The human herpesvirus-8 ORF 57 gene and its properties Free

Abstract

Human herpesvirus-8 (HHV-8) is a γ lymphotropic herpesvirus associated with Kaposi’s sarcoma, a major neoplasm of AIDS patients, and with other AIDS-related neoplasms. The HHV-8 ORF 57 gene is conserved throughout the herpesvirus family and has a herpes simplex virus type 1 homologue, IE63 (also termed ICP27), which is an essential regulatory protein and acts at both transcriptional and post-transcriptional levels. We show that, contrary to the published HHV-8 sequence, which predicts a protein of 275 amino acids, the ORF 57 gene is spliced, contains a single intron and encodes a protein of 455 amino acids. For several gammaherpesviruses examined, the upstream coding exon is 16–17 amino acids in length and is rich in methionine residues. When ORF 57 was fused to the gene for enhanced green fluorescent protein (EGFP), the fusion protein exhibited a punctate nuclear distribution that co-localized with the cellular splicing factor SC-35. Unlike the IE63–EGFP fusion protein, ORF 57–EGFP did not shuttle from the nucleus to the cytoplasm in the presence of actinomycin D. However, ORF 57–EGFP was capable of shuttling from a transfected monkey nucleus to a recipient mouse nucleus in an interspecies heterokaryon assay. These data indicate that HHV-8 ORF 57 and IE63 possess certain common properties.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-80-12-3207
1999-12-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/80/12/0803207.html?itemId=/content/journal/jgv/10.1099/0022-1317-80-12-3207&mimeType=html&fmt=ahah

References

  1. Albrecht J.-C., Nicholas J., Biller D., Cameron K. R., Biesinger B., Newman C., Wittmann 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. Arvanitakis L., Mesri E. A., Nador R. G., Said J. W., Asch A. S., Knowles D. M., Cesarman E. 1996; Establishment and characterization of a primary effusion (body cavity-based) lymphoma cell line (BC-3) harboring Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8) in the absence of Epstein–Barr virus. Blood 88:2648–2654
    [Google Scholar]
  3. Baer R., Bankier A. T., Biggin M. D., Deininger P. L., Farrell P. J., Gibson T. J., Hatfull G., Hudson G. S., Satchwell S. C., Seguin C., Tuffnell P. S., Barrell B. G. 1984; DNA sequence and expression of the B95-8 Epstein–Barr virus genome. Nature 310:207–211
    [Google Scholar]
  4. Boshoff C., Gao S. J., Healy L. E., Matthews S., Thomas A. J., Coignet L., Warnke R. A., Strauchen J. A., Matutes E., Kamel O. W., Moore P. S., Weiss R. A., Chang Y. 1998; Establishing a KSHV+ cell line (BCP-1) from peripheral blood and characterizing its growth in Nod/SCID mice. Blood 91:1671–1679
    [Google Scholar]
  5. Brown T., Mackey K. 1997; Analysis of RNA by Northern and slot blot hybridization. Current Protocols in Molecular Biology4.9.1–4.9.16
    [Google Scholar]
  6. 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]
  7. Buisson M., Hans F., Kusters I., Duran N., Sergeant A. 1999; The C-terminal region but not the Arg-X-Pro repeat of Epstein–Barr virus protein EB2 is required for its effect on RNA splicing and transport. Journal of Virology 73:4090–4100
    [Google Scholar]
  8. 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
    [Google Scholar]
  9. 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
    [Google Scholar]
  10. 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]
  11. Defechereux P., Debrus S., Baudoux L., Rentier B., Piette J. 1997; Varicella-zoster virus open reading frame 4 encodes an immediate-early protein with posttranscriptional regulatory properties. Journal of Virology 71:7073–7079
    [Google Scholar]
  12. Ensser A., Pflanz R., Fleckenstein B. 1997; Primary structure of the alcelaphine herpesvirus 1 genome. Journal of Virology 71:6517–6525
    [Google Scholar]
  13. Gao S. J., Kingsley L., Li M., Zheng W., Parravicini C., Ziegler J., Newton R., Rinaldo C. R., Saah A., Phair J., Detels R., Chang Y., Moore P. S. 1996; KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi’s sarcoma. Nature Medicine 2:925–928
    [Google Scholar]
  14. Hagting A., Karlsson C., Clute P., Jackman M., Pines J. 1998; MPF localization is controlled by nuclear export. EMBO Journal 17:4127–4138
    [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
    [Google Scholar]
  16. McGeoch D. J., Cook S., Dolan A., Jamieson F. E., Telford E. A. R. 1995; Molecular phylogeny and evolutionary timescale for the family of mammalian herpesviruses. Journal of Molecular Biology 247:443–458
    [Google Scholar]
  17. Mackett M., Stewart J. P., Pepper S. de V., Chee M., Efstathiou S., Nash A. A., Arrand J. R. 1997; Genetic content and preliminary transcriptional analysis of a representative region of murine gammaherpesvirus 68. Journal of General Virology 78:1425–1433
    [Google Scholar]
  18. Mears W. E., Rice S. A. 1998; The herpes simplex virus immediate-early protein ICP27 shuttles between nucleus and cytoplasm. Virology 242:128–137
    [Google Scholar]
  19. Moore P. S., Gao S. J., Dominguez G., Cesarman E., Lungu O., Knowles D. M., Garber R., Pellett P. E., McGeoch D. J., Chang Y. 1996; Primary characterization of a herpesvirus agent associated with Kaposi’s sarcomae. Journal of Virology 70:549–558
    [Google Scholar]
  20. Nador R. G., Cesarman E., Knowles D. M., Said J. W. 1995; Herpes-like DNA sequences in body-cavity-based lymphoma in an HIV-negative patient. New England Journal of Medicine 333:943
    [Google Scholar]
  21. Phelan A., Clements J. B. 1997; Herpes simplex virus type 1 immediate early protein IE63 shuttles between nuclear compartments and the cytoplasm. Journal of General Virology 78:3327–3331
    [Google Scholar]
  22. Phelan A., Clements J. B. 1998; Posttranscriptional regulation in herpes simplex virus. Seminars in Virology 8:309–318
    [Google Scholar]
  23. Phelan A., Carmo-Fonseca M., McLaughlan J., Lamond A. I., Clements J. B. 1993; A herpes simplex virus type 1 immediate-early gene product, IE63, regulates small nuclear ribonucleoprotein distribution. Proceedings of the National Academy of Sciences, USA 90:9056–9060
    [Google Scholar]
  24. Pinol-Roma S., Dreyfuss G. 1992; Shuttling of pre-mRNA binding proteins between nucleus and cytoplasm. Nature 355:730–732
    [Google Scholar]
  25. 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
    [Google Scholar]
  26. Russo J. J., Bohenzky R. A., Chien M.-C., Chen J., Yan M., Maddalena D., Parry J. P., Peruzzi D., Edelman I. S., Chang Y., Moore P. S. 1996; Nucleotide sequence of the Kaposi’s sarcoma-associated herpesvirus (HHV8). Proceedings of the National Academy of Sciences USA 93:14862–14867
    [Google Scholar]
  27. Sample J., Lancz G., Nonoyama M. 1986; Mapping of genes in Bam HI fragment M of Epstein–Barr virus DNA that may determine the fate of viral infection. Journal of Virology 57:145–154
    [Google Scholar]
  28. Sandri-Goldin R. M. 1998a; ICP27 mediates HSV RNA export by shuttling through a leucine-rich nuclear export signal and binding viral intronless RNAs through an RGG motif. Genes & Development 12:868–879
    [Google Scholar]
  29. Sandri-Goldin R. M. 1998b; Interactions between a herpes simplex virus regulatory protein and cellular mRNA processing pathways. Methods 16:95–104
    [Google Scholar]
  30. Sarid R., Flore O., Bohenzky R. A., Chang Y., Moore P. S. 1998; Transcription mapping of the Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) genome in a body cavity-based lymphoma cell line (BC-1). Journal of Virology 72:1005–1012
    [Google Scholar]
  31. Schulz T. F. 1998; Kaposi’s sarcoma-associated herpesvirus (human herpesvirus-8). Journal of General Virology 79:1573–1591
    [Google Scholar]
  32. Searles R. P., Bergquam E. P., Axthelm M. K., Wong S. W. 1999; Sequence and genomic analysis of a rhesus macaque rhadinovirus with similarity to Kaposi’s sarcoma-associated herpesvirus/human herpesvirus 8. Journal of Virology 73:3040–3053
    [Google Scholar]
  33. Simpson G. R., Schulz T. F., Whitby D., Cook P. M., Boshoff C., Rainbow L., Howard M. R., Gao S. J., Bohenzky R. A., Simmonds P., Lee C., de Ruiter A., Hatzakis A., Tedder R. S., Weller I. V., Weiss R. A., Moore P. S. 1996; Prevalence of Kaposi’s sarcoma associated herpesvirus infection measured by antibodies to recombinant capsid protein and latent immunofluorescence antigen. Lancet 348:1133–1138
    [Google Scholar]
  34. Soulier J., Grollet L., Oksenhendler E., Cacoub P., Cazals-Hatem D., Babinet P., d’Agay M. F., Clauvel J. P., Raphael M., Degos L. 1995; Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman’s disease. Blood 86:1276–1280
    [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 Kaposi’s sarcoma-associated herpesvirus. Proceedings of the National Academy of Sciences, USA 95:10866–10871
    [Google Scholar]
  36. Sun R., Lin S. F., Staskus K., Gradoville L., Grogan E., Haase A., Miller G. 1999; Kinetics of Kaposi’s sarcoma-associated herpesvirus gene expression. Journal of Virology 73:2232–2242
    [Google Scholar]
  37. Sunil-Chandra N. P., Efstathiou S., Arno J., Nash A. A. 1992; Virological and pathological features of mice infected with murine gammaherpesvirus 68. Journal of General Virology 73:2347–2356
    [Google Scholar]
  38. Telford E. A. R., Watson M. S., Aird H., Perry J., Davison A. J. 1995; The DNA sequence of equine herpesvirus 2. Journal of Molecular Biology 249:520–528
    [Google Scholar]
  39. 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
    [Google Scholar]
  40. Whitehouse A., Cooper M., Meredith D. M. 1998a; 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]
  41. Whitehouse A., Cooper M., Hall K. T., Meredith D. M. 1998b; 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. 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 transactivator of gene expression. Journal of Virology 68:3943–3954
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-80-12-3207
Loading
/content/journal/jgv/10.1099/0022-1317-80-12-3207
Loading

Data & Media loading...

Most cited Most Cited RSS feed