1887

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Volume 80, Issue 5

An analysis of herpes simplex virus gene expression during latency establishment and reactivation Free

Abstract

In order to facilitate an analysis of the pattern of herpes simplex virus gene expression during latency establishment and reactivation, recombinant viruses containing the lacZ reporter gene under control of either the immediate early 110 (IE110) promoter or the latency-associated promoter have been constructed. Histochemical staining of ganglia taken from mice infected with these viruses allows for the rapid identification and quantification of sensory neurones in which these two promoters are active. Using the mouse ear model, this study demonstrates that, during the establishment of latency in vivo, IE110 promoter activity is only detectable in ganglia which provide innervation to the site of virus inoculation. Latency, however, is efficiently established not only in these ganglia, but also in adjacent ganglia whose neurones do not innervate the ear, and in which there was no evidence of IE110 expression during the acute phase of infection. This implies that replication-competent virus can efficiently establish latency in the absence of detectable IE110 expression. In addition, it has been possible to investigate viral gene expression in neurones following ganglionic explant culture by monitoring IE110 promoter-driven lacZ expression within reactivating neurones. This study shows that virus can be reactivated from all latently infected ganglia, but that reactivation appears to be more efficient from ganglia which provide innervation to the site of infection. The implications of these results for the mechanisms involved in latency establishment and reactivation are discussed.

  • Received:
  • Accepted:
  • Published Online:
© Journal of General Virology 1999
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1999-05-01
2024-04-20
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References

  1. Ace C. I., McKee T. A., Ryan J. M., 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]
  2. Arthur J., Efstathiou S., Simmons A. 1993; Intranuclear foci containing low abundance herpes simplex virus latency-associated transcripts visualized by non-isotopic in situ hybridization. Journal of General Virology 74:1363–1370
     [Google Scholar]
  3. Balan P., Davis-Poynter N., Bell S., Atkinson H., Browne H., Minson T. 1994; An analysis of the in vitro and in vivo phenotypes of mutants of herpes simplex virus type 1 lacking glycoproteins gG, gE, gl or the putative gJ. Journal of General Virology 75:1245–1258
     [Google Scholar]
  4. Bloom D. C., Hill J. M., Devi R. G., Wagner E. K., Feldman L. T., Stevens J. G. 1996; A 348 base-pair region in the latency-associated transcript facilitates herpes simplex virus type 1 reactivation. Journal of Virology 70:2449–2459
     [Google Scholar]
  5. Campbell M. E., Palfreyman J. W., Preston C. M. 1984; Identification of herpes simplex virus DNA sequences which encode a transacting polypeptide responsible for stimulation of immediate early transcription. Journal of Molecular Biology 180:1–19
     [Google Scholar]
  6. Chiocca E. A., Choi B. B., Cai W. Z., DeLuca N. A., Schaffer P. A., DiFiglia M., Breakefield X. O., Martuza R. L. 1990; Transfer and expression of the lacZ gene in rat brain neurons mediated by herpes simplex virus mutants. New Biology 2:739–746
     [Google Scholar]
  7. DeLuca N. A., McCarthy A. M., Schaffer P. A. 1985; Isolation and characterization of deletion mutants of herpes simplex virus type 1 in the gene encoding immediate-early regulatory protein ICP4. Journal of Virology 56:558–570
     [Google Scholar]
  8. Ecob-Prince M. S., Preston C. M., Rixon F. J., Hassan K., Kennedy P. G. E. 1993; 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 in1814. Journal of General Virology 74:985–994
     [Google Scholar]
  9. Harris R. A., Preston C. M. 1991; Establishment of latency in vitro by the herpes simplex virus type 1 mutant in 1814. Journal of General Virology 72:907–913
     [Google Scholar]
  10. Hill T.J., Field H.J., Blyth W. A. 1975; Acute and recurrent infection with herpes simplex virus in the mouse: a model for studying latency and recurrent disease. Journal of General Virology 28:341–353
     [Google Scholar]
  11. Hill J. M., Garza H. H., Su Y. -H., Meegalla R., Hanna L. A., Loutsch J. M., Thompson H. W., Varnell E. D., Bloom D. C., Block T. M. 1997; A 437 bp deletion at the beginning of the latency-associated promoter significantly reduced adrenergically induced HSV-1 ocular reactivation in latently infected rabbits. Journal of Virology 71:6555–6559
     [Google Scholar]
  12. Jamieson D. R. S., Robinson L. H., Daksis J. I., Nicholl M. J., Preston C. M. 1995; Quiescent viral genomes in human fibroblasts after infection with herpes simplex virus type 1 Vmw65 mutants. Journal of General Virology 76:1417–1431
     [Google Scholar]
  13. Kosz Vnenchak M., Coen D. M., Knipe D. M. 1990; Restricted expression of herpes simplex virus lytic genes during establishment of latent infection by thymidine kinase-negative mutant viruses. Journal of Virology 64:5396–5402
     [Google Scholar]
  14. Kosz Vnenchak M., Jacobson J., Coen D. M., Knipe D. M. 1993; Evidence for a novel regulatory pathway for herpes simplex virus gene expression in trigeminal ganglion neurons. Journal of Virology 67:5383–5393
     [Google Scholar]
  15. Kristie T. M., Sharp P. A. 1993; Purification of the cellular C1 factor required for the stable recognition of the Oct-1 homeodomain by the herpes simplex virus alpha-trans-induction factor (VP16). Journal of Biological Chemistry 268:6525–6534
     [Google Scholar]
  16. Lachmann R. H., Efstathiou S. 1997; Utilization of the herpes simplex virus type 1 latency-associated regulatory region to drive stable reporter gene expression in the nervous system. Journal of Virology 71:3197–3207
     [Google Scholar]
  17. Leib D. A., Coen D. M., Bogard C. L., Hicks K. A., Yager D. R., Knipe D. M., Tyler K. L., Schaffer P. A. 1989; Immediate-early regulatory gene mutants define different stages in the establishment and reactivation of herpes simplex virus latency. Journal of Virology 63:759–768
     [Google Scholar]
  18. Margolis T. P., Sedarati F., Dobson A. T., Feldman L. T., Stevens J. G. 1992; Pathways of viral gene expression during acute neuronal infection with HSV-1. Virology 189:150–160
     [Google Scholar]
  19. Nichol P. F., Chang J. Y., Johnson E. M., Olivo P. D. 1996; HSVgene expression in neurons : viral DNA synthesis is a critical regulatory event in the branch point between the lytic and the latent pathways. Journal of Virology 70:5476–5486
     [Google Scholar]
  20. O’Hare P., Goding C. R. 1988; Herpes simplex virus regulatory elements and the immunoglobulin octamer domain bind a common factor and are both targets for virion transactivation. Cell 52:435–445
     [Google Scholar]
  21. O’Hare P., Goding C. R., Haigh A. 1988; Direct combinatorial interaction between a herpes simplex virus regulatory protein and a cellular octamer-binding factor mediates specific induction of virus immediate-early gene expression. EMBO Journal 7:4231–4238
     [Google Scholar]
  22. Perng G. C., Chokephaibulkit K., Thompson R. L., Sawtell N. M., Slanina S. M., Ghiasi H., Nesburn A. B., Wechsler S. L. 1996; 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]
  23. Preston C. M. 1979; Control of herpes simplex virus type 1 mRNA synthesis in cells infected with wild-type virus or the temperature-sensitive mutant tsK. Journal of Virology 29:275–284
     [Google Scholar]
  24. Preston C. M., Mabbs R., Nicholl M. J. 1997; Construction and characterization of herpes simplex virus type 1 mutants with conditional defects in immediate early gene expression. Virology 229:228–239
     [Google Scholar]
  25. Purves F. C., Ogle W. O., Roizman B. 1993; Processing of the herpes simplex virus regulatory protein alpha 22 mediated by the UL13 protein kinase determines the accumulation of a subset of alpha and gamma mRNAs and proteins in infected cells. Proceedings of the National Academy of Sciences, USA 90:6701–6705
     [Google Scholar]
  26. Sacks W. R., Greene C. C., Aschman D. P., Schaffer P. A. 1985; Herpes simplex virus type 1 ICP27 is an essential regulatory protein. Journal of Virology 55:796–805
     [Google Scholar]
  27. Sawtell N. M. 1997; Comprehensive quantification of herpes simplex virus latency at the single-cell level. Journal of Virology 71:5423–5431
     [Google Scholar]
  28. Sawtell N. M. 1998; The probability of in vivo reactivation of herpes simplex virus type 1 increases with the number of latently infected neurons in the ganglia. Journal of Virology 72:6888–6892
     [Google Scholar]
  29. Sawtell N. M., Poon D. K., Tansky C. S., Thompson R. L. 1998; The latent herpes simplex virus type 1 genome copy number in individual neurons is virus strain specific and correlates with reactivation. Journal of Virology 72:5343–5350
     [Google Scholar]
  30. Sedarati F., Margolis T. P., Stevens J. G. 1993; Latent infection can be established with drastically restricted transcription and replication of the HSV-1 genome. Virology 192:687–691
     [Google Scholar]
  31. Slobedman B., Efstathiou S., Simmons A. 1994; Quantitative analysis of herpes simplex virus DNA and transcriptional activity in ganglia of mice latently infected with wild-type and thymidine kinase-deficient viral strains. Journal of General Virology 75:2469–2474
     [Google Scholar]
  32. Speck P. G., Simmons A. 1991; Divergent molecular pathways of productive and latent infection with a virulent strain of HSV-1. Journal of Virology 65:4001–4005
     [Google Scholar]
  33. Speck P. G., Simmons A. 1992; Synchronous appearance of antigen-positive and latently infected neurons in spinal ganglia of mice infected with a virulent strain of herpes simplex virus. Journal of General Virology 73:1281–1285
     [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 alpha gene mRNA is prominent in latently infected neurons. Science 235:1056–1059
     [Google Scholar]
  35. Stow N. D., Stow E. C. 1986; Isolation and characterization of a herpes simplex virus type 1 mutant containing a deletion within the gene encoding the immediate early polypeptide Vmw110. Journal of General Virology 67:2571–2585
     [Google Scholar]
  36. Stow N.D., Wilkie N.M. 1976; An improved technique for obtaining enhanced infectivity with herpes simplex virus type 1 DNA. Journal of General Virology 33:447–458
     [Google Scholar]
  37. Thompson R. L., Sawtell N. M. 1997; The herpes simplex virus type 1 latency-associated transcript gene regulates the establishment of latency. Journal of Virology 71:5432–5440
     [Google Scholar]
  38. Tullo A. B., Easty D. L., Hill T. J., Blyth W. A. 1982; Ocular herpes simplex and the establishment of latent infection. Transactions of the Opthalmological Societies of the United Kingdom 102:15–18
     [Google Scholar]
  39. Valyi Nagy T., Deshmane S., Dillner A., Fraser N. W. 1991; Induction of cellular transcription factors in trigeminal ganglia of mice by corneal scarification, herpes simplex virus type 1 infection, and explantation of trigeminal ganglia. Journal of Virology 65:4142–4152
     [Google Scholar]
  40. Wagner E. K., Bloom D. C. 1997; Experimental investigation of HSV latency. Clinical Microbiology Reviews 10:419–443
     [Google Scholar]
  41. Wagner E. K., Guzowski J. F., Singh J. 1995; Transcription of the HSV genome during productive and latent infection. Progress in Nucleic Acids Research and Molecular Biology 51:123–168
     [Google Scholar]
  42. Wilcox C. L., Smith R. L., Everett R. D., Mysofski D. 1997; The HSV-1 immediate early protein ICP0 is necessary for the efficient establishment of latent infection. Journal of Virology 71:6777–6785
     [Google Scholar]
  43. Wu N., Watkins S. C., Schaffer P. A., DeLuca N. A. 1996; Prolonged gene expression and cell survival after infection by a herpes simplex virus mutant defective in the immediate-early genes encoding ICP4, ICP27, and ICP22. Journal of Virology 70:6358–6369
     [Google Scholar]
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An analysis of herpes simplex virus gene expression during latency establishment and reactivation
J. Gen. Virol. 80, 1271 (1999); https://doi.org/10.1099/0022-1317-80-5-1271
/content/journal/jgv/10.1099/0022-1317-80-5-1271
/content/journal/jgv/10.1099/0022-1317-80-5-1271
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