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Abstract

Human herpesvirus-8 (HHV-8) is a lymphotropic virus associated with several AIDS-related neoplasms. Two ORFs play a critical role in the regulation of virus replication: ORF50, encoding an immediate-early transcriptional activator, and ORF57, encoding a post-transcriptional regulator. We analysed their effects on the activation of the human immunodeficiency virus type 1 (HIV-1) LTR. ORF50 interacted synergically with , inducing a 10-fold enhancement of HIV-1 LTR transactivation. This effect occurred both in BCBL-1 cells, latently infected with HHV-8, and in HL3T1 cells, an epithelial cell line non-permissive to HHV-8 infection. Also, ORF57 enhanced -induced transactivation of HIV-1 LTR, but only in BCBL-1 cells, suggesting that its action was likely mediated by the induction of other viral functions. Finally, when both ORFs were expressed, the enhancement of transactivation induced by ORF50 was partially inhibited. The findings suggest that ORF57 can modulate ORF50 activity and that ORF50 may render biologically active small amounts of .

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2001-08-01
2020-01-25
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References

  1. Bello, L. J., Davison, A. J., Glenn, M. A., Whitehouse, A., Rethmeier, N., Schulz, T. F. & Clements, J. B. ( 1999; ). The human herpesvirus-8 ORF57 gene and its properties. Journal of General Virology 80, 3207-3215.
    [Google Scholar]
  2. Biggar, R. J., Rosemberg, P. S. & Cotè, T. ( 1996; ). AIDS/cancer match study group. Kaposi’s sarcoma and non-Hodgkin’s lymphoma following the diagnosis of AIDS. International Journal of Cancer 68, 754-58.[CrossRef]
    [Google Scholar]
  3. Buisson, M., Manet, E., Trescol-Biemont, M. C., Gruffat, H., Durand, B. & Sergeant, A. ( 1989; ). The Epstein–Barr virus (EBV) early protein EB2 is a posttranscriptional activator expressed under the control of EBV transcription factors EB1 and R. Journal of Virology 63, 5276-5284.
    [Google Scholar]
  4. Caputo, A., Sodroski, J. G. & Haseltine, W. A. ( 1990; ). Constitutive expression of HIV-1 Tat protein in human Jurkat T cells using a BK virus vector. Journal of Acquired Immune Deficiency Syndromes 3, 372-379.
    [Google Scholar]
  5. Caputo, A., Grossi, M. P., Bozzini, R., Rossi, C., Betti, M., Marconi, P. C., Barbanti-Brodano, G. & Balboni, P. G. ( 1996; ). Inhibition of HIV-1 replication and reactivation from latency by tat transdominant negative mutants in the cysteine rich region. Gene Therapy 3, 235-245.
    [Google Scholar]
  6. Caputo, A., Betti, M., Boarini, C., Mantovani, I., Corallini, A. & Barbanti-Brodano, G. ( 1999; ). Multiple functions of human immunodeficiency virus type 1 Tat protein in the pathogenesis of AIDS. Recent Research and Development in Virology 1, 753-771.
    [Google Scholar]
  7. Cesarman, E., Chang, Y., Moore, P. S., Said, J. W. & Knowles, D. M. ( 1995; ). Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. New England Journal of Medicine 332, 1186-1191.[CrossRef]
    [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. Cooper, M., Goodwin, D. J., Hall, K. T., Stevenson, A. J., Meredith, D. M., Alexander, F. M. & Whitehouse, A. ( 1999; ). The gene product encoded by ORF57 of herpesvirus saimiri regulates the redistribution of the splicing factor SC-35. Journal of General Virology 80, 1311-1316.
    [Google Scholar]
  10. Davis, L. G., Dibner, M. D. & Battey, J. F. (editors) (1986). Basic Methods in Molecular Biology. New York: Elsevier Science Publishing.
  11. Grossi, M. P., Caputo, A., Rimessi, P., Chiccoli, L., Balboni, P. G. & Barbanti-Brodano, G. ( 1988; ). New BK virus episomal vector for complementary DNA expression in human cells. Archives of Virology 102, 275-283.[CrossRef]
    [Google Scholar]
  12. Harrington, W.Jr, Sieczkowski, L., Sosa, C., Chan-a-Sue, S., Cai, J. P., Cabral, L. & Wood, C. ( 1997; ). Activation of HHV-8 by HIV-1 Tat. Lancet 349, 774-775.
    [Google Scholar]
  13. Kirshner, J. R., Lukac, D., Chang, J. & Ganem, D. ( 2000; ). Kaposi’s sarcoma-associated herpesvirus open reading frame 57 encodes a posttranscriptional regulator with multiple distinct activities. Journal of Virology 74, 3586-3597.[CrossRef]
    [Google Scholar]
  14. Lukac, D. M., Renne, R., Kirshner, J. R. & Ganem, D. ( 1998; ). Reactivation of Kaposi’s sarcoma associated herpesvirus from latency by expression of the ORF50 transactivator, a homolog of the EBV R protein. Virology 282, 304-312.
    [Google Scholar]
  15. Lukac, D. N., Kirshner, J. R. & Ganem, D. ( 1999; ). Transcriptional activation by the product of open reading frame 50 of Kaposi’s sarcoma-associated herpesvirus is required for lytic viral reactivation in B cells. Journal of Virology 73, 9348-9361.
    [Google Scholar]
  16. Moir, S., Lapointe, R., Malaspina, A., Ostrowski, M., Cole, C. E., Chun, T-W., Adelsberger, J., Baseler, M., Hwu, P. & Fauci, A. S. ( 1999; ). CD40-mediated induction of CD4 and XCXCR4 on B lymphocytes correlates with restricted susceptibility to human immunodeficiency virus type 1 infection: potential role of B lymphocytes as a viral reservoir. Journal of Virology 73, 7072-7980.
    [Google Scholar]
  17. Moir, S., Malaspina, A., Li, Y., Chun, T-W., Lowe, T., Adelsberger, J., Baseler, M., Ehler, L. A., Liu, S., Davey, R. T., Mican, J. A. & Fauci, A. S. ( 2000; ). B cells of HIV-1-infected patients binds virions through CD21-complement interactions and transmit infectious virus to activated T cells. Journal of Experimental Medicine 192, 637-646.[CrossRef]
    [Google Scholar]
  18. Monini, P., Colombini, S., Sturzl, M., Goletti, D., Cafaro, A., Sgadari, C., Butto, S., Franco, M., Leone, P., Fais, S., Leone, P., Melucci-Vigo, G., Chiozzini, C., Carlini, F., Ascherl, G., Cornali, E., Zietz, C., Ramazotti, E., Ensoli, F., Andreoni, M., Pezzotti, P., Reza, G., Yarchoan, R, Gallo, R. C. & Ensoli, B. ( 1999; ). Reactivation and persistence of human herpesvirus-8 infection in B cells and monocytes by Th-1 cytokines increased in Kaposi’s sarcoma. Blood 93, 4044-4058.
    [Google Scholar]
  19. Moore, A. Y., Hudnale, S. D., Rady, P. L., Wagner, R. F., Moore, T. O.Jr, Memar, O., Hughes, T. K. & Tyring, S. K. ( 2000; ). Differential expression of the HHV-8 vGCR cellular homolog gene in AIDS-associated and classic Kaposi’s sarcoma: potential role of HIV-1 Tat. Virology 267, 247-251.[CrossRef]
    [Google Scholar]
  20. Okamoto, H., Sheline, C. T., Corden, J. L., Jones, K. A. & Peterlin, B. M. ( 1996; ). Trans-activation by human immunodeficiency virus Tat protein requires the C-terminal domain of RNA polymerase II. Proceedings of the National Academy of Sciences, USA 93, 11575-11579.[CrossRef]
    [Google Scholar]
  21. 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 Medicine 2, 342-346.[CrossRef]
    [Google Scholar]
  22. Schulz, T. ( 1998; ). Kaposi’s sarcoma-associated herpesvirus (human herpesvirus-8). Journal of General Virology 79, 1573-1591.
    [Google Scholar]
  23. Soulier, J., Grollet, L., Oksenhendler, E., Cacoub, P., Cazals-Hatem, D., Babinet, P., d’Agay, M. F., Clauvel, J. P., Raphael, M., Degos, L. & Sigaux, F. ( 1995; ). Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman’s disease. Blood 86, 1276-1280.
    [Google Scholar]
  24. Staskus, K. A., Zhong, W., Gebhard, K., Herndier, B., Wang, H., Renne, R., Beneke, J., Pudney, J., Anderson, D. J., Ganem, D. & Haase, A. T. ( 1997; ). Kaposi’s sarcoma-associated herpesvirus gene expression in endothelial (spindle) tumor cells. Journal of Virology 71, 715-719.
    [Google Scholar]
  25. Varthakavi, V., Browning, P. J. & Spearman, P. ( 1999; ). Human immunodeficiency virus replication in a primary effusion lymphoma cell line stimulate lytic-phase replication of Kaposi’s sarcoma-associated herpesvirus. Journal of Virology 73, 10329-10338.
    [Google Scholar]
  26. Whitby, D., Howard, M. R., Tenant-Flowers, M., Brink, N. S., Copas, A., Boshoff, C., Hatzioannou, T., Suggett, F. E., Aldam, D. M., Denton, A. S. and others ( 1995; ). Detection of Kaposi’s sarcoma associated herpesvirus in peripheral blood of HIV-infected individuals and progression to Kaposi’s sarcoma. Lancet 346, 799–802.[CrossRef]
    [Google Scholar]
  27. Whitehouse, A., Cooper, M., Hall, K. T. & Meredith, D. M. ( 1998a; ). The open reading frame (ORF) 50a gene product regulates ORF57 gene expression in herpesvirus saimiri. Journal of Virology 72, 1967-1973.
    [Google Scholar]
  28. Whitehouse, A., Cooper, M. & Meredith, D. M. ( 1998b; ). The immediate-early gene product encoded by open reading frame 57 of herpesvirus saimiri modulates gene expression at a posttranscriptional level. Journal of Virology 72, 857-861.
    [Google Scholar]
  29. Wright, C. M., Felber, B. K., Paskalis, H. & Pavlakis, G. N. ( 1986; ). Expression and characterization of the trans-activator of HTLV-III/LAV virus. Science 234, 988-992.[CrossRef]
    [Google Scholar]
  30. Zhou, Q., Chen, D., Pierstorff, E. & Luo, K. ( 1998; ). Transcription elongation factor P-TEFb mediates Tat activation of HIV-1 transcription at multiple stages. EMBO Journal 17, 3681-3691.[CrossRef]
    [Google Scholar]
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