1887

Abstract

Herpesvirus saimiri (HVS) establishes a latent infection in which the viral genome persists as a non-integrated episome. Analysis has shown that only open reading frames (ORFs) 71–73 are transcribed in an model of HVS latency. ORF73 also colocalizes with HVS genomic DNA on host mitotic chromosomes and maintains the stability of HVS terminal-repeat-containing plasmids. However, it is not known whether ORF73 is the only HVS-encoded protein required for episomal maintenance. In this study, the elements required for episomal maintenance in the context of a full-length HVS genome were examined by mutational analysis. A recombinant virus, HVS-BACΔ71-73, lacking the latency-associated genes was unable to persist in a dividing cell population. However, retrofitting an ORF73 expression cassette into the recombinant virus rescued episomal maintenance. This indicates that ORF73 is the key -acting factor for episomal persistence and efficient establishment of a latent infection.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81230-0
2005-10-01
2019-10-22
Loading full text...

Full text loading...

/deliver/fulltext/jgv/86/10/2703.html?itemId=/content/journal/jgv/10.1099/vir.0.81230-0&mimeType=html&fmt=ahah

References

  1. Albrecht, J., Nicholas, J., Biller, D. & 7 other authors ( 1992; ). Primary structure of the herpesvirus saimiri genome. J Virol 66, 5047–5058.
    [Google Scholar]
  2. 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]
  3. Calderwood, M. A., Hall, K. T., Matthews, D. A. & Whitehouse, A. ( 2004; ). The herpesvirus saimiri ORF73 gene product interacts with host-cell mitotic chromosomes and self-associates via its C terminus. J Gen Virol 85, 147–153.[CrossRef]
    [Google Scholar]
  4. Chang, Y., Moore, P. S., Talbot, S. J., Boshoff, C. H., Zarkowska, T., Godden, K., Paterson, H., Weiss, R. A. & Mittnacht, S. ( 1996; ). Cyclin encoded by KS herpesvirus. Nature 382, 410.[CrossRef]
    [Google Scholar]
  5. Collins, C. M. & Medveczky, P. G. ( 2002; ). Genetic requirements for the episomal maintenance of oncogenic herpesvirus genomes. Adv Cancer Res 84, 155–174.
    [Google Scholar]
  6. Collins, C. M., Medveczky, M. M., Lund, T. & Medveczky, P. G. ( 2002; ). The terminal repeats and latency-associated nuclear antigen of herpesvirus saimiri are essential for episomal persistence of the viral genome. J Gen Virol 83, 2269–2278.
    [Google Scholar]
  7. Cotter, M. A. & 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]
  8. Dittmer, D., Lagunoff, M., Renne, R., Staskus, K., Haase, A. & Ganem, D. ( 1998; ). A cluster of latently expressed genes in Kaposi's sarcoma-associated herpesvirus. J Virol 72, 8309–8315.
    [Google Scholar]
  9. Fickenscher, H. & Fleckenstein, B. ( 2001; ). Herpesvirus saimiri. Philos Trans R Soc Lond B Biol Sci 356, 545–567.[CrossRef]
    [Google Scholar]
  10. Hall, K. T., Giles, M. S., Goodwin, D. J., Calderwood, M. A., Carr, I. M., Stevenson, A. J., Markham, A. F. & Whitehouse, A. ( 2000a; ). Analysis of gene expression in a human cell line stably transduced with herpesvirus saimiri. J Virol 74, 7331–7337.[CrossRef]
    [Google Scholar]
  11. Hall, K. T., Giles, M. S., Goodwin, D. J., Calderwood, M. A., Markham, A. F. & Whitehouse, A. ( 2000b; ). Characterization of the herpesvirus saimiri ORF73 gene product. J Gen Virol 81, 2653–2658.
    [Google Scholar]
  12. Hu, J., Garber, A. C. & Renne, R. ( 2002; ). The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus supports latent DNA replication in dividing cells. J Virol 76, 11677–11687.[CrossRef]
    [Google Scholar]
  13. Jung, J. U., Stager, M. & Desrosiers, R. C. ( 1994; ). Virus-encoded cyclin. Mol Cell Biol 14, 7235–7244.
    [Google Scholar]
  14. Kapoor, P. & Frappier, L. ( 2003; ). EBNA1 partitions Epstein–Barr virus plasmids in yeast cells by attaching to human EBNA1-binding protein 2 on mitotic chromosomes. J Virol 77, 6946–6956.[CrossRef]
    [Google Scholar]
  15. Kapoor, P., Shire, K. & Frappier, L. ( 2001; ). Reconstitution of Epstein–Barr virus-based plasmid partitioning in budding yeast. EMBO J 20, 222–230.[CrossRef]
    [Google Scholar]
  16. 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. J Clin Invest 100, 2606–2610.[CrossRef]
    [Google Scholar]
  17. 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. J Hum Virol 1, 19–29.
    [Google Scholar]
  18. Krithivas, A., Fujimuro, M., Weidner, M., Young, D. B. & Hayward, S. D. ( 2002; ). Protein interactions targeting the latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus to cell chromosomes. J Virol 76, 11596–11604.[CrossRef]
    [Google Scholar]
  19. Lalioti, M. & Heath, J. ( 2001; ). A new method for generating point mutations in bacterial artificial chromosomes by homologous recombination in Escherichia coli. Nucleic Acids Res 29, E14.[CrossRef]
    [Google Scholar]
  20. Lee, M.-A., Diamond, M. E. & Yates, J. L. ( 1999; ). Genetic evidence that EBNA-1 is needed for efficient, stable latent infection by Epstein–Barr virus. J Virol 73, 2974–2982.
    [Google Scholar]
  21. Leight, E. R. & Sugden, B. ( 2000; ). EBNA-1: a protein pivotal to latent infection by Epstein–Barr virus. Rev Med Virol 10, 83–100.[CrossRef]
    [Google Scholar]
  22. Lupton, S. & Levine, A. J. ( 1985; ). Mapping genetic elements of Epstein–Barr virus that facilitate extrachromosomal persistence of Epstein–Barr virus-derived plasmids in human cells. Mol Cell Biol 5, 2533–2542.
    [Google Scholar]
  23. Piolot, T., Tramier, M., Coppey, M., Nicolas, J.-C. & Marechal, V. ( 2001; ). Close but distinct regions of human herpesvirus 8 latency-associated nuclear antigen 1 are responsible for nuclear targeting and binding to human mitotic chromosomes. J Virol 75, 3948–3959.[CrossRef]
    [Google Scholar]
  24. Rainbow, L., Platt, G., Simpson, G., Sarid, R., Gao, S., Stoiber, H., Herrington, C., Moore, P. & Schulz, T. ( 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. J Virol 71, 5915–5921.
    [Google Scholar]
  25. 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]
  26. Shinohara, H., Fukushi, M., Higuchi, M., Oie, M., Hoshi, O., Ushiki, T., Hayashi, J.-I. & Fujii, M. ( 2002; ). Chromosome binding site of latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus is essential for persistent episome maintenance and is functionally replaced by histone H1. J Virol 76, 12917–12924.[CrossRef]
    [Google Scholar]
  27. Shire, K., Ceccarelli, D. F. J., Avolio-Hunter, T. M. & Frappier, L. ( 1999; ). EBP2, a human protein that interacts with sequences of the Epstein–Barr virus nuclear antigen 1 important for plasmid maintenance. J Virol 73, 2587–2595.
    [Google Scholar]
  28. Smith, P. G., Coletta, P. L., Markham, A. F. & Whitehouse, A. ( 2001; ). In vivo episomal maintenance of a herpesvirus saimiri-based gene delivery vector. Gene Ther 8, 1762–1769.[CrossRef]
    [Google Scholar]
  29. Talbot, S. J., Weiss, R. A., Kellam, P. & Boshoff, C. ( 1999; ). Transcriptional analysis of human herpesvirus-8 open reading frames 71, 72, 73, K14, and 74 in a primary effusion lymphoma cell line. Virology 257, 84–94.[CrossRef]
    [Google Scholar]
  30. Thome, M., Schneider, P., Hofmann, K. & 11 other authors ( 1997; ). Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors. Nature 386, 517–521.[CrossRef]
    [Google Scholar]
  31. Verma, S. C. & Robertson, E. S. ( 2003; ). ORF73 of herpesvirus saimiri strain C488 tethers the viral genome to metaphase chromosomes and binds to cis-acting DNA sequences in the terminal repeats. J Virol 77, 12494–12506.[CrossRef]
    [Google Scholar]
  32. Virgin, H., IV, Latreille, P., Wamsley, P., Hallsworth, K., Weck, K., Dal Canto, A. & Speck, S. ( 1997; ). Complete sequence and genomic analysis of murine gammaherpesvirus 68. J Virol 71, 5894–5904.
    [Google Scholar]
  33. White, R. E., Calderwood, M. A. & Whitehouse, A. ( 2003; ). Generation and precise modification of a herpesvirus saimiri bacterial artificial chromosome demonstrates that the terminal repeats are required for both virus production and episomal persistence. J Gen Virol 84, 3393–3403.[CrossRef]
    [Google Scholar]
  34. Wu, H., Kapoor, P. & Frappier, L. ( 2002; ). Separation of the DNA replication, segregation, and transcriptional activation functions of Epstein–Barr nuclear antigen 1. J Virol 76, 2480–2490.[CrossRef]
    [Google Scholar]
  35. Yates, J., Warren, N., Reisman, D. & Sugden, B. ( 1984; ). A cis-acting element from the Epstein–Barr viral genome that permits stable replication of recombinant plasmids in latently infected cells. Proc Natl Acad Sci U S A 81, 3806–3810.[CrossRef]
    [Google Scholar]
  36. Yates, J. L., Warren, N. & Sugden, B. ( 1985; ). Stable replication of plasmids derived from Epstein–Barr virus in various mammalian cells. Nature 313, 812–815.[CrossRef]
    [Google Scholar]
  37. Ye, F. C., Zhou, F. C., Yoo, S. M., Xie, J. P., Browning, P. J. & Gao, S. J. ( 2004; ). Disruption of Kaposi's sarcoma-associated herpesvirus latent nuclear antigen leads to abortive episome persistence. J Virol 78, 11121–11129.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81230-0
Loading
/content/journal/jgv/10.1099/vir.0.81230-0
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