ent-abietane diterpenes from Gelonium aequoreum . Phytochemistry 69:276–287 [View Article][PubMed]
    [Google Scholar]
  27. Lee Y. H., Chiu Y. F., Wang W. H., Chang L. K., Liu S. T. 2008b; Activation of the ERK signal transduction pathway by Epstein-Barr virus immediate–early protein Rta. J Gen Virol 89:2437–2446 [View Article][PubMed]
    [Google Scholar]
  28. Lin J. C. 2003; Mechanism of action of glycyrrhizic acid in inhibition of Epstein–Barr virus replication in vitro . Antiviral Res 59:41–47 [View Article][PubMed]
    [Google Scholar]
  29. Lin A. S., Nakagawa-Goto K., Chang F. R., Yu D., Morris-Natschke S. L., Wu C. C., Chen S. L., Wu Y. C., Lee K. H. 2007; First total synthesis of protoapigenone and its analogues as potent cytotoxic agents. J Med Chem 50:3921–3927 [View Article][PubMed]
    [Google Scholar]
  30. Lin T. P., Chen S. Y., Duh P. D., Chang L. K., Liu Y. N. 2008; Inhibition of the Epstein–Barr virus lytic cycle by andrographolide. Biol Pharm Bull 31:2018–2023 [View Article][PubMed]
    [Google Scholar]
  31. Luka J., Kallin B., Klein G. 1979; Induction of the Epstein–Barr virus (EBV) cycle in latently infected cells by n-butyrate. Virology 94:228–231 [View Article][PubMed]
    [Google Scholar]
  32. Miller G., El-Guindy A., Countryman J., Ye J., Gradoville L. 2007; Lytic cycle switches of oncogenic human gammaherpesviruses. Adv Cancer Res 97:81–109 [View Article][PubMed]
    [Google Scholar]
  33. Naranatt P. P., Akula S. M., Zien C. A., Krishnan H. H., Chandran B. 2003; Kaposi’s sarcoma-associated herpesvirus induces the phosphatidylinositol 3-kinase-PKC-zeta-MEK-ERK signaling pathway in target cells early during infection: implications for infectivity. J Virol 77:1524–1539 [View Article][PubMed]
    [Google Scholar]
  34. Ryan J. L., Fan H., Glaser S. L., Schichman S. A., Raab-Traub N., Gulley M. L. 2004; Epstein–Barr virus quantitation by real-time PCR targeting multiple gene segments: a novel approach to screen for the virus in paraffin-embedded tissue and plasma. J Mol Diagn 6:378–385 [View Article][PubMed]
    [Google Scholar]
  35. Schepers A., Pich D., Hammerschmidt W. 1996; Activation of oriLyt, the lytic origin of DNA replication of Epstein–Barr virus, by BZLF1. Virology 220:367–376 [View Article][PubMed]
    [Google Scholar]
  36. Wang Y., Prywes R. 2000; Activation of the c-fos enhancer by the erk MAP kinase pathway through two sequence elements: the c-fos AP-1 and p62TCF sites. Oncogene 19:1379–1385 [View Article][PubMed]
    [Google Scholar]
  37. Wang Y. C., Huang J. M., Montalvo E. A. 1997; Characterization of proteins binding to the ZII element in the Epstein-Barr virus BZLF1 promoter: transactivation by ATF1. Virology 227:323–330 [View Article][PubMed]
    [Google Scholar]
  38. Weiss L. M., Movahed L. A., Warnke R. A., Sklar J. 1989; Detection of Epstein-Barr viral genomes in Reed-Sternberg cells of Hodgkin’s disease. N Engl J Med 320:502–506 [View Article][PubMed]
    [Google Scholar]
  39. Wolf H., zur Hausen H., Becker V. 1973; EB viral genomes in epithelial nasopharyngeal carcinoma cells. Nat New Biol 244:245–247[PubMed] [CrossRef]
    [Google Scholar]
  40. Yajima T., Yagihashi A., Kameshima H., Furuya D., Kobayashi D., Hirata K., Watanabe N. 2000; Establishment of quantitative reverse transcription–polymerase chain reaction assays for human telomerase-associated genes. Clin Chim Acta 290:117–127 [View Article][PubMed]
    [Google Scholar]
  41. Yiu C. Y., Chen S. Y., Chang L. K., Chiu Y. F., Lin T. P. 2010; Inhibitory effects of resveratrol on the Epstein–Barr virus lytic cycle. Molecules 15:7115–7124 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.031609-0
Loading
/content/journal/jgv/10.1099/vir.0.031609-0
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
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