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1887

Journal of General Virology header logo Journal of General Virology

Volume 86, Issue 3

The herpesvirus saimiri Rta gene autostimulates via binding to a non-consensus response element No Access

Abstract

Herpesvirus saimiri ORF 50a protein expression is sufficient to reactivate the entire lytic-replication cycle. ORF 50a functions as a sequence-specific transactivator that is capable of activating delayed-early gene expression via direct binding to an ORF 50 response element (RE) within the respective promoter. Here, it is shown that ORF 50a is capable of transactivating its own promoter. Deletion analysis of the ORF 50a promoter showed that the ORF 50-responsive element is contained within an 80 bp fragment, situated 293–373 bp from the transcription initiation site. Gel-retardation analysis further mapped the RE to a 34 bp fragment that was able to confer ORF 50 responsiveness to an enhancerless SV40 minimal promoter. Sequence analysis showed that this RE has no direct similarity to previously identified ORF 50 REs. Therefore, it is concluded that ORF 50a is capable of stimulating its own promoter via a novel RE.

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2005-03-01
2025-05-01
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References

  1. Albrecht J.-C., Nicholas J., Biller D. 8 other authors 1992; Primary structure of the herpesvirus saimiri genome. J Virol 66:5047–5058
     [Google Scholar]
  2. Brown H. J., Song M. J., Deng H., Wu T.-T., Cheng G., Sun R. 2003; NF- κ B inhibits gammaherpesvirus lytic replication. J Virol 77:8532–8540 [CrossRef]
     [Google Scholar]
  3. Chang L.-K., Liu S.-T. 2000; Activation of the BRLF1 promoter and lytic cycle of Epstein–Barr virus by histone acetylation. Nucleic Acids Res 28:3918–3925 [CrossRef]
     [Google Scholar]
  4. Chen J., Ueda K., Sakakibara S., Okuno T., Parravicini C., Corbellino M., Yamanishi K. 2001; Activation of latent Kaposi's sarcoma-associated herpesvirus by demethylation of the promoter of the lytic transactivator. Proc Natl Acad Sci U S A 98:4119–4124 [CrossRef]
     [Google Scholar]
  5. Damania B., Jeong J. H., Bowser B. S., DeWire S. M., Staudt M. R., Dittmer D. P. 2004; Comparison of the Rta/Orf50 transactivator proteins of gamma-2-herpesviruses. J Virol 78:5491–5499 [CrossRef]
     [Google Scholar]
  6. Deng H., Young A., Sun R. 2000; Auto-activation of the rta gene of human herpesvirus-8/Kaposi's sarcoma-associated herpesvirus. J Gen Virol 81:3043–3048
     [Google Scholar]
  7. Glaser G., Vogel M., Wolf H., Niller H. H. 1998; Regulation of the Epstein-Barr viral immediate early BRLF1 promoter through a distal NF1 site. Arch Virol 143:1967–1983 [CrossRef]
     [Google Scholar]
  8. Goodwin D. J., Hall K. T., Stevenson A. J., Markham A. F., Whitehouse A. 1999; The open reading frame 57 gene product of herpesvirus saimiri shuttles between the nucleus and cytoplasm and is involved in viral RNA nuclear export. J Virol 73:10519–10524
     [Google Scholar]
  9. Goodwin D. J., Walters M. S., Smith P. G., Thurau M., Fickenscher H., Whitehouse A. 2001; Herpesvirus saimiri open reading frame 50 (Rta) protein reactivates the lytic replication cycle in a persistently infected A549 cell line. J Virol 75:4008–4013 [CrossRef]
     [Google Scholar]
  10. Gorman C. M., Moffat L. F., Howard B. H. 1982; Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol 2:1044–1051
     [Google Scholar]
  11. Gruffat H., Sergeant A. 1994; Characterization of the DNA-binding site repertoire for the Epstein–Barr virus transcription factor R. Nucleic Acids Res 22:1172–1178 [CrossRef]
     [Google Scholar]
  12. Gruffat H., Manet E., Rigolet A., Sergeant A. 1990; The enhancer factor R of Epstein-Barr virus (EBV) is a sequence-specific DNA binding protein. Nucleic Acids Res 18:6835–6843 [CrossRef]
     [Google Scholar]
  13. Gruffat H., Duran N., Buisson M., Wild F., Buckland R., Sergeant A. 1992; Characterization of an R-binding site mediating the R-induced activation of the Epstein-Barr virus BMLF1 promoter. J Virol 66:46–52
     [Google Scholar]
  14. Hall K. T., Stevenson A. J., Goodwin D. J., Gibson P. C., Markham A. F., Whitehouse A. 1999; The activation domain of herpesvirus saimiri R protein interacts with the TATA-binding protein. J Virol 73:9756–9763
     [Google Scholar]
  15. Haque M., Davis D. A., Wang V., Widmer I., Yarchoan R. 2003; Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) contains hypoxia response elements: relevance to lytic induction by hypoxia. J Virol 77:6761–6768 [CrossRef]
     [Google Scholar]
  16. Himes S. R., Reeves R., Attema J., Nissen M., Li Y., Shannon M. F. 2000; The role of high-mobility group I(Y) proteins in expression of IL-2 and T cell proliferation. J Immunol 164:3157–3168 [CrossRef]
     [Google Scholar]
  17. Liang Y., Ganem D. 2003; Lytic but not latent infection by Kaposi's sarcoma-associated herpesvirus requires host CSL protein, the mediator of Notch signalling. Proc Natl Acad Sci U S A 100:8490–8495 [CrossRef]
     [Google Scholar]
  18. 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]
  19. Lukac D. M., 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. J Virol 73:9348–9361
     [Google Scholar]
  20. 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]
  21. 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 herpesvirus saimiri and the BMLF1-encoded transcriptional effector (EB2) of Epstein-Barr virus. J Virol 62:3250–3257
     [Google Scholar]
  22. 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 trans activator. J Virol 65:2457–2466
     [Google Scholar]
  23. Ragoczy T., Miller G. 1999; Role of the Epstein-Barr virus Rta protein in activation of distinct classes of viral lytic cycle genes. J Virol 73:9858–9866
     [Google Scholar]
  24. Ragoczy T., Miller G. 2001; Autostimulation of the Epstein-Barr virus BRLF1 promoter is mediated through consensus Sp1 and Sp3 binding sites. J Virol 75:5240–5251 [CrossRef]
     [Google Scholar]
  25. Ragoczy T., Heston L., Miller G. 1998; The Epstein-Barr virus Rta protein activates lytic cycle genes and can disrupt latency in B lymphocytes. J Virol 72:7978–7984
     [Google Scholar]
  26. Reeves R., Nissen M. S. 1990; The A·T-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA structure. J Biol Chem 265:8573–8582
     [Google Scholar]
  27. Reeves R., Nissen M. S. 1999; Purification and assays for high mobility group HMG-I(Y) protein function. Methods Enzymol 304:155–188
     [Google Scholar]
  28. 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]
  29. Sakakibara S., Ueda K., Chen J., Okuno T., Yamanishi K. 2001; Octamer-binding sequence is a key element for the autoregulation of Kaposi's sarcoma-associated herpesvirus ORF50/Lyta gene expression. J Virol 75:6894–6900 [CrossRef]
     [Google Scholar]
  30. 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]
  31. Virgin H. W. IV, 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. J Virol 71:5894–5904
     [Google Scholar]
  32. Walters M. S., Hall K. T., Whitehouse A. 2004; The herpesvirus saimiri open reading frame (ORF) 50 (Rta) protein contains an AT hook required for binding to the ORF 50 response element in delayed-early promoters. J Virol 78:4936–4942 [CrossRef]
     [Google Scholar]
  33. Wang S. E., Wu F. Y., Fujimuro M., Zong J., Hayward S. D., Hayward G. S. 2003; Role of CCAAT/enhancer-binding protein alpha (C/EBP α ) in activation of the Kaposi's sarcoma-associated herpesvirus (KSHV) lytic-cycle replication-associated protein (RAP) promoter in cooperation with the KSHV replication and transcription activator (RTA) and RAP. J Virol 77:600–623 [CrossRef]
     [Google Scholar]
  34. Whitehouse A., Carr I. M., Griffiths J. C., Meredith D. M. 1997a; The herpesvirus saimiri ORF50 gene, encoding a transcriptional activator homologous to the Epstein-Barr virus R protein, is transcribed from two distinct promoters of different temporal phases. J Virol 71:2550–2554
     [Google Scholar]
  35. Whitehouse A., Stevenson A. J., Cooper M., Meredith D. M. 1997b; Identification of a cis -acting element within the herpesvirus saimiri ORF 6 promoter that is responsive to the HVS.R transactivator. J Gen Virol 78:1411–1415
     [Google Scholar]
  36. 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. J Virol 72:1967–1973
     [Google Scholar]
  37. 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. J Virol 72:857–861
     [Google Scholar]
  38. Wu T.-T., Usherwood E. J., Stewart J. P., Nash A. A., Sun R. 2000; Rta of murine gammaherpesvirus 68 reactivates the complete lytic cycle from latency. J Virol 74:3659–3667 [CrossRef]
     [Google Scholar]
  39. Zalani S., Holley-Guthrie E. A., Gutsch D. E., Kenney S. C. 1992; The Epstein-Barr virus immediate-early promoter BRLF1 can be activated by the cellular Sp1 transcription factor. J Virol 66:7282–7289
     [Google Scholar]
  40. Zalani S., Holley-Guthrie E., Kenney S. 1995; The Zif268 cellular transcription factor activates expression of the Epstein-Barr virus immediate-early BRLF1 promoter. J Virol 69:3816–3823
     [Google Scholar]
  41. 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. Proc Natl Acad Sci U S A 93:9194–9199 [CrossRef]
     [Google Scholar]
  42. Zalani S., Coppage A., Holley-Guthrie E., Kenney S. 1997; The cellular YY1 transcription factor binds a cis -acting, negatively regulating element in the Epstein-Barr virus BRLF1 promoter. J Virol 71:3268–3274
     [Google Scholar]
/content/journal/jgv/10.1099/vir.0.80723-0
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The herpesvirus saimiri Rta gene autostimulates via binding to a non-consensus response element
J. Gen. Virol. 86, 581 (2005); https://doi.org/10.1099/vir.0.80723-0
/content/journal/jgv/10.1099/vir.0.80723-0
/content/journal/jgv/10.1099/vir.0.80723-0
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