1887

Abstract

We have used a mouse model system and the comeal route of inoculation to examine the issue of extraneuronal persistence of herpes simplex vims type 1 (HSV-1). HSV-1 strain F DNA and inflammatory lesions were detected in corneal tissue of mice at 5, 11, 23, 37 and 60 days post-infection (p i.). Viral DNA was localized by PCR to epithelial cells and less frequently to cells in the stroma of the cornea. Viral proteins were not detected in the cornea and vims could not be isolated from tissue homogenates after 11 days p.i. even though histopathological lesions became progressively more severe at 37 and 60 days p.i. The DNA-containing cells were usually adjacent to the sites of inflammation or within these sites in the chronic stage (23, 37 and 60 days p.i.). In contrast to strain F, persistence of HSV-1 strain KOS DNA and inflammatory lesions were not detected after 11 days p.i.; this result suggests that the long-term persistence of HSV-1 DNA and the development of inflammatory lesions are vims strain-dependent. We tested for the possibility of transgenic HSV-1 immediate early gene (ICP4) promoter activity in chronically infected corneas of transgenic mice containing the ICP4 promoter fused to the bacterial -galactosidase coding sequence. Our results indicated that the chimeric transgene was expressed in the cornea at 5, 11, 23, 37 and 41 days p.i. Possible explanations for these results and mechanisms for the generation of the chronic inflammatory lesions are discussed. The properties of chronic HSV infections in the cornea may be similar to those which have been described for persistent or defective viral infections in other systems.

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1994-06-01
2022-05-26
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References

  1. Al-Saadi S. A., Gross P., Wildy P. 1988; Herpes simplex virus type 2 latency in the footpad of mice: effect of acycloguanosine on the recovery of virus. Journal of General Virology 69:433–438
    [Google Scholar]
  2. Banks T. A., Allen E. M., Dasgupta S., Sandri-Goldin R., Rouse B. T. 1991; Herpes simplex virus type 1 specific cytotoxic T lymphocytes recognize immediate early protein ICP27. Journal of Virology 65:3185–3191
    [Google Scholar]
  3. Cantin E. M., Chen J., McNeil J., Willey D. E., Openshaw H. 1991; Detection of herpes simplex virus DNA sequences in corneal transplant recipients by polymerase chain reaction assays. Current Eye Research 10:15–21
    [Google Scholar]
  4. Claoué C. M. P., Hodges T. J., Darville J. M., Hill T. J., Blyth W. A., Easty D. L. 1990; Possible latent infection with herpes simplex virus in the mouse eye. Journal of General Virology 71:2385–2390
    [Google Scholar]
  5. Clements G. B., Subak-Sharpe J. H. 1988; Herpes simplex virus type 2 establishes latency in the mouse footpad. Journal of General Virology 69:375–383
    [Google Scholar]
  6. Cook S. D., Hill J. M. 1991; Herpes simplex virus: molecular biology and the possibility of corneal latency. Survey of Ophthalmology 36:140–148
    [Google Scholar]
  7. Coupes D., Klapper P. E., Cleator G. M., Baily A. S., Tullo A. B. 1986; Herpesvirus simplex in chronic human stromal keratitis. Current Eye Research 5:735–738
    [Google Scholar]
  8. Crouse C. A., Pflugfelder S. C., Pereira I., Cleary T., Rabino-Witz S., Atherton S. S. 1990; Detection of herpes viral genomes in normal and diseased corneal epithelium. Current Eye Research 9:569–581
    [Google Scholar]
  9. Dawson C., Togni B., Moore T. E. 1968; Structural changes in chronic herpetic keratitis. Archives of Ophthalmology 79:740–747
    [Google Scholar]
  10. Deatley A. M., Spivack J. G., Lavi E., Fraser N. W. 1987; RNA from an immediate early region of the type 1 herpes simplex virus genome is present in the trigeminal ganglia of latently infected mice. Proceedings of the National Academy of Sciences U.S.A.: 843204–3208
    [Google Scholar]
  11. Doymaz M. Z., Rouse B. T. 1992; Immunopathology of herpes simplex virus infection. Current Topics in Microbiology and Immunology 179:121–136
    [Google Scholar]
  12. Fraser N. W., Block T. M., Spivack J. G. 1992; The latency associated transcripts of herpes simplex virus: RNA in search of a function. Virology 191:1–8
    [Google Scholar]
  13. Gressens P., Martin J. R. 1994; In situpolymerase chain reaction: localization of HSV-2 DNA sequences in infections of the nervous system. Journal of Virological Methods 46:61–83
    [Google Scholar]
  14. Gressens P., Langston C., Mitchell W. J., Martin J. R. 1993; Detection of viral DNA in neonatal herpes encephalitis autopsy tissues by solution-phase polymerase chain reaction: comparison with pathology and immunocytochemistry. Brain Pathology 3:237–250
    [Google Scholar]
  15. Hill T. J. 1985; Herpes simplex virus latency. In The Herpesviruses 3 pp 175–240 Roizman B. Edited by New York: Academic Press;
    [Google Scholar]
  16. Hill T. J., Harbour D. J., Blyth W. A. 1980; Isolation of herpes simplex virus from the skin of clinically normal mice during latent infection. Journal of General Virology 47:205–207
    [Google Scholar]
  17. McGeoch D. J., Dolan A., Donald S., Brauer D. H. K. 1986; Complete DNA sequence of the short repeat region in the genome of herpes simplex virus type 1. Nucleic Acids Research 14:1727–1745
    [Google Scholar]
  18. Mackem S., Roizman B. 1982; Differentiation between a promoter and regulator regions of herpes simplex virus 1: the functional domains and sequence of a movable a regulator. Proceedings of the National Academy of Sciences U.S.A.: 794917–1921
    [Google Scholar]
  19. McKnight S. L. 1980; The nucleotide sequence and transcript map of the herpes simplex virus thymidine kinase gene. Nucleic Acids Research 8:5949–5964
    [Google Scholar]
  20. Martin S., Zhu X., Silverstein S. J., Courtney R. J., Yao F., Jenkins F. J., Rouse B. T. 1990; Murine cytotoxic T lymphocytes specific for herpes simplex virus type 1 recognize the immediate early protein ICP4 but not 1CP0. Journal of General Virology 71:2391–2399
    [Google Scholar]
  21. Mercadal C. M., Bouley D. M., DeStephano D., Rouse B. T. 1993; Flerpetic stromal keratitis in the reconstituted SCID mouse model. Journal of Virology 67:3404–3408
    [Google Scholar]
  22. Mercer E. H., Hoyle G. W., Kapur R. P., Brinster R. L., Palmiter R. D. 1991; The dopamine β-hydroxylase gene promoter directs expression of E. coli lacZto sympathetic and other neurons in adult transgenic mice. Neuron 7:703–716
    [Google Scholar]
  23. Metcalf J. F., Hamilton D. S., Reichert R. W. 1979; Herpetic keratitis in athymic (nude) mice. Infection and Immunity 26:1164–1171
    [Google Scholar]
  24. Mitchell W. J., Martin J. R. 1992; Herpes simplex virus type 1 replicates in the lens and induces cataracts in mice. Laboratory Investigation 66:32–38
    [Google Scholar]
  25. Mitchell W. J., Deshmane S. L., Dolan A., McGeoch D. J., Fraser N. W. 1990a; Characterization of herpes simplex virus type 2 transcription during latent infection of mouse trigeminal ganglia. Journal of Virology 64:5342–5348
    [Google Scholar]
  26. Mitchell W. J., Lirette R. P., Fraser N. W. 1990b; 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]
  27. Mitchell W. J., DeSanto R. J., Zhang S., Odenwald W. F., Arnheiter H. 1993; Herpes simplex virus pathogenesis in transgenic mice is altered by the homeodomain protein Hox 1.3. Journal of Virology 67:4484–4491
    [Google Scholar]
  28. Newell C. K., Martin S., Sendele D., Mercadal C. M., Rouse B. T. 1989; Herpes simplex virus-induced stroma) keratitis: role of T-lymphocyte subsets in immunopathology. Journal of Virology 63:769–775
    [Google Scholar]
  29. Oakes J. E., Monteiro C. A., Cubitt C. L., Lausch R. N. 1993; Induction of interleukin 8 gene expression is associated with herpes simplex virus infection of human corneal keratocytes but not human corneal epithelial cells. Journal of Virology 67:4777–4784
    [Google Scholar]
  30. Pacha R. F., Meiss R. J., Condit R. C. 1990; Structure and expression of the vaccinia virus gene which prevents virus-induced breakdown of RNA. Journal of Virology 64:3853–3863
    [Google Scholar]
  31. Roizman B., Sears A. E. 1990; Herpes simplex viruses and their replication. In Virology, 2nd edn.. pp 1795–1841 Fields B. N., Knipe D. M. Edited by New York: Raven Press;
    [Google Scholar]
  32. Sabbaga E. M., Pavan-Langston D. P., Bean K. M., Dunkel E. C. 1988; Detection of HSV nucleic acid sequences in the cornea during acute and latent ocular disease. Experimental Eye Research 47:545–553
    [Google Scholar]
  33. Sanes J. R., Rubenstein J. L., Nicolas J. F. 1986; Use of a recombinant retrovirus to study post-implantation cell lineage in mouse embryos. EMBO Journal 5:3133–3142
    [Google Scholar]
  34. Scriba M. 1977; Extraneural localization of herpes simplex virus in latently infected guinea pigs. Nature; London: 267529–531
    [Google Scholar]
  35. 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]
  36. Stanton L. W., Fahlander P. D., Tesser P. M., Marcu K. B. 1984; Nucleotide sequence comparison of normal and translocated murine c-mycgenes. Nature; London: 310423–125
    [Google Scholar]
  37. Stevens J. G. 1975; Latent herpes simplex virus and the nervous system. Current Topics in Microbiology and Immunology 70:31–50
    [Google Scholar]
  38. Stevens J. G. 1989; Human herpesviruses: a consideration of the latent state. Microbiological Reviews 53:318–332
    [Google Scholar]
  39. 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]
  40. Triezenberg S. J., LaMarco K. L., McKnight S. L. 1988; Evidence of DNA: protein interactions that mediate HSV-1 immediate early gene activation by VP16. Genes and Development 2:730–742
    [Google Scholar]
  41. Tullo A. B., Shimeld C., Blyth W. A., Hill T. J., Easty D. L. 1982; Spread of virus and distribution of latent infection following ocular herpes simplex in the non-immune and immune mouse. Journal of General Virology 63:95–101
    [Google Scholar]
  42. Valyi-Nagy T., Deshmane S. L., Raengsakulrach B., Nicosia M., Gesser R. M., Wysocka M., Dillner A., Fraser N. W. 1992; Herpes simplex virus type 1 mutant strain in 1814 establishes a unique slowly progressing infection in SCID mice. Journal of Virology 66:7336–7345
    [Google Scholar]
  43. Wagner E. K., Devi-Rao G., Feldman L. T., Dobson A. T., Zhang Y., Flanagan W. M., Stevens J. G. 1988; Physical characterization of the herpes simplex virus latency-associated transcript in neurons. Journal of Virology 62:1194–1202
    [Google Scholar]
  44. Wander A. H., Centifanto Y. M., Kaufman H. E. 1980; Strain specificity of clinical isolates of herpes simplex virus. Archives of Ophthalmology 98:458–1461
    [Google Scholar]
  45. Wechsler S. L., Nesburn A. B., Watson R., Slanina S. M., Ghiasi H. 1988; Fine mapping of the latency-related gene of herpes simplex virus type 1: alternative splicing produces distinct latency- related RNAs containing open reading frames. Journal of Virology 62:4051–1058
    [Google Scholar]
  46. Whitley R. J. 1985; Epidemiology of herpes simplex viruses. In The Herpesviruses 3 pp 1–44 Roizman B. Edited by New York: Academic Press;
    [Google Scholar]
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