1887

Abstract

Herpes simplex virus type 1 (HSV-1) strain McKrae is neurovirulent in rabbits infected by the ocular route, causing fatal encephalitis in approximately 50% of the animals, and has a high-level spontaneous reactivation phenotype, with 10% of rabbit eyes containing reactivated virus at any given time. In contrast, HSV-1 strain KOS is completely avirulent (no rabbits die) and has a completely negative spontaneous reactivation phenotype. Mutations of the ICP34.5 gene can reduce the neurovirulence of HSV-1 strains McKrae and 17syn by up to 100000-fold. ICP34.5 mutants also have reduced spontaneous reactivation phenotypes. To determine whether differences in the ICP34.5 gene might be involved in the reduced neurovirulence and spontaneous reactivation phenotypes of KOS compared with McKrae, we constructed chimeric viruses containing the KOS ICP34.5 gene in place of the McKrae ICP34.5 gene. Rabbits ocularly infected with the chimeric viruses had a high spontaneous reactivation phenotype indistinguishable from McKrae. In contrast, neurovirulence of the chimeric viruses was decreased compared with McKrae. Thus, one or more ‘defects’ in the KOS ICP34.5 gene appeared to be at least partially responsible for the reduced neurovirulence of KOS compared with McKrae. However, there appeared to be no ‘defect′ in the KOS ICP34.5 function required for efficient spontaneous reactivation.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-83-12-2933
2002-12-01
2019-10-20
Loading full text...

Full text loading...

/deliver/fulltext/jgv/83/12/0832933a.html?itemId=/content/journal/jgv/10.1099/0022-1317-83-12-2933&mimeType=html&fmt=ahah

References

  1. Cameron, J. M., McDougall, I., Marsden, H. S., Preston, V. G., Ryan, D. M. & Subak-Sharpe, J. H. ( 1988; ). Ribonucleotide reductase encoded by herpes simplex virus is a determinant of the pathogenicity of the virus in mice and a valid antiviral target. Journal of General Virology 69, 2607-2612.[CrossRef]
    [Google Scholar]
  2. Chou, J. & Roizman, B. ( 1992; ). The gamma 1(34.5) gene of herpes simplex virus 1 precludes neuroblastoma cells from triggering total shutoff of protein synthesis characteristic of programmed cell death in neuronal cells. Proceedings of the National Academy of Sciences, USA 89, 3266-3270.[CrossRef]
    [Google Scholar]
  3. Chou, J., Poon, A. P., Johnson, J. & Roizman, B. ( 1994; ). Differential response of human cells to deletions and stop codons in the gamma(1)34.5 gene of herpes simplex virus. Journal of Virology 68, 8304-8311.
    [Google Scholar]
  4. Dobson, A. T., Sederati, F., Devi-Rao, G., Flanagan, W. M., Farrell, M. J., Stevens, J. G., Wagner, E. K. & Feldman, L. T. ( 1989; ). Identification of the latency-associated transcript promoter by expression of rabbit beta-globin mRNA in mouse sensory nerve ganglia latently infected with a recombinant herpes simplex virus. Journal of Virology 63, 3844-3851.
    [Google Scholar]
  5. Drolet, B. S., Perng, G. C., Cohen, J., Slanina, S. M., Yukht, A., Nesburn, A. B. & Wechsler, S. L. ( 1998; ). The region of the herpes simplex virus type 1 LAT gene involved in spontaneous reactivation does not encode a functional protein. Virology 242, 221-232.[CrossRef]
    [Google Scholar]
  6. Farrell, M. J., Dobson, A. T. & Feldman, L. T. ( 1991; ). Herpes simplex virus latency-associated transcript is a stable intron. Proceedings of the National Academy of Sciences, USA 88, 790-794.[CrossRef]
    [Google Scholar]
  7. Gordon, Y. J., Simon, P. L. & Armstrong, J. A. ( 1984; ). Neurovirulence of an herpes simplex type 1 thymidine kinase negative mutant determined by virus biochemical defect and host immune system in mice. Brief report. Archives of Virology 80, 225-229.[CrossRef]
    [Google Scholar]
  8. Hill, J. M., Rayfield, M. A. & Haruta, Y. ( 1987; ). Strain specificity of spontaneous and adrenergically induced HSV-1 ocular reactivation in latently infected rabbits. Current Eye Research 6, 91-97.[CrossRef]
    [Google Scholar]
  9. Kosovsky, J., Vojvodova, A., Oravcova, I., Kudelova, M., Matis, J. & Rajcani, J. ( 2000; ). Herpes simplex virus 1 (HSV-1) strain HSZP glycoprotein B gene: comparison of mutations among strains differing in virulence. Virus Genes 20, 27-33.[CrossRef]
    [Google Scholar]
  10. Kostal, M., Bacik, I., Rajcani, J. & Kaerner, H. C. ( 1994; ). Replacement of glycoprotein B gene in the herpes simplex virus type 1 strain ANGpath DNA by that originating from nonpathogenic strain KOS reduces the pathogenicity of recombinant virus. Acta Virologica 38, 77-88.
    [Google Scholar]
  11. Kurachi, R., Daikoku, T., Tsurumi, T., Maeno, K., Nishiyama, Y. & Kurata, T. ( 1993; ). The pathogenicity of a US3 protein kinase-deficient mutant of herpes simplex virus type 2 in mice. Archives of Virology 133, 259-273.[CrossRef]
    [Google Scholar]
  12. McGeoch, D. J. ( 1987; ). The genome of herpes simplex virus: structure, replication and evolution. Journal of Cell Science Supplement 7, 67-94.
    [Google Scholar]
  13. Mao, H. & Rosenthal, K. S. ( 2002; ). An N-terminal arginine-rich cluster and a proline–alanine–threonine repeat region determine the cellular localization of the herpes simplex virus type 1 ICP34.5 protein and its ligand, protein phosphatase 1. Journal of Biological Chemistry 277, 11423-11431.[CrossRef]
    [Google Scholar]
  14. Perng, G. C., Dunkel, E. C., Geary, P. A., Slanina, S. M., Ghiasi, H., Kaiwar, R., Nesburn, A. B. & Wechsler, S. L. ( 1994; ). The latency-associated transcript gene of herpes simplex virus type 1 (HSV-1) is required for efficient in vivo spontaneous reactivation of HSV-1 from latency. Journal of Virology 68, 8045-8055.
    [Google Scholar]
  15. Perng, G. C., Thompson, R. L., Sawtell, N. M., Taylor, W. E., Slanina, S. M., Ghiasi, H., Kaiwar, R., Nesburn, A. B. & Wechsler, S. L. ( 1995; ). An avirulent ICP34.5 deletion mutant of herpes simplex virus type 1 is capable of in vivo spontaneous reactivation. Journal of Virology 69, 3033-3041.
    [Google Scholar]
  16. Perng, G. C., Chokephaibulkit, K., Thompson, R. L., Sawtell, N. M., Slanina, S. M., Ghiasi, H., Nesburn, A. B. & Wechsler, S. L. ( 1996a; ). The region of the herpes simplex virus type 1 LAT gene that is colinear with the ICP34.5 gene is not involved in spontaneous reactivation. Journal of Virology 70, 282-291.
    [Google Scholar]
  17. Perng, G. C., Ghiasi, H., Slanina, S. M., Nesburn, A. B. & Wechsler, S. L. ( 1996b; ). High-dose ocular infection with a herpes simplex virus type 1 ICP34.5 deletion mutant produces no corneal disease or neurovirulence yet results in wild-type levels of spontaneous reactivation. Journal of Virology 70, 2883-2893.
    [Google Scholar]
  18. Perng, G. C., Ghiasi, H., Slanina, S. M., Nesburn, A. B. & Wechsler, S. L. ( 1996c; ). The spontaneous reactivation function of the herpes simplex virus type 1 LAT gene resides completely within the first 1·5 kilobases of the 8·3-kilobase primary transcript. Journal of Virology 70, 976-984.
    [Google Scholar]
  19. Perng, G. C., Slanina, S. M., Yuhkt, A., Drolet, B. S., Keleher, W. J., Ghiasi, H., Nesburn, A. B. & Wechsler, S. L. ( 1999; ). A herpes simplex virus type 1 latency associated transcript (LAT) mutant with increased virulence and reduced spontaneous reactivation. Journal of Virology 73, 920-929.
    [Google Scholar]
  20. Perry, L. J. & McGeoch, D. J. ( 1988; ). The DNA sequences of the long repeat region and adjoining parts of the long unique region in the genome of herpes simplex virus type 1. Journal of General Virology 69, 2831-2846.[CrossRef]
    [Google Scholar]
  21. Rock, D. L., Nesburn, A. B., Ghiasi, H., Ong, J., Lewis, T. L., Lokensgard, J. R. & Wechsler, S. L. ( 1987; ). Detection of latency-related viral RNAs in trigeminal ganglia of rabbits latently infected with herpes simplex virus type 1. Journal of Virology 61, 3820-3826.
    [Google Scholar]
  22. Stevens, J. G., Wagner, E. K., Devi-Rao, G. B., Cook, M. L. & Feldman, L. T. ( 1987; ). RNA complementary to a herpesvirus alpha gene mRNA is prominent in latently infected neurons. Science 235, 1056-1059.[CrossRef]
    [Google Scholar]
  23. Thompson, R. L. & Wagner, E. K. ( 1988; ). Partial rescue of herpes simplex virus neurovirulence with a 3·2 kb cloned DNA fragment. Virus Genes 1, 261-273.[CrossRef]
    [Google Scholar]
  24. Thompson, R. L., Wagner, E. K. & Stevens, J. G. ( 1983; ). Physical location of a herpes simplex virus type-1 gene function(s) specifically associated with a 10 million-fold increase in HSV neurovirulence. Virology 131, 180-192.[CrossRef]
    [Google Scholar]
  25. Yuhasz, S. A. & Stevens, J. G. ( 1993; ). Glycoprotein B is a specific determinant of herpes simplex virus type 1 neuroinvasiveness. Journal of Virology 67, 5948-5954.
    [Google Scholar]
  26. Zwaagstra, J. C., Ghiasi, H., Slanina, S. M., Nesburn, A. B., Wheatley, S. C., Lillycrop, K., Wood, J., Latchman, D. S., Patel, K. & Wechsler, S. L. ( 1990; ). Activity of herpes simplex virus type 1 latency-associated transcript (LAT) promoter in neuron-derived cells: evidence for neuron specificity and for a large LAT transcript. Journal of Virology 64, 5019-5028.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-83-12-2933
Loading
/content/journal/jgv/10.1099/0022-1317-83-12-2933
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