1887

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus-8-encoded viral interferon regulatory factor (vIRF) transforms NIH3T3 cells, represses interferon signal transduction and regulates the expression of other KSHV genes. Here, we have shown that vIRF is a transcriptional activator and auto-activates its own expression. Ectopic expression of vIRF activated the vIRF promoter in KSHV-negative 293, COS7, HeLa and BJAB cell lines in a dose-dependent fashion in a reporter assay and the expression of vIRF transcripts from endogenous viral genomes in BCBL-1 and BC-1 cells latently infected with KSHV. Deletion analysis identified two elements, named and , in the vIRF promoter that were responsive to vIRF activation. vIRF auto-activation via but not was repressed by , a transcriptional silencer in the vIRF promoter. Neither nor contain any interferon-stimulated response element (ISRE)-like sequences and are unresponsive to induction with interferon-β and -γ. These results indicate that KSHV uses the mechanism of auto-activation to regulate the expression of a viral transforming protein to efficiently evade host tumour suppressor pathways.

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2003-02-01
2020-12-04
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References

  1. Ausubel F. M., Brent R., Kingston R. E., Moore D. D., Seidman J. G., Smith J. A., Struhl K.. (editors) 1995; Current Protocols in Molecular Biology . New York: John Wiley;
  2. Boshoff C., Whitby D., Hatziionnou T., Fisher C., van der Walt J., Hatzakis A., Weiss R., Schulz T.. 1995; Kaposi's sarcoma-associated herpesvirus in HIV-negative Kaposi's sarcoma. Lancet345:1043–1044
    [Google Scholar]
  3. Burysek L., Yeow W. S., Lubyova B., Kellum M., Schafer S. L., Huang Y. Q., Pitha P. M.. 1999; Functional analysis of human herpesvirus 8-encoded viral interferon regulatory factor 1 and its association with cellular interferon regulatory factors and p300. J Virol73:7334–7342
    [Google Scholar]
  4. Carbone A., Gloghini A., Vaccher E.. 8 other authors 1996; Kaposi's sarcoma-associated herpesvirus DNA sequences in AIDS-related and AIDS-unrelated lymphomatous effusions. Br J Haematol94:533–543
    [Google Scholar]
  5. Cesarman E., Chang Y., Moore P. S., Said J. W., Knowles D. M.. 1995a; Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med332:1186–1191
    [Google Scholar]
  6. Cesarman E., Moore P. S., Rao P. H., Inghirami G., Knowles D. M., Chang Y.. 1995b; In vitro establishment and characterization of two acquired immunodeficiency syndrome-related lymphoma cell lines (BC-1 and BC-2) containing Kaposi's sarcoma-associated herpesvirus-like (KSHV) DNA sequences. Blood86:2708–2714
    [Google Scholar]
  7. 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. Science266:1865–1869
    [Google Scholar]
  8. Chang Y., Ziegler J., Wabinga H.. 8 other authors 1996; Kaposi's sarcoma-associated herpesvirus and Kaposi's sarcoma in Africa. Uganda Kaposi's Sarcoma Study Group.. Arch Intern Med156:202–204
    [Google Scholar]
  9. Darnell J. E. Jr, Kerr I. M., Stark G. R.. 1994; Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science264:1415–1421
    [Google Scholar]
  10. Deng H., Young A., Sun R.. 2000; Auto-activation of the rta gene of human herpesvirus-8/Kaposi's sarcoma-associated herpesvirus. J Gen Virol81:3043–3048
    [Google Scholar]
  11. Dupin N., Grandadam M., Calvez V.. 8 other authors 1995; Herpesvirus-like DNA in patients with Mediterranean Kaposi's sarcoma. Lancet345:761–762
    [Google Scholar]
  12. Flemington E., Speck S. H.. 1990; Autoregulation of Epstein–Barr virus putative lytic switch gene BZLF1. J Virol64:1227–1232
    [Google Scholar]
  13. Fujita T., Kimura Y., Miyamoto M., Barsoumian E. L., Taniguchi T.. 1989; Induction of endogenous IFN-alpha and IFN-beta genes by a regulatory transcription factor, IRF-1. Nature337:270–272
    [Google Scholar]
  14. Gao S. J., Boshoff C., Jayachandra S., Weiss R. A., Chang Y., Moore P. S.. 1997; KSHV ORF K9 (vIRF) is an oncogene which inhibits the interferon signaling pathway. Oncogene15:1979–1985
    [Google Scholar]
  15. Gessain A., Sudaka A., Briere J.. 8 other authors 1996; Kaposi sarcoma-associated herpes-like virus (human herpesvirus type 8) DNA sequences in multicentric Castleman's disease: is there any relevant association in non-human immunodeficiency virus-infected patients?. Blood87:414–416
    [Google Scholar]
  16. Harada H., Fujita T., Miyamoto M., Kimura Y., Maruyama M., Furia A., Miyata T., Taniguchi T.. 1989; Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes. Cell58:729–739
    [Google Scholar]
  17. Imam A. M., Ackrill A. M., Dale T. C., Kerr I. M., Stark G. R.. 1990; Transcription factors induced by interferons alpha and gamma. Nucleic Acids Res18:6573–6580
    [Google Scholar]
  18. Jayachandra S., Low K. G., Thlick A. E., Yu J., Ling P. D., Chang Y., Moore P. S.. 1999; Three unrelated viral transforming proteins (vIRF, EBNA2 and E1A) induce the MYC oncogene through the interferon-responsive PRF element by using different transcription coadaptors. Proc Natl Acad Sci U S A96:11566–11571
    [Google Scholar]
  19. Karcher D. S., Alkan S.. 1995; Herpes-like DNA sequences, AIDS-related tumors, and Castleman's disease. N Engl J Med333:797–798
    [Google Scholar]
  20. Li M., Lee H., Guo J., Neipel F., Fleckenstein B., Ozato K., Jung J. U.. 1998; Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor. J Virol72:5433–5440
    [Google Scholar]
  21. Li M., Damania B., Alvarez X., Ogryzko V., Ozato K., Jung J. U.. 2000; Inhibition of p300 histone acetyltransferase by viral interferon regulatory factor. Mol Cell Biol20:8254–8263
    [Google Scholar]
  22. Lin R., Genin P., Mamane Y., Sgarbanti M., Battistini A., Harrington W. J. Jr, Barber G. N., Hiscott J.. 2001; HHV-8 encoded vIRF-1 represses the interferon antiviral response by blocking IRF-3 recruitment of the CBP/p300 coactivators. Oncogene20:800–811
    [Google Scholar]
  23. Moore P. S., Chang Y.. 1995; Detection of herpesvirus-like DNA sequences in Kaposi's sarcoma lesions from persons with and without HIV infection. N Engl J Med332:1181–1185
    [Google Scholar]
  24. Nador R. G., Cesarman E., Knowles D. M., Said J. W.. 1995; Herpes-like DNA sequences in a body-cavity-based lymphoma in an HIV-negative patient. N Engl J Med333:943
    [Google Scholar]
  25. Nakamura H., Li M., Zarycki J., Jung J. U.. 2001; Inhibition of p53 tumor suppressor by viral interferon regulatory factor. J Virol75:7572–7582
    [Google Scholar]
  26. Nguyen H., Mustafa A., Hiscott J., Lin R.. 1995; Transcription factor IRF-2 exerts its oncogenic phenotype through the DNA binding/transcription repression domain. Oncogene11:537–544
    [Google Scholar]
  27. Pastore C., Gloghini A., Volpe G., Nomdedeu J., Leonardo E., Mazza U., Saglio G., Carbone A., Gaidano G.. 1995; Distribution of Kaposi's sarcoma herpesvirus sequences among lymphoid malignancies in Italy and Spain. Br J Haematol91:918–920
    [Google Scholar]
  28. Pine R., Decker T., Kessler D. S., Levy D. E., Darnell J. J.. 1990; Purification and cloning of interferon-stimulated gene factor 2 (ISGF2): ISGF2 (IRF-1) can bind to the promoters of both beta interferon- and interferon-stimulated genes but is not a primary transcriptional activator of either. Mol Cell Biol10:2448–2457
    [Google Scholar]
  29. Ragoczy T., Miller G.. 2001; Autostimulation of the Epstein–Barr virus BRLF1 promoter is mediated through consensus Sp1 and Sp3 binding sites. J Virol75:5240–5251
    [Google Scholar]
  30. 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. Nature Med2:342–346
    [Google Scholar]
  31. Roan F., Zimring J. C., Goodbourn S., Offermann M. K.. 1999; Transcriptional activation by the human herpesvirus-8-encoded interferon regulatory factor. J Gen Virol80:2205–2209
    [Google Scholar]
  32. 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 A93:14862–14867
    [Google Scholar]
  33. Schalling M., Ekman M., Kaaya E. E., Linde A., Biberfeld P.. 1995; A role for a new herpesvirus (KSHV) in different forms of Kaposi's sarcoma. Nature Med1:707–708
    [Google Scholar]
  34. Seo T., Lee D., Lee B., Chung J. H., Choe J.. 2000; Viral interferon regulatory factor 1 of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) binds to, and inhibits transactivation of, CREB-binding protein. Biochem Biophys Res Commun270:23–27
    [Google Scholar]
  35. Seo T., Park J., Lee D., Hwang S. G., Choe J.. 2001; Viral interferon regulatory factor 1 of Kaposi's sarcoma-associated herpesvirus binds to p53 and represses p53-dependent transcription and apoptosis. J Virol75:6193–6198
    [Google Scholar]
  36. Soulier J., Grollet L., Oksenhendler E.. 7 other authors 1995; Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease. Blood86:1276–1280
    [Google Scholar]
  37. Taniguchi T.. 1995; IRF-1 and IRF-2 as regulators of the interferon system and cell growth. Indian J Biochem Biophys32:235–239
    [Google Scholar]
  38. Taniguchi T., Tanaka N., Taki S.. 1998; Regulation of the interferon system, immune response and oncogenesis by the transcription factor interferon regulatory factor-1. Eur Cytokine Netw9:43–48
    [Google Scholar]
  39. Wang X., Zhang Y., Deng J., Pan H., Zhou F., Montalvo E. A., Gao S. J.. 2001; Characterization of the promoter region of viral interferon regulatory factor encoded by Kaposi's sarcoma-associated herpesvirus. Oncogene20:523–530
    [Google Scholar]
  40. Wang X. P., Zhang Y. J., Deng J. H., Pan H. Y., Zhou F. C., Gao S. J.. 2002; Transcriptional regulation of Kaposi's sarcoma-associated herpesvirus-encoded oncogene viral interferon regulatory factor by a novel transcriptional silencer, Tis. J Biol Chem277:12023–12031
    [Google Scholar]
  41. Zimring J. C., Goodbourn S., Offermann M. K.. 1998; Human herpesvirus 8 encodes an interferon regulatory factor (IRF) homolog that represses IRF-1-mediated transcription. J Virol72:701–707
    [Google Scholar]
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