1887

Abstract

The gene of herpes simplex virus 1 (HSV-1) is widely conserved among all subfamilies of the . It is one of only four HSV-1 genes for which mutations have been mapped that confer a syncytial plaque phenotype. In a mouse model of infection, UL24-deficient viruses exhibit reduced titres, particularly in neurons, and an apparent defect in reactivation from latency. There are several highly conserved residues in UL24; however, their importance in the role of UL24 is unknown. In this study, we compared virus strains with substitution mutations corresponding to the PD-(D/E)XK endonuclease motif of UL24 (vUL24-E99A/K101A) or a substitution of another highly conserved residue (vUL24-G121A). Both mutant viruses cause the formation of syncytial plaques at 39 °C; however, we found that the viruses differed dramatically when tested in a mouse model of infection. vUL24-E99A/K101A exhibited titres in the eye that were 10-fold lower than those of the wild-type virus KOS, and titres in trigeminal ganglia (TG) that were more than 2 log lower. Clinical signs were barely detectable with vUL24-E99A/K101A. Furthermore, the percentage of TG from which virus reactivated was also significantly lower for this mutant than for KOS. In contrast, vUL24-G121A behaved similarly to the wild-type virus in mice. These results are consistent with the endonuclease motif being important for the role of UL24 and also imply that the UL24 temperature-dependent syncytial plaque phenotype can be separated genetically from several phenotypes.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.017921-0
2010-05-01
2021-10-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/91/5/1109.html?itemId=/content/journal/jgv/10.1099/vir.0.017921-0&mimeType=html&fmt=ahah

References

  1. Baines, J. D., Ward, P. L., Campadelli-Fiume, G. & Roizman, B.(1991). The UL20 gene of herpes simplex virus 1 encodes a function necessary for viral egress. J Virol 65, 6414–6424. [Google Scholar]
  2. Bertrand, L. & Pearson, A.(2008). The conserved N-terminal domain of herpes simplex virus 1 UL24 protein is sufficient to induce the spatial redistribution of nucleolin. J Gen Virol 89, 1142–1151.[CrossRef] [Google Scholar]
  3. Bertrand, L., Leiva-Torres, G. A., Hyjazie, H. & Pearson, A.(2010). Conserved residues in the UL24 protein of herpes simplex virus 1 are important for the dispersal of the nucleolar protein nucleolin. J Virol 84, 109–118.[CrossRef] [Google Scholar]
  4. 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]
  5. Calistri, A., Sette, P., Salata, C., Cancellotti, E., Forghieri, C., Comin, A., Gottlinger, H., Campadelli-Fiume, G., Palu, G. & Parolin, C.(2007). Intracellular trafficking and maturation of herpes simplex virus type 1 gB and virus egress require functional biogenesis of multivesicular bodies. J Virol 81, 11468–11478.[CrossRef] [Google Scholar]
  6. Chen, S. H., Pearson, A., Coen, D. M. & Chen, S. H.(2004). Failure of thymidine kinase-negative herpes simplex virus to reactivate from latency following efficient establishment. J Virol 78, 520–523.[CrossRef] [Google Scholar]
  7. Coen, D. M., Weinheimer, S. P. & McKnight, S. L.(1986). A genetic approach to promoter recognition during trans induction of viral gene expression. Science 234, 53–59.[CrossRef] [Google Scholar]
  8. Coen, D. M., Kosz-Vnenchak, M., Jacobson, J. G., Leib, D. A., Bogard, C. L., Schaffer, P. A., Tyler, K. L. & Knipe, D. M.(1989). Thymidine kinase-negative herpes simplex virus mutants establish latency in mouse trigeminal ganglia but do not reactivate. Proc Natl Acad Sci U S A 86, 4736–4740.[CrossRef] [Google Scholar]
  9. Davar, G., Kramer, M. F., Garber, D., Roca, A. L., Andersen, J. K., Bebrin, W., Coen, D. M., Kosz-Vnenchak, M., Knipe, D. M. & other authors(1994). Comparative efficacy of expression of genes delivered to mouse sensory neurons with herpes virus vectors. J Comp Neurol 339, 3–11.[CrossRef] [Google Scholar]
  10. Davido, D. J. & Leib, D. A.(1996). Role of cis-acting sequences of the ICP0 promoter of herpes simplex virus type 1 in viral pathogenesis, latency and reactivation. J Gen Virol 77, 1853–1863.[CrossRef] [Google Scholar]
  11. Davison, A. J.(2002). Evolution of the herpesviruses. Vet Microbiol 86, 69–88.[CrossRef] [Google Scholar]
  12. Foster, T. P. & Kousoulas, K. G.(1999). Genetic analysis of the role of herpes simplex virus type 1 glycoprotein K in infectious virus production and egress. J Virol 73, 8457–8468. [Google Scholar]
  13. Foster, T. P., Alvarez, X. & Kousoulas, K. G.(2003). Plasma membrane topology of syncytial domains of herpes simplex virus type 1 glycoprotein K (gK): the UL20 protein enables cell surface localization of gK but not gK-mediated cell-to-cell fusion. J Virol 77, 499–510.[CrossRef] [Google Scholar]
  14. Foster, T. P., Melancon, J. M., Baines, J. D. & Kousoulas, K. G.(2004). The herpes simplex virus type 1 UL20 protein modulates membrane fusion events during cytoplasmic virion morphogenesis and virus-induced cell fusion. J Virol 78, 5347–5357.[CrossRef] [Google Scholar]
  15. Fuchs, W., Klupp, B. G., Granzow, H. & Mettenleiter, T. C.(1997). The UL20 gene product of pseudorabies virus functions in virus egress. J Virol 71, 5639–5646. [Google Scholar]
  16. 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]
  17. Hutchinson, L. & Johnson, D. C.(1995). Herpes simplex virus glycoprotein K promotes egress of virus particles. J Virol 69, 5401–5413. [Google Scholar]
  18. 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]
  19. 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]
  20. 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]
  21. Jayachandra, S., Baghian, A. & Kousoulas, K. G.(1997). Herpes simplex virus type 1 glycoprotein K is not essential for infectious virus production in actively replicating cells but is required for efficient envelopment and translocation of infectious virions from the cytoplasm to the extracellular space. J Virol 71, 5012–5024. [Google Scholar]
  22. 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]
  23. Leib, D. A., Bogard, C. L., Kosz-Vnenchak, M., Hicks, K. A., Coen, D. M., Knipe, D. M. & Schaffer, P. A.(1989). A deletion mutant of the latency-associated transcript of herpes simplex virus type 1 reactivates from the latent state with reduced frequency. J Virol 63, 2893–2900. [Google Scholar]
  24. 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]
  25. Melancon, J. M., Luna, R. E., Foster, T. P. & Kousoulas, K. G.(2005). Herpes simplex virus type 1 gK is required for gB-mediated virus-induced cell fusion, while neither gB and gK nor gB and UL20p function redundantly in virion de-envelopment. J Virol 79, 299–313.[CrossRef] [Google Scholar]
  26. Mott, K. R., Bresee, C. J., Allen, S. J., BenMohamed, L., Wechsler, S. L. & Ghiasi, H.(2009). Level of herpes simplex virus type 1 latency correlates with severity of corneal scarring and exhaustion of CD8+ T cells in trigeminal ganglia of latently infected mice. J Virol 83, 2246–2254.[CrossRef] [Google Scholar]
  27. 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]
  28. Nascimento, R., Dias, J. D. & Parkhouse, R. M.(2009). The conserved UL24 family of human alpha, beta and gamma herpesviruses induces cell cycle arrest and inactivation of the cyclinB/cdc2 complex. Arch Virol 154, 1143–1149.[CrossRef] [Google Scholar]
  29. 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]
  30. Sanders, P. G., Wilkie, N. M. & Davison, A. J.(1982). Thymidine kinase deletion mutants of herpes simplex virus type 1. J Gen Virol 63, 277–295.[CrossRef] [Google Scholar]
  31. Spear, P. G.(1993). Membrane fusion induced by herpes simplex virus. In Viral Fusion Mechanisms, pp. 201–232. Edited by J. Bentz. Boca Raton, FL: CRC Press.
  32. Spear, P. G. & Longnecker, R.(2003). Herpesvirus entry: an update. J Virol 77, 10179–10185.[CrossRef] [Google Scholar]
  33. Tognon, M., Guandalini, R., Romanelli, M. G., Manservigi, R. & Trevisani, B.(1991). Phenotypic and genotypic characterization of locus Syn 5 in herpes simplex virus 1. Virus Res 18, 135–150.[CrossRef] [Google Scholar]
  34. Wright, C. C., Wisner, T. W., Hannah, B. P., Eisenberg, R. J., Cohen, G. H. & Johnson, D. C.(2009). Fusion between perinuclear virions and the outer nuclear membrane requires the fusogenic activity of herpes simplex virus gB. J Virol 83, 11847–11856.[CrossRef] [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.017921-0
Loading
/content/journal/jgv/10.1099/vir.0.017921-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

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