1887

Abstract

Herpesvirus saimiri (HVS) ORF 57 is homologous to genes identified in all classes of herpesviruses. We have previously shown that ORF 57 encodes a multifunctional protein, responsible for both transactivation and repression of viral gene expression at a post-transcriptional level. This suggests that the ORF 57 protein shares some functional similarities with the herpes simplex virus IE63/ICP27 and Epstein–Barr virus Mta proteins. However, little is known about the functional domains responsible for the properties of ORF 57 due to the limited homology shared between these proteins. In this report, we have identified the functional domains responsible for transactivation and repression by the ORF 57 protein. We demonstrate that the carboxy terminus is required for ORF 57 transactivation, repression and an intense SC-35 nuclear spotting. This region contains two highly conserved motifs amongst its homologues, a zinc finger-like motif and a highly hydrophobic domain. We further show that the hydrophobic domain is required for transactivation and is also involved in nuclear localization of the ORF 57 protein, whereas the zinc finger-like domain is required for transactivation, repression and the intense SC-35 nuclear spotting.

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2000-09-01
2019-10-14
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References

  1. Albrecht, J. C., Nicholas, J., Biller, D., Cameron, K. R., Biesinger, B., Newman, C., Wittman, S., Craxton, M. A., Coleman, H., Fleckenstein, B. & Honess, R. W. ( 1992; ). Primary structure of the herpesvirus saimiri genome. Journal of Virology 66, 5047-5058.
    [Google Scholar]
  2. Bello, L. J., Davison, A. J., Glenn, M., Whitehouse, A., Rethmeier, N., Schulz, T. F. & Clements, J. B. ( 1999; ). The human herpesvirus-8 ORF 57 gene and its properties. Journal of General Virology 80, 3207-3215.
    [Google Scholar]
  3. Boyle, S. M., Ruvolo, V., Gupta, A. K. & Swaminathan, S. ( 1999; ). Association of the cellular export receptor CRM 1 mediates function and intracellular localization of the Epstein–Barr virus SM protein, a regulator of gene expression. Journal of Virology 73, 6872-6881.
    [Google Scholar]
  4. Brown, C. R., Nakamura, M. S., Mosca, J. D., Hayward, G. S., Straus, S. E. & Perera, L. P. ( 1995; ). Herpes simplex virus trans-regulatory protein ICP27 stabilizes and binds to 3′ ends of labile mRNA. Journal of Virology 69, 7187-7195.
    [Google Scholar]
  5. Cooper, M., Goodwin, D. J., Hall, K. T., Stevenson, A. J., Meredith, D. M., Markham, A. F. & Whitehouse, A. ( 1999; ). The gene product encoded by ORF 57 of herpesvirus saimiri regulates the redistribution of the splicing factor, SC-35. Journal of General Virology 80, 1311-1316.
    [Google Scholar]
  6. Fleckenstein, B. & Desrosiers, R. C. ( 1982; ). Herpesvirus saimiri and herpesvirus ateles. In The Herpesviruses, pp. 253-332. Edited by B. Roizman. New York: Plenum Press.
  7. Goodwin, D. J., Hall, K. T., Stevenson, A. J., Markham, A. F. & Whitehouse, A. ( 1999; ). The ORF 57 protein of herpesvirus saimiri shuttles between the nucleus and cytoplasm and is involved in viral RNA nuclear export. Journal of Virology 73, 10519-10524.
    [Google Scholar]
  8. Gorman, C. M., Moffat, L. F. & Howard, B. H. ( 1982; ). Recombinant genomes which express chloramphenicol acetyl-transferase in mammalian cells. Molecular and Cellular Biology 2, 1044-1051.
    [Google Scholar]
  9. Hall, K. T., Stevenson, A. J., Goodwin, D. J., Gibson, P. C., Markham, A. F. & Whitehouse, A. ( 1999; ). The activation domain of the herpesvirus saimiri R protein interacts with the TATA-binding protein. Journal of Virology 73, 9756-9763.
    [Google Scholar]
  10. Hardwicke, M. A. & Sandri-Goldin, R. M. ( 1994; ). The herpes simplex virus regulatory protein ICP27 contributes to the decrease in cellular mRNA levels during infection. Journal of Virology 68, 4797-4810.
    [Google Scholar]
  11. Hardwicke, M. A., Vaughan, P. J., Sekulovich, R. E., O’Connor, R. & Sandri-Goldin, R. M. ( 1989; ). The regions important for the activator and repressor functions of the herpes simplex virus alpha protein ICP27 map to the C-terminal half of the protein. Journal of Virology 63, 4590-4602.
    [Google Scholar]
  12. Hardy, W. R. & Sandri-Goldin, R. M. ( 1994; ). Herpes simplex virus inhibits host cell splicing, and the regulatory protein ICP27 is required for this effect. Journal of Virology 68, 7790-7799.
    [Google Scholar]
  13. Hibbard, M. K. & Sandri-Goldin, R. M. ( 1995; ). Arginine-rich regions succeeding the nuclear localization region of herpes simplex virus type 1 regulatory protein ICP27 are required for efficient nuclear localization and late gene expression. Journal of Virology 69, 4656-4667.
    [Google Scholar]
  14. Kenney, S., Holley-Guthrie, E. A., Mar, E.-C. & Smith, M. ( 1989; ). The Epstein-Barr virus BMLF1 promoter contains an enhancer element that is responsive to the BZLF1 and BRLF1 transactivators. Journal of Virology 63, 3878-3883.
    [Google Scholar]
  15. 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]
  16. McMahan, L. & Schaffer, P. A. ( 1990; ). The repressing and enhancing functions of the herpes simplex virus regulatory protein ICP27 map to the C terminal regions and are required to modulate viral gene expression very early in infection. Journal of Virology 64, 3471-3485.
    [Google Scholar]
  17. Mears, W. E. & Rice, S. A. ( 1996; ). The RGG box of the herpes simplex virus ICP27 protein mediates RNA binding activity and determines in vivo methylation. Journal of Virology 70, 7445-7453.
    [Google Scholar]
  18. Mears, W. E., Lam, V. & Rice, S. A. ( 1995; ). Identification of nuclear and nucleolar localization signal sequences in the herpes simplex virus regulatory protein ICP27. Journal of Virology 69, 935-947.
    [Google Scholar]
  19. Neipel, F., Albrecht, J. C. & Fleckenstein, B. ( 1997; ). Cell-homologous genes in Kaposi’s sarcoma associated rhadinovirus human herpesvirus 8: determinants of its pathogenicity? Journal of Virology 71, 4187-4192.
    [Google Scholar]
  20. Nicholas, J., Gompels, U. A., Craxton, M. A. & Honess, R. W. ( 1988; ). Conservation of sequence and function between the product of the 52-kilodalton immediate-early gene of the herpesvirus saimiri and the BMLF1-encoded transcriptional effector (EB2) of the Epstein–Barr virus. Journal of Virology 62, 3250-3257.
    [Google Scholar]
  21. Nicholas, J., Coles, L. S., Newman, C. & Honess, R. W. ( 1991; ). Regulation of the herpesvirus saimiri (HVS) delayed-early 110-kilodalton promoter by HVS immediate-early gene products and a homolog of the Epstein–Barr virus R transactivator. Journal of Virology 65, 2457-2466.
    [Google Scholar]
  22. Perera, L. P., Kaushal, S., Kinchington, P. R., Mosca, J. D., Hayward, G. S. & Straus, S. E. ( 1994; ). Varicella-zoster virus open reading frame 4 encodes a transcriptional activator that is functionally distinct from that of herpes simplex virus homolog ICP27. Journal of Virology 68, 2468-2477.
    [Google Scholar]
  23. Phelan, A. & Clements, J. B. ( 1998; ). Posttranscriptional regulation in herpes simplex virus. Seminars in Virology 8, 309-318.[CrossRef]
    [Google Scholar]
  24. Ragoczy, T., Heston, L. & Miller, G. ( 1998; ). The Epstein–Barr virus Rta protein activates lytic cycle genes and can disrupt latency in B lymphocytes. Journal of Virology 72, 7978-7984.
    [Google Scholar]
  25. Randall, R. E., Honess, R. W. & O’Hare, P. ( 1983; ). Proteins specified by herpesvirus saimiri: identification and properties in virus-specific polypeptides in productively infected cells. Journal of General Virology 64, 19-35.[CrossRef]
    [Google Scholar]
  26. Rice, S. A. & Lam, V. ( 1994; ). Amino acid substitution mutations in the herpes simplex virus ICP27 protein define an essential regulation function. Journal of Virology 68, 823-833.
    [Google Scholar]
  27. Rice, S. A., Lam, V. & Knipe, D. M. ( 1993; ). The acidic amino-terminal region of herpes simplex virus type 1 α protein ICP27 is required for an essential gene regulation function. Journal of Virology 67, 1778-1787.
    [Google Scholar]
  28. Russo, J. J., Bohenzhy, R. A., Chein, M. C., Chen, J., Yan, M., Maddalena, D., Parry, J. P., Peruzzi, D., Edelman, I. S., Chang, Y. & Moore, P. S. ( 1996; ). Nucleotide sequences of the Kaposi sarcoma-associated herpesvirus (HHV8). Proceedings of the National Academy of Sciences, USA 93, 14862-14867.[CrossRef]
    [Google Scholar]
  29. Ruvolo, V., Wang, E., Boyle, S. & Swaminathan, S. ( 1998; ). The Epstein–Barr virus nuclear protein SM is both a post-transcriptional inhibitor and activator of gene expression. Proceedings of the National Academy of Sciences, USA 95, 8852-8857.[CrossRef]
    [Google Scholar]
  30. Sandri-Goldin, R. M. ( 1998; ). ICP27 mediates herpes simplex virus nuclear export by shuttling through a leucine rich nuclear export signal and binding viral intronless RNAs through an RGG motif. Genes & Development 12, 868-879.[CrossRef]
    [Google Scholar]
  31. Sandri-Goldin, R. M. & Hibbard, M. K. ( 1996; ). The herpes simplex virus type 1 regulatory protein ICP27 coimmunoprecipitates with anti-Sm anti-serum and the C-terminus appears to be required for this interaction. Journal of Virology 70, 108-118.
    [Google Scholar]
  32. Sandri-Goldin, R. M., Hibbard, M. K. & Hardwicke, M. A. ( 1995; ). The C-terminal repressor region of herpes simplex virus type 1 ICP27 is required for the redistribution of small nuclear ribonucleoprotein particles and splicing factor SC35; however, these alterations are not sufficient to inhibit host cell splicing. Journal of Virology 69, 6063-6076.
    [Google Scholar]
  33. Semmes, O. J., Chen, L., Sarisky, R. T., Gao, Z., Zhong, L. & Hayward, S. D. ( 1998; ). Mta has properties of an RNA export protein and increases cytoplasmic accumulation of Epstein–Barr virus replication gene mRNA. Journal of Virology 72, 9526-9534.
    [Google Scholar]
  34. Smith, I. L., Sekulovich, R. E., Hardwicke, M. A. & Sandri-Goldin, R. M. ( 1991; ). Mutations in the activation region of herpes simplex virus regulatory protein ICP27 can be trans dominant. Journal of Virology 65, 3656-3666.
    [Google Scholar]
  35. Sun, R., Lin, S. F., Gradoville, L., Yuan, Y., Zhu, F. & Miller, G. ( 1998; ). A viral gene that activates lytic cycle expression of the Kaposi’s sarcoma-associated herpesvirus. Proceedings of the National Academy of Sciences, USA 95, 10866-10871.[CrossRef]
    [Google Scholar]
  36. Vaughan, P. J., Thibault, K. J., Hardwicke, M. A. & Sandri-Goldin, R. M. ( 1992; ). The herpes simplex virus immediate early protein ICP27 encodes a potential metal binding domain and binds zinc in vitro. Virology 189, 377-384.[CrossRef]
    [Google Scholar]
  37. Virgin, H. W., Latreille, P., Wamsley, P., Hallsworth, K., Weck, K. E., Dal Canto, A. J. & Speck, S. H. ( 1997; ). Complete sequence and genomic analysis of murine gammaherpesvirus 68. Journal of Virology 71, 5894-5904.
    [Google Scholar]
  38. Wadd, S., Bryant, H., Filhol, O., Scott, J. E., Hsieh, T. S., Everett, R. D. & Clements, J. B. ( 1999; ). The multifunctional herpes simplex virus IE63 protein interacts with the heterogeneous ribonucleoprotein K and with casein kinase 2. Journal of Biological Chemistry 274, 28991-28998.[CrossRef]
    [Google Scholar]
  39. Whitehouse, A., Carr, I. M., Griffiths, J. C. & Meredith, D. M. ( 1997a; ). The herpesvirus saimiri ORF 50 gene, encoding a major transcriptional activator homologous to the Epstein–Barr virus R protein, is transcribed from two distinct promoters of different temporal phases. Journal of Virology 71, 2550-2554.
    [Google Scholar]
  40. Whitehouse, A., Stevenson, A. J., Cooper, M. & Meredith, D. M. ( 1997b; ). Identification of a cis-acting element within the herpesvirus saimiri ORF6 promoter that is responsive to the HVS.R transactivator. Journal of General Virology 78, 1411-1415.
    [Google Scholar]
  41. Whitehouse, A., Cooper, M., Hall, K. T. & Meredith, D. M. ( 1998a; ). The open reading frame (ORF) 50a gene product regulates ORF 57 gene expression in herpesvirus saimiri. Journal of Virology 72, 1967-1973.
    [Google Scholar]
  42. Whitehouse, A., Cooper, M. & Meredith, D. M. ( 1998b; ). The IE gene product encoded by ORF 57 of herpesvirus saimiri modulates gene expression at a post-transcriptional level. Journal of Virology 72, 857-861.
    [Google Scholar]
  43. Winkler, M., Rice, S. A. & Stamminger, T. ( 1994; ). UL69 of human cytomegalovirus, an open reading frame with homology to ICP27 of herpes simplex virus, encodes a transcriptional activator. Journal of Virology 68, 3943-3954.
    [Google Scholar]
  44. Zalani, S., Holley-Guthrie, E. & Kenney, S. ( 1996; ). Epstein–Barr viral latency is disrupted by the immediate-early BRLF1 protein through a cell-specific mechanism. Proceedings of the National Academy of Sciences, USA 93, 9194-9199.[CrossRef]
    [Google Scholar]
  45. Zhi, Y., Sciabica, K. S. & Sandri-Goldin, R. M. ( 1999; ). Self interaction of the herpes simplex type 1 regulatory protein ICP27. Virology 257, 341-351.[CrossRef]
    [Google Scholar]
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