1887

Abstract

LANA, the major latency-associated nuclear antigen of Kaposi’s sarcoma herpesvirus/human herpesvirus-8 (KSHV/HHV-8), binds RING3 protein, one of five human homologues of the (female sterile homeotic) gene product of . In KSHV/HHV-8-infected cells LANA and the viral episomes accumulate in heterochromatin-associated nuclear bodies. Here we show that in several KSHV/HHV-8-negative cell lines derived from carcinomas, sarcomas and lymphomas, RING3 was expressed at low levels, primarily localized to the euchromatin, and dissociated from the chromosomes during mitosis. In contrast, in KSHV/HHV-8-infected body cavity lymphoma cells the bulk of RING3 localizes to the LANA nuclear bodies and remains associated with the chromosomes during cell division. KSHV/HHV-8-infected body cavity lymphoma cells expressed RING3 at much higher levels than cells without the virus. Transfection of full-length LANA, but not the C terminus alone, greatly induced RING3 gene expression, and LANA and RING3 co-localized even in the transfected cells, in the absence of KSHV/HHV-8 viral DNA. High levels of LANA expression led to the disappearance of heterochromatin in both human and mouse cells. We suggest that LANA and RING3 may create a local euchromatic microenvironment around the viral episomes that are anchored to the heterochromatin.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-83-1-179
2002-01-01
2019-10-14
Loading full text...

Full text loading...

/deliver/fulltext/jgv/83/1/0830179a.html?itemId=/content/journal/jgv/10.1099/0022-1317-83-1-179&mimeType=html&fmt=ahah

References

  1. Ballestas, M. E., Chatis, P. A. & Kaye, K. M. ( 1999; ). Efficient persistence of extrachromosomal KSHV DNA mediated by latency-associated nuclear antigen. Science 284, 641-644.[CrossRef]
    [Google Scholar]
  2. Beck, S., Hanson, I., Kelly, A., Pappin, D. J. & Trowsdale, J. ( 1992; ). A homologue of the Drosophila female sterile homeotic (fsh) gene in the class II region of the human MHC. DNA Sequence 2, 203-210.
    [Google Scholar]
  3. Beck, S., Belich, M., Gruneberg, U., Jackson, A., Kelly, A., Sanseau, P., Sanderson, F., Trowsdale, J. & Van Ham, M. ( 1996; ). Organisation and functions of class II genes and molecules. DNA Sequence 7, 21-23.
    [Google Scholar]
  4. Boshoff, C. & Weiss, R. A. ( 1998; ). Kaposi’s sarcoma-associated herpesvirus. Advances in Cancer Research 75, 57-86.
    [Google Scholar]
  5. Cotter, M. A.II & Robertson, E. S. ( 1999; ). The latency-associated nuclear antigen tethers the Kaposi’s sarcoma-associated herpesvirus genome to host chromosomes in body cavity-based lymphoma cells. Virology 264, 254-264.[CrossRef]
    [Google Scholar]
  6. Dey, A., Ellenberg, J., Farina, A., Coleman, A. E., Maruyama, T., Sciortino, S., Lippincott-Schwartz, J. & Ozato, K. ( 2000; ). A bromodomain protein, MCAP, associates with mitotic chromosomes and affects G2-to-M transition. Molecular and Cellular Biology 20, 6537-6549.[CrossRef]
    [Google Scholar]
  7. Dhalluin, C., Carlson, J. E., Zeng, L., He, C., Aggarwal, A. K. & Zhou, M. M. ( 1999; ). Structure and ligand of a histone acetyltransferase bromodomain. Nature 399, 491-496.[CrossRef]
    [Google Scholar]
  8. Dupin, N., Fisher, C., Kellam, P., Ariad, S., Tulliez, M., Franck, N., van Marck, E., Salmon, D., Gorin, I., Escande, J. P., Weiss, R. A., Alitalo, K. & Boshoff, C. ( 1999; ). Distribution of human herpesvirus-8 latently infected cells in Kaposi’s sarcoma, multicentric Castleman’s disease, and primary effusion lymphoma. Proceedings of the National Academy of Sciences, USA 96, 4546-4551.[CrossRef]
    [Google Scholar]
  9. Finke, J., Rowe, M., Kallin, B., Ernberg, I., Rosen, A., Dillner, J. & Klein, G. ( 1987; ). Monoclonal and polyclonal antibodies against Epstein–Barr virus nuclear antigen 5 (EBNA-5) detect multiple protein species in Burkitt’s lymphoma and lymphoblastoid cell lines. Journal of Virology 61, 3870-3878.
    [Google Scholar]
  10. Friborg, J.Jr, Kong, W., Hottiger, M. O. & Nabel, G. J. ( 1999; ). p53 inhibition by the LANA protein of KSHV protects against cell death. Nature 402, 889-894.
    [Google Scholar]
  11. Holmvall, P. & Szekely, L. ( 1999; ). Computer programs that allow fast acquisition, visualization and overlap quantitation of fluorescent 3D microscopic objects using nearest neighbor deconvolution algorithm. Applied Immunohistochemistry & Molecular Morphology 7, 226-236.
    [Google Scholar]
  12. Jones, M. H., Numata, M. & Shimane, M. ( 1997; ). Identification and characterization of BRDT: a testis-specific gene related to the bromodomain genes RING3 and Drosophila fsh. Genomics 45, 529-534.[CrossRef]
    [Google Scholar]
  13. Katano, H., Sato, Y., Kurata, T., Mori, S. & Sata, T. ( 1999; ). High expression of HHV-8-encoded ORF73 protein in spindle-shaped cells of Kaposi’s sarcoma. American Journal of Pathology 155, 47-52.[CrossRef]
    [Google Scholar]
  14. Kedes, D. H., Lagunoff, M., Renne, R. & Ganem, D. ( 1997; ). Identification of the gene encoding the major latency-associated nuclear antigen of the Kaposi’s sarcoma-associated herpesvirus. Journal of Clinical Investigation 100, 2606-2610.[CrossRef]
    [Google Scholar]
  15. Kellam, P., Boshoff, C., Whitby, D., Matthews, S., Weiss, R. A. & Talbot, S. J. ( 1997; ). Identification of a major latent nuclear antigen, LNA-1, in the human herpesvirus 8 genome. Journal of Human Virology 1, 19-29.
    [Google Scholar]
  16. Krithivas, A., Young, D. B., Liao, G., Greene, D. & Hayward, S. D. ( 2000; ). Human herpesvirus 8 LANA interacts with proteins of the mSin3 corepressor complex and negatively regulates Epstein–Barr virus gene expression in dually infected PEL cells. Journal of Virology 74, 9637-9645.[CrossRef]
    [Google Scholar]
  17. Lau, A. O. T., Sacci, J. B. & Azad, A. F. ( 2001; ). Host responses to Plasmodium yoelii hepatic stages: a paradigm in host–parasite interaction. Journal of Immunology 166, 1945-1950.[CrossRef]
    [Google Scholar]
  18. Mozer, B. A. & Dawid, I. B. ( 1989; ). Cloning and molecular characterization of the trithorax locus of Drosophila melanogaster. Proceedings of the National Academy of Sciences, USA 86, 3738-3742.[CrossRef]
    [Google Scholar]
  19. Platt, G. M., Simpson, G. R., Mittnacht, S. & Schulz, T. F. ( 1999; ). Latent nuclear antigen of Kaposi’s sarcoma-associated herpesvirus interacts with RING3, a homolog of the Drosophila female sterile homeotic (fsh) gene. Journal of Virology 73, 9789-9795.
    [Google Scholar]
  20. Pokrovskaja, K., Mattsson, K., Kashuba, E., Klein, G. & Szekely, L. ( 2001; ). Proteasome inhibitor induces nucleolar translocation of the EBV-encoded EBNA-5. Journal of General Virology 82, 345-358.
    [Google Scholar]
  21. Radkov, S. A., Kellam, P. & Boshoff, C. ( 2000; ). The latent nuclear antigen of Kaposi sarcoma-associated herpesvirus targets the retinoblastoma–E2F pathway and with the oncogene Hras transforms primary rat cells. Nature Medicine 6, 1121-1127.[CrossRef]
    [Google Scholar]
  22. Rainbow, L., Platt, G. M., Simpson, G. R., Sarid, R., Gao, S. J., Stoiber, H., Herrington, C. S., Moore, P. S. & Schulz, T. F. ( 1997; ). The 222- to 234-kilodalton latent nuclear protein (LNA) of Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) is encoded by orf73 and is a component of the latency-associated nuclear antigen. Journal of Virology 71, 5915-5921.
    [Google Scholar]
  23. Renne, R., Barry, C., Dittmer, D., Compitello, N., Brown, P. O. & Ganem, D. ( 2001; ). Modulation of the cellular and viral gene expression by the latency-associated nuclear antigen of Kaposi’s sarcoma-associated herpesvirus. Journal of Virology 75, 458-468.[CrossRef]
    [Google Scholar]
  24. Rhee, K., Brunori, M., Besset, V., Trousdale, R. & Wolgemuth, D. J. ( 1998; ). Expression and potential role of Fsrg1, a murine bromodomain-containing homologue of the Drosophila gene female sterile homeotic. Journal of Cell Science 111, 3541-3550.
    [Google Scholar]
  25. Szekely, L., Chen, F., Teramoto, N., Ehlin-Henriksson, B., Pokrovskaja, K., Szeles, A., Manneborg-Sandlund, A., Löwbeer, M., Lennette, E. T. & Klein, G. ( 1998; ). Restricted expression of Epstein–Barr virus (EBV)-encoded, growth transformation-associated antigens in an EBV- and human herpesvirus type 8-carrying body cavity lymphoma line. Journal of General Virology 79, 1445-1452.
    [Google Scholar]
  26. Szekely, L., Kiss, C., Mattsson, K., Kashuba, E., Pokrovskaja, K., Juhasz, A., Holmvall, P. & Klein, G. ( 1999; ). Human herpesvirus-8-encoded LNA-1 accumulates in heterochromatin-associated nuclear bodies. Journal of General Virology 80, 2889-2900.
    [Google Scholar]
  27. Taniguchi, Y., Matsuzaka, Y., Fujimoto, H., Miyado, K., Kohda, A., Okumura, K., Kimura, M. & Inoko, H. ( 1998; ). Nucleotide sequence of the ring3 gene in the class II region of the mouse MHC and its abundant expression in testicular germ cells. Genomics 51, 114-123.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-83-1-179
Loading
/content/journal/jgv/10.1099/0022-1317-83-1-179
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error