1887

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Volume 75, Issue 8

Reactivation of latent herpes simplex virus from explanted dorsal root ganglia Free

Abstract

Reactivation was induced by explantation of dorsal root ganglia (DRG) from mice that were latently infected with herpes simplex virus type 1. Reactivation was first detected, using combined hybridization and immunocytochemistry, at 2 or 3 days post-explantation (p.e.). Evidence of reactivation was found primarily in neurons that did not also contain latency-associated transcripts (LATs). Occasionally, mRNA of immediate early gene 2 (IE2) or IE4/5, in the absence of other viral mRNAs or antigen, was found in LAT neurons. Thus, if reactivation was occurring in LAT neurons, the LATs must have been lost as an early consequence; however we could detect neither a decrease in the percentages of LAT neurons nor a reduction in the intensity of the LAT signal during the period of reactivation. However, the number of foci of reactivation was generally less than 2·9% of the estimated number of LAT cells in the DRG; this may account for our failure to see such changes. A redistribution of the LATs into the cytoplasm was found in some cells but this could reflect the poor survival and consequent death of the explanted neurons. We conclude that the majority of LAT neurons did not reactivate on explantation and that if reactivation occurred only in LAT neurons, the LATs must have been removed from the nucleus as an early consequence of reactivation. Alternatively, there may be a population of latently infected cells that do not express LATs.

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  • Accepted:
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© The Journal of General Virology 1994
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1994-08-01
2024-05-10
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References

  1. Ace C. I., Dalrymple M. A., Ramsay F. H., Preston V. G., Preston C. M. 1988; Mutational analysis of the herpes simplex virus type 1 trans-inducing factor Vmw65. Journal of Virology 69:2595–2605
     [Google Scholar]
  2. Ace C. I., Mckee T. A., Ryan J, Cameron J. M., Preston C. M. 1989; Construction and characterization of a herpes simplex virus type 1 mutant unable to transinduce immediate-early gene expression. Journal of Virology 63:2260–2269
     [Google Scholar]
  3. Arvidsson J., Ygge J., Grant G. 1986; Cell loss in lumbar dorsal root ganglia and transganglionic degeneration after sciatic nerve resection in the rat. Brain Research 373:15–21
     [Google Scholar]
  4. Batchelor A. H., O’Hare P. 1990; Regulation and cell type-specific activity of a promoter located upstream of the latency-associated transcript of herpes simplex virus type 1. Journal of Virology 64:3269–3279
     [Google Scholar]
  5. Block T. M., Spivack J. G., Steiner I., Deshmane S., Mcintosh M. T., Lirette R. P., Fraser N. W. 1990; A herpes simplex virus type 1 latency-associated transcript mutant reactivates with normal latencies from latent infection. Journal of Virology 64:3417–3426
     [Google Scholar]
  6. Brown S. M., Ritchie D. A., subak-Sharpe J. H. 1973; Genetic studies with herpes simplex virus type 1. The isolation of temperature-sensitive mutants, their arrangement into complementation groups and recombination analysis leading to a linkage map. Journal of General Virology 18:329–346
     [Google Scholar]
  7. Deshmane S. L., Nicosia M., Valyi-Nagy T., Feldman L. T., Dillner A., Fraser N. W. 1993; An HSV-1 mutant lacking the LAT TATA element reactivates normally in explant cocultivation. Virology 196:868–872
     [Google Scholar]
  8. Disbrey B. D., Rack J. H. 1970 Histological Laboratory Methods Edinburgh & London: Churchill Livingstone;
     [Google Scholar]
  9. Dobson A. T., Sedarati 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]
  10. Doerig C., Pizer L. I., Wilcox C. L. 1991; An antigen encoded by the latency-associated transcript in neuronal cell cultures latently infected with herpes simplex virus type 1. Journal of Virology 65:2724–2727
     [Google Scholar]
  11. Ecob-Prince M. S., Preston C. M., Rixon F. J., Hassan K., Kennedy P. G. E. 1993a; Neurons containing latency-associated transcripts are numerous and widespread in dorsal root ganglia following footpad inoculation of mice with herpes simplex virus type 1 mutant ml 814. Journal of General Virology 74:985–994
     [Google Scholar]
  12. Ecob-Prince M. S., Rixon F. J., Preston C. M., Hassan K., Kennedy P. G. E. 1993b; Reactivation in vivo and in vitro of herpes simplex virus from mouse dorsal root ganglia which contain different levels of latency-associated transcripts. Journal of General Virology 74:995–1002
     [Google Scholar]
  13. 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, U.S.A 88:790–794
     [Google Scholar]
  14. Fraser N. W., Block T. M., Spivack J. G. 1992; The latency-associated transcripts of herpes simplex virus: RNA in search of function. Virology 191:1–8
     [Google Scholar]
  15. Griffiths I. R., Mitchell L. S., Mcphilemy K., Morrison S., Kyriakides E., Barrie J. A. 1989; Expression of myelin protein genes in Schwann cells. Journal of Neurocytology 18:345–352
     [Google Scholar]
  16. Hill J. M., Sedarati F., Javier R. T., Wagner E. K., Stevens J. G. 1990; Herpes simplex virus latent phase transcription facilitates in vivo reactivation. Virology 174:117–125
     [Google Scholar]
  17. Ho D. Y., Mocarski E. S. 1989; Herpes simplex virus latent RNA (LAT) is not required for latent infection in the mouse. Proceedings of the National Academy of Sciences, U.S.A 86:7596–7600
     [Google Scholar]
  18. 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 1 reactivates from the latent state with reduced frequency. Journal of Virology 63:2893–2900
     [Google Scholar]
  19. Mcfarlane M., Daksis J. I., Preston C. M. 1992; Hexamethylenebisacetamide stimulates herpes simplex virus immediate early gene expression in the absence of trans-induction by Vmw65. Journal of General Virology 73:285–292
     [Google Scholar]
  20. Mclennan J. L., Darby G. 1980; Herpes simplex virus latency: the cellular location of virus in dorsal root ganglia and the fate of the infected cell following virus activation. Journal of General Virology 51:233–243
     [Google Scholar]
  21. Maddox P. H., Jenkins D. 1987; 3 Aminopropyltriethoxysilane (APES): a new advance in section adhesion. Journal of Clinical Pathology 40:1256–1260
     [Google Scholar]
  22. Mitchell W. J., Lirette R. P., Fraser N. W. 1990; Mapping of low abundance latency-associated RNA in the trigeminal ganglia of mice latently infected with herpes simplex virus type 1. Journal of General Virology 71:125–132
     [Google Scholar]
  23. Nicholson P. 1992 Analysis offour capsid protein genes of HSV-1 Ph.D. thesis University of Glasgow:
     [Google Scholar]
  24. 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
     [Google Scholar]
  25. Rader K. A., Ackland-Berglund C. E., Miller J. K., Pepose J. S., Leib D. A. 1993; In vivo characterization of site-directed mutations in the promoter of the herpes simplex virus type 1 latency-associated transcripts. Journal of General Virology 74:1859–1869
     [Google Scholar]
  26. 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]
  27. Rødahl E., Stevens J. G. 1992; Differential accumulation of herpes simplex virus type 1 latency-associated transcripts in sensory and autonomic ganglia. Virology 189:385–388
     [Google Scholar]
  28. Sawtell N. M., Thompson R. L. 1992; Herpes simplex virus type 1 latency-associated transcription unit promotes anatomical site- dependent establishment and reactivation from latency. Journal of Virology 66:2157–2169
     [Google Scholar]
  29. Spivack J. G., Fraser N. W. 1987; Detection of herpes simplex virus type 1 transcripts during latent infection in mice. Journal of Virology 61:3841–3847
     [Google Scholar]
  30. Spivack J. G., Fraser N. W. 1988; Expression of herpes simplex virus type 1 (HSV-1) latency-associated transcripts and transcripts affected by the deletion in avirulent mutant HFEM: evidence for a new class of genes. Journal of Virology 62:3281–3287
     [Google Scholar]
  31. Spivack J. G., Woods G. M., Fraser N. W. 1991; Identification of a novel latency specific splice donor signal within the herpes simplex virus type 1 2·0 kilobase latency-associated transcript (LAT): translation inhibition of LAT open reading frames by the intron within the 2·0 kilobase LAT. Journal of Virology 65:6800–6810
     [Google Scholar]
  32. Steiner I., Spivack J. G., Lirette R. P., Brown S. M., Maclean A. R., subak-Sharpe J. H., Fraser N. W. 1989; Herpes simplex virus type 1 latency-associated transcripts are evidently not essential for latent infection. EMBO Journal 8:505–511
     [Google Scholar]
  33. Steiner I., Spivack J. G., Deshmane S. L., Ace C. I., Preston C. M., Fraser N. W. 1990; A herpes simplex virus type 1 mutant containing a non-transducing Vmw65 protein establishes latent infection in vivo in the absence of viral replication and reactivates efficiently from explanted trigeminal ganglia. Journal of Virology 64:1630–1638
     [Google Scholar]
  34. Stevens J. G., Wagner E. K., Devi-Rao G. B., Cook M. L., Feldman L. T. 1987; RNA complementary to a herpesvirus a- gene mRNA is prominent in latently infected neurons. Science 235:1056–1059
     [Google Scholar]
  35. Tenser R. B., Edris W. A., Hay K. A. 1988; Herpes simplex virus latent infection: reactivation and elimination of latency after neurectomy. Virology 167:302–305
     [Google Scholar]
  36. Tenser R. B., Edris W. A., Hay K. A. 1993; Neuronal control of herpes simplex virus latency. Virology 195:337–347
     [Google Scholar]
  37. Trousdale M. D., Steiner I., Spivack J. G., Deshmane S. L., Brown S. M., Maclean A. R., subak-Sharpe J. H., Fraser N. W. 1991; In vivo and in vitro reactivation impairment of a herpes simplex virus type 1 latency-associated transcription variant in a rabbit eye model. Journal of Virology 65:6989–6993
     [Google Scholar]
  38. Wagner E. K., Flanagan M. W., Devi-Rao G., Zhang Y. F., Hill J. M., Anderson K. P., Stevens J. G. 1988; The herpes simplex virus latency-associated transcript is spliced during the latent phase of infection. Journal of Virology 62:4577–4585
     [Google Scholar]
  39. Walz M. A., Price R. W., Notkins A. L. 1974; Latent ganglionic infection with herpes simplex virus types 1 and 2: viral reactivation in vivo after neurectomy. Science 184:1185–1187
     [Google Scholar]
  40. Wechsler S. L., Nesburn A. B., Watson R., Slanina S., Ghiasi H. 1988; Fine mapping of the major latency-related RNA of herpes simplex virus type 1 in humans. Journal of General Virology 69:3101–3106
     [Google Scholar]
  41. Wong J., Oblinger M. M. 1991; NGF rescues substance P but not neurofilament or tubulin gene expression in axotomized sensory neurons. Journal of Neuroscience 11:543–552
     [Google Scholar]
  42. Ygge J. 1989; Neuronal loss in lumbar dorsal root ganglia after proximal compared to distal sciatic nerve resection: a quantitative study in the rat. Brain Research 478:193–195
     [Google Scholar]
  43. Zwaagstra J., 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 type 1 latency associated transcript (LAT) promoter in neuron-derived cells: evidence of neuron specificity and for a large LAT transcript. Journal of Virology 64:5019–5028
     [Google Scholar]
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Reactivation of latent herpes simplex virus from explanted dorsal root ganglia
J. Gen. Virol. 75, 2017 (1994); https://doi.org/10.1099/0022-1317-75-8-2017
/content/journal/jgv/10.1099/0022-1317-75-8-2017
/content/journal/jgv/10.1099/0022-1317-75-8-2017
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