1887

Abstract

is widely conserved among herpesviruses but its function during infection is poorly understood. Previously, we discovered a genetic link between and the herpes simplex virus 1-induced dispersal of the nucleolar protein nucleolin. Here, we report that in the absence of viral infection, transiently expressed UL24 accumulated in both the nucleus and the Golgi apparatus. In the majority of transfected cells, nuclear staining for UL24 was diffuse, but a minor staining pattern, whereby UL24 was present in nuclear foci corresponding to nucleoli, was also observed. Expression of UL24 correlated with the dispersal of nucleolin. This dispersal did not appear to be a consequence of a general disaggregation of nucleoli, as foci of fibrillarin staining persisted in cells expressing UL24. The conserved N-terminal region of UL24 was sufficient to cause this change in subcellular distribution of nucleolin. Interestingly, a bipartite nuclear localization signal predicted within the C terminus of UL24 was dispensable for nuclear localization. None of the five individual UL24 homology domains was required for nuclear or Golgi localization, but deletion of these domains resulted in the loss of nucleolin-dispersal activity. We determined that a nucleolar-targeting signal was contained within the first 60 aa of UL24. Our results show that the conserved N-terminal domain of UL24 is sufficient to specifically induce dispersal of nucleolin in the absence of other viral proteins or virus-induced cellular modifications. These results suggest that UL24 directly targets cellular factors that affect the composition of nucleoli.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.83573-0
2008-05-01
2019-11-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/89/5/1142.html?itemId=/content/journal/jgv/10.1099/vir.0.83573-0&mimeType=html&fmt=ahah

References

  1. Avitabile, E., Di Gaeta, S., Torrisi, M. R., Ward, P. L., Roizman, B. & Campadelli-Fiume, G. ( 1995; ). Redistribution of microtubules and Golgi apparatus in herpes simplex virus-infected cells and their role in viral exocytosis. J Virol 69, 7472–7482.
    [Google Scholar]
  2. Besse, S. & Puvion-Dutilleul, F. ( 1996; ). Intranuclear retention of ribosomal RNAs in response to herpes simplex virus type 1 infection. J Cell Sci 109, 119–129.
    [Google Scholar]
  3. Blakeney, S., Kowalski, J., Tummolo, D., DeStefano, J., Cooper, D., Guo, M., Gangolli, S., Long, D., Zamb, T. & other authors ( 2005; ). Herpes simplex virus type 2 UL24 gene is a virulence determinant in murine and guinea pig disease models. J Virol 79, 10498–10506.[CrossRef]
    [Google Scholar]
  4. Boisvert, F. M., van Koningsbruggen, S., Navascues, J. & Lamond, A. I. ( 2007; ). The multifunctional nucleolus. Nat Rev Mol Cell Biol 8, 574–585.
    [Google Scholar]
  5. Burch, A. D. & Weller, S. K. ( 2004; ). Nuclear sequestration of cellular chaperone and proteasomal machinery during herpes simplex virus type 1 infection. J Virol 78, 7175–7185.[CrossRef]
    [Google Scholar]
  6. Campadelli, G., Brandimarti, R., Di Lazzaro, C., Ward, P. L., Roizman, B. & Torrisi, M. R. ( 1993; ). Fragmentation and dispersal of Golgi proteins and redistribution of glycoproteins and glycolipids processed through the Golgi apparatus after infection with herpes simplex virus 1. Proc Natl Acad Sci U S A 90, 2798–2802.[CrossRef]
    [Google Scholar]
  7. De Brabander, M. J., Van de Veire, R. M., Aerts, F. E., Borgers, M. & Janssen, P. A. ( 1976; ). The effects of methyl (5-(2-thienylcarbonyl)-1H-benzimidazol-2-yl) carbamate, (R 17934; NSC 238159), a new synthetic antitumoral drug interfering with microtubules, on mammalian cells cultured in vitro. Cancer Res 36, 905–916.
    [Google Scholar]
  8. Everett, R. D., Earnshaw, W. C., Findlay, J. & Lomonte, P. ( 1999; ). Specific destruction of kinetochore protein CENP-C and disruption of cell division by herpes simplex virus immediate-early protein Vmw110. EMBO J 18, 1526–1538.[CrossRef]
    [Google Scholar]
  9. Griffiths, A. & Coen, D. M. ( 2003; ). High-frequency phenotypic reversion and pathogenicity of an acyclovir-resistant herpes simplex virus mutant. J Virol 77, 2282–2286.[CrossRef]
    [Google Scholar]
  10. Harley, C. A., Dasgupta, A. & Wilson, D. W. ( 2001; ). Characterization of herpes simplex virus-containing organelles by subcellular fractionation: role for organelle acidification in assembly of infectious particles. J Virol 75, 1236–1251.[CrossRef]
    [Google Scholar]
  11. Hong-Yan, Z., Murata, T., Goshima, F., Takakuwa, H., Koshizuka, T., Yamauchi, Y. & Nishiyama, Y. ( 2001; ). Identification and characterization of the UL24 gene product of herpes simplex virus type 2. Virus Genes 22, 321–327.[CrossRef]
    [Google Scholar]
  12. Ito, H., Sommer, M. H., Zerboni, L., Baiker, A., Sato, B., Liang, R., Hay, J., Ruyechan, W. & Arvin, A. M. ( 2005; ). Role of the varicella-zoster virus gene product encoded by open reading frame 35 in viral replication in vitro and in differentiated human skin and T cells in vivo. J Virol 79, 4819–4827.[CrossRef]
    [Google Scholar]
  13. Jacobson, J. G., Martin, S. L. & Coen, D. M. ( 1989; ). A conserved open reading frame that overlaps the herpes simplex virus thymidine kinase gene is important for viral growth in cell culture. J Virol 63, 1839–1843.
    [Google Scholar]
  14. Jacobson, J. G., Chen, S. H., Cook, W. J., Kramer, M. F. & Coen, D. M. ( 1998; ). Importance of the herpes simplex virus UL24 gene for productive ganglionic infection in mice. Virology 242, 161–169.[CrossRef]
    [Google Scholar]
  15. Johnston, J. A., Ward, C. L. & Kopito, R. R. ( 1998; ). Aggresomes: a cellular response to misfolded proteins. J Cell Biol 143, 1883–1898.[CrossRef]
    [Google Scholar]
  16. Knipe, D. M., Howley, P. M., Griffin, D. E., Lamb, R. A. & Martin, M. A. ( 2007; ). Fields Virology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins.
  17. Knizewski, L., Kinch, L., Grishin, N. V., Rychlewski, L. & Ginalski, K. ( 2006; ). Human herpesvirus 1 UL24 gene encodes a potential PD-(D/E)XK endonuclease. J Virol 80, 2575–2577.[CrossRef]
    [Google Scholar]
  18. Lomonte, P. & Morency, E. ( 2007; ). Centromeric protein CENP-B proteasomal degradation induced by the viral protein ICP0. FEBS Lett 581, 658–662.[CrossRef]
    [Google Scholar]
  19. Lomonte, P., Sullivan, K. F. & Everett, R. D. ( 2001; ). Degradation of nucleosome-associated centromeric histone H3-like protein CENP-A induced by herpes simplex virus type 1 protein ICP0. J Biol Chem 276, 5829–5835.[CrossRef]
    [Google Scholar]
  20. Lymberopoulos, M. H. & Pearson, A. ( 2007; ). Involvement of UL24 in herpes-simplex-virus-1-induced dispersal of nucleolin. Virology 363, 397–409.[CrossRef]
    [Google Scholar]
  21. Maul, G. G., Guldner, H. H. & Spivack, J. G. ( 1993; ). Modification of discrete nuclear domains induced by herpes simplex virus type 1 immediate early gene 1 product (ICP0). J Gen Virol 74, 2679–2690.[CrossRef]
    [Google Scholar]
  22. Maul, G. G., Ishov, A. M. & Everett, R. D. ( 1996; ). Nuclear domain 10 as preexisting potential replication start sites of herpes simplex virus type-1. Virology 217, 67–75.[CrossRef]
    [Google Scholar]
  23. Mongelard, F. & Bouvet, P. ( 2007; ). Nucleolin: a multiFACeTed protein. Trends Cell Biol 17, 80–86.[CrossRef]
    [Google Scholar]
  24. Monier, K., Armas, J. C., Etteldorf, S., Ghazal, P. & Sullivan, K. F. ( 2000; ). Annexation of the interchromosomal space during viral infection. Nat Cell Biol 2, 661–665.[CrossRef]
    [Google Scholar]
  25. Nascimento, R. & Parkhouse, R. M. ( 2007; ). Murine gammaherpesvirus 68 ORF20 induces cell-cycle arrest in G2 by inhibiting the Cdc2-cyclin B complex. J Gen Virol 88, 1446–1453.[CrossRef]
    [Google Scholar]
  26. Pearson, A. & Coen, D. M. ( 2002; ). Identification, localization, and regulation of expression of the UL24 protein of herpes simplex virus type 1. J Virol 76, 10821–10828.[CrossRef]
    [Google Scholar]
  27. Rickards, B., Flint, S. J., Cole, M. D. & LeRoy, G. ( 2007; ). Nucleolin is required for RNA polymerase I transcription in vivo. Mol Cell Biol 27, 937–948.[CrossRef]
    [Google Scholar]
  28. Rogalski, A. A. & Singer, S. J. ( 1984; ). Associations of elements of the Golgi apparatus with microtubules. J Cell Biol 99, 1092–1100.[CrossRef]
    [Google Scholar]
  29. Scott, E. S. & O'Hare, P. ( 2001; ). Fate of the inner nuclear membrane protein lamin B receptor and nuclear lamins in herpes simplex virus type 1 infection. J Virol 75, 8818–8830.[CrossRef]
    [Google Scholar]
  30. Simpson-Holley, M., Baines, J., Roller, R. & Knipe, D. M. ( 2004; ). Herpes simplex virus 1 UL31 and UL34 gene products promote the late maturation of viral replication compartments to the nuclear periphery. J Virol 78, 5591–5600.[CrossRef]
    [Google Scholar]
  31. Stenberg, R. M. & Pizer, L. I. ( 1982; ). Herpes simplex virus-induced changes in cellular and adenovirus RNA metabolism in an adenovirus type 5-transformed human cell line. J Virol 42, 474–487.
    [Google Scholar]
  32. Turcotte, S., Letellier, J. & Lippe, R. ( 2005; ). Herpes simplex virus type 1 capsids transit by the trans-Golgi network, where viral glycoproteins accumulate independently of capsid egress. J Virol 79, 8847–8860.[CrossRef]
    [Google Scholar]
  33. Uprichard, S. L. & Knipe, D. M. ( 1997; ). Assembly of herpes simplex virus replication proteins at two distinct intranuclear sites. Virology 229, 113–125.[CrossRef]
    [Google Scholar]
  34. von Messling, V., Springfeld, C., Devaux, P. & Cattaneo, R. ( 2003; ). A ferret model of canine distemper virus virulence and immunosuppression. J Virol 77, 12579–12591.[CrossRef]
    [Google Scholar]
  35. Wagner, E. K. & Roizman, B. ( 1969; ). Ribonucleic acid synthesis in cells infected with herpes simplex virus. I. Patterns of ribonucleic acid synthesis in productively infected cells. J Virol 4, 36–46.
    [Google Scholar]
  36. Wang, S. K., Duh, C. Y. & Chang, T. T. ( 2000; ). Cloning and identification of regulatory gene UL76 of human cytomegalovirus. J Gen Virol 81, 2407–2416.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.83573-0
Loading
/content/journal/jgv/10.1099/vir.0.83573-0
Loading

Data & Media loading...

Supplements

vol. , part 5, pp. 1142 - 1151

Intracellular localization of HA–UL24 over a range of plasmid DNA transfected

Primer sequences [Single PDF file](138 KB)



PDF

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