1887

Abstract

Herpes simplex virus type 1 (HSV-1) establishes latent infection in the sensory ganglia. To investigate the process of reactivation from latency, we used the RNA polymerase chain reaction (RNA-PCR) to detect the expression of several HSV genes. BALB/c mice were inoculated in the anterior ocular chamber with HSV-1 strain KOS and the trigeminal ganglia were examined at least 8 weeks after inoculation. Latency-associated transcripts (LATs) were found in the latently infected ganglia and remained detectable 120 h after explantation. Besides LATs, we detected transcripts for infected cell protein 0 (ICPO) (Vmw110) 24 h after explantation, but RNAs encoding ICP4 (Vmw175), ICP27, thymidine kinase and VP16 (ICP25; Vmw65) remained undetectable for 120 h after explantation. Following reactivation of HSV-1 by administration of cyclophosphamide and dexamethasone, all viral transcripts including ICPO RNA became detectable. The RNA-PCR enabled us to detect ICPO RNA much earlier than has been previously reported in studies using the Northern blot technique and has laid a foundation for further study of viral and cellular transcripts during reactivation. Our results suggest that the process of reactivation of HSV-1 from trigeminal ganglia may be divided into at least two steps: (i) initiation of ICPO gene transcription and (ii) detectable transcription of the other genes. The second step may be regulated in part by the host immune system, since cyclophosphamide and dexamethasone administration enabled the detection of several viral transcripts.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-75-3-647
1994-03-01
2024-04-16
Loading full text...

Full text loading...

/deliver/fulltext/jgv/75/3/JV0750030647.html?itemId=/content/journal/jgv/10.1099/0022-1317-75-3-647&mimeType=html&fmt=ahah

References

  1. Chomczynski P., Sacchi N. 1987; Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Analytical Biochemistry 162:156–159
    [Google Scholar]
  2. Ecob-Prince M. S., Rixon F. J., Preston C. M., Hassan K., Kennedy P. G. E. 1993; 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]
  3. Elshiekh N. A., Harris-Hamilton E., Bachenheimer S. L. 1991; Differential dependence of herpes simplex virus immediate-early gene expression on de novo-infected cell protein synthesis. Journal of Virology 65:6430–6437
    [Google Scholar]
  4. 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]
  5. Gordon Y. J., McKnight J. L., Ostrove J. M., Romanowski E., Araullo-Cruz T. 1990; Host species and strain differences affect the ability of an HSV-1 ICPO deletion mutant to establish latency and spontaneously reactivate in vivo. Virology 178:469–177
    [Google Scholar]
  6. 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]
  7. Hino M., Sekizawa T., Openshaw H. 1988; Ricin injection eliminates latent herpes simplex virus in the mouse. Journal of Infectious Diseases 157:1270–1271
    [Google Scholar]
  8. 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.: 867596–7600
    [Google Scholar]
  9. 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]
  10. Liu Y., Sakai Y., Minagawa H., Toh Y., Ishibashi T., Inomata H., Mori R. 1993; Induction of bilateral retinal necrosis in mice by unilateral intracameral inoculation of a glycoprotein-C deficient clinical isolate of herpes simplex virus type 1. Archives of Virology 129:105–118
    [Google Scholar]
  11. Lynas C., Cook S. D., Laycock K. A., Bradfield J. W. B., Maitland N. J. 1989a; Detection of latent virus mRNA in tissues using the polymerase chain reaction. Journal of Pathologv 157:285–289
    [Google Scholar]
  12. Lynas C., Laycock K. A., Cook S. D., Hill T. J., Blyth W. A., Maitland N. J. 1989b; Detection of herpes simplex virus type 1 gene expression in latently and productively infected mouse ganglia using the polymerase chain reaction. Journal of General Virology 70:2345–2355
    [Google Scholar]
  13. McGeoch D. J., Dalrymple M. A., Davison A. J., Dolan A., Frame M. C., McNab D., Perry L. J., Scott J. E., Taylor P. 1988; The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. Journal of General Virology 69:1531–1574
    [Google Scholar]
  14. Nash A. A., Löhr J. M. 1992; Pathogenesis and immunology of herpesvirus infections of the nervous system. In Neuropathogenic Viruses and Immunity pp 155–175 Specter S., Bendinelli M., Friedman H. Edited by New York & London: Plenum Press;
    [Google Scholar]
  15. 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]
  16. Rixon F. J., Clements J. B. 1982; Detailed structural analysis of two spliced HSV-1 immediate-early mRNAs. Nucleic Acids Research 10:2241–2256
    [Google Scholar]
  17. 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]
  18. 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]
  19. Roizman B., Sears A. E. 1987; An inquiry into the mechanisms of herpes simplex virus latency. Annual Review of Microbiology 41:543–571
    [Google Scholar]
  20. Sacks W. R., Schaffer P. A. 1987; Deletion mutants in the gene encoding the herpes simplex virus type 1 immediate-early protein ICPO exhibit impaired growth in cell culture. Journal of Virology 61:829–839
    [Google Scholar]
  21. Schochetman G., Ou C. Y., Jones W. K. 1988; Polymerase chain reaction. Journal of Infectious Diseases 158:1154–1157
    [Google Scholar]
  22. Sedarati F., Izumi K. M., Wagner E. K., Stevens J. G. 1989; Herpes simplex virus type 1 latency-associated transcription plays no role in establishment or maintenance of a latent infection in murine sensory neurons. Journal of Virology 63:4455–1458
    [Google Scholar]
  23. Shimeld C., Hill T. J., Blyth W. A., Easty D. L. 1990; Reactivation of latent infection and induction of recurrent herpetic eye disease in mice. Journal of General Virology 71:397–404
    [Google Scholar]
  24. Shull M. M., Ormsby I., Pawlowski S., Diebold R. J., Yin M., Allen R., Sidman C., Proetzel G., Calvin D., Annunziata N., Doetschman T. 1992; Targeted disruption of the mouse transforming growth factor-/ll gene results in multifocal inflammatory disease. Nature 359:693–699
    [Google Scholar]
  25. Simmons A., Tscharke D. C. 1992; Anti-CD8 impairs clearance of herpes simplex virus from the nervous system: implications for the fate of virally infected neurons. Journal of Experimental Medicine 175:1337–1344
    [Google Scholar]
  26. 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]
  27. Spivack J. G., Fraser N. W. 1988; Expression of herpes simplex virus type 1 latency-associated transcripts in the trigeminal ganglia of mice during acute infection and reactivation of latent infection. Journal of Virology 62:1479–1485
    [Google Scholar]
  28. 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 20-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]
  29. Sprecher E., Becker Y. 1992; Detection of IL-1β, TNF-α, and IL-6 gene transcription by the polymerase chain reaction in keratino-cytes, Langerhans cells and peritoneal exudate cells during infection with herpes simplex virus-1. Archives of Virology 126:253–269
    [Google Scholar]
  30. Stanberry L. R. 1986; Herpesvirus latency and recurrence. Progress in Medical Virology 33:61–77
    [Google Scholar]
  31. Stevens J. G. 1989; Human herpesviruses: a consideration of the latent state. Microbiological Reviews 53:318–332
    [Google Scholar]
  32. Stevens J. G., Wagner E. K., Devi-Rao G. B., Cook M. L., Feldman L. T. 1987; RNA complementary to a herpesvirus gene mRNA is prominent in latently infected neurons. Science 235:1056–1059
    [Google Scholar]
  33. 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 transcript variant in a rabbit eye model. Journal of Virology 65:6989–6993
    [Google Scholar]
  34. 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]
  35. Wagner E. K. 1990; Herpesvirus transcription -general aspects. In Herpesvirus Transcription and Its Regulation pp 1–15 Wagner E. K. Edited by Boca Raton: CRC Press;
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-75-3-647
Loading
/content/journal/jgv/10.1099/0022-1317-75-3-647
Loading

Data & Media loading...

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