1887

Abstract

Laboratory animal models are important tools for the identification of avirulent herpes simplex virus type 1 (HSV-1) strains which have potential for use in humans as vaccine strains or gene therapy vectors. We have studied an HSV-1 17 variant, 1716, that has a deletion in the γ34.5 gene and which replicates poorly in the footpads of mice and is unable to grow in the mouse central nervous system or dorsal root ganglia (DRG) of the peripheral nervous system following peripheral inoculation. However, 1716 is known to be capable of establishing latent infections in the DRG of mice. Here we show that 1716 is avirulent after ocular infection and has low virulence after intracranial inoculation in SCID mice. Since SCID mice are much more sensitive to HSV-1 infection than immunocompetent mice, our results clearly demonstrate the drastically reduced virulence of the variant 1716 and provide additional support for the hypothesis that this variant would be avirulent in humans.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-75-8-2059
1994-08-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/75/8/JV0750082059.html?itemId=/content/journal/jgv/10.1099/0022-1317-75-8-2059&mimeType=html&fmt=ahah

References

  1. Bohenzky R. A., Parpavassiliou A. G., Gelman I. H., Silverstein S. 1993; Identification of a promoter mapping within the reiterated sequences that flank the herpes simplex virus type 1 UL region. Journal of Virology 67:632–642
    [Google Scholar]
  2. Bosma G. C., Custer R. P., Bosma M. J. 1983; A severe combined immunodeficiency mutation in the mouse. Nature; London: 301527–530
    [Google Scholar]
  3. Chou J., Roizman B. 1992; The γ134.5 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, U.S.A 89:3266–3270
    [Google Scholar]
  4. Chou J., Kern E. R., Whitley R. J., Roizman B. 1990; Mapping of herpes simplex virus neurovirulenceto γ134.5, a gene nonessential for growth in culture. Science 250:1262–1266
    [Google Scholar]
  5. Coen D. M., Kosz-Vnenchak M., Jacobson J. G., Leib D. A., Bogard C. L., Schaffer P. A., Tyler K. L., Knipe D. M. 1989; Thymidine kinase-negative herpes simplex virus mutants establish latency in mouse trigeminal ganglia but do not reactivate. Proceedings of the National Academy of Sciences, U.S.A 86:4736–4740
    [Google Scholar]
  6. Deatly A. M., Spivack J. G., Lavi E., O’Boyle D. R.II Fraser N. W. 1988; Latent herpes simplex virus type 1 transcripts in peripheral and central nervous system tissues of mice map to similar regions of the viral genome. Journal of Virology 62:749–756
    [Google Scholar]
  7. Fraser N. W., Valyi-Nagy T. 1993; Viral, neuronal and immune factors which may influence herpes simplex virus (HSV) latency and reactivation. Microbial Pathogenesis 15:83–91
    [Google Scholar]
  8. Gesser R. M., Valyi-Nagy T., Fraser N. W. 1994; Restricted herpes simplex virus type 1 gene expression within sensory neurons in the absence of functional B and T lymphocytes. Virology 200:791–795
    [Google Scholar]
  9. Maclean A. R., Fareed M. U., Robertson L., Harland J., Brown S. M. 1991; Herpes simplex virus type 1 deletion variants 1714 and 1716 pinpoint neurovirulence-related sequences in Glasgow strain 17+between immediate early gene 1 and the ‘a’ sequence. Journal of General Virology 72:631–639
    [Google Scholar]
  10. Minagawa H., Sakuma S., Mohri S., Watambe T. 1988; Herpes simplex virus type 1 infection in mice with severe combined immunodeficiency (SCID). Archives of Virology 103:73–82
    [Google Scholar]
  11. Robertson L. M., Maclean A. R., Brown S. M. 1992; Peripheral replication and latency reactivation kinetics of the nonneurovirulent herpes simplex virus type 1 variant 1716. Journal of General Virology 73:967–970
    [Google Scholar]
  12. Taha M. Y., Brown S. M., Clements G. B., Graham D. I. 1990; The JH2604 deletion variant of herpes simplex virus type 2 (HG52) fails to produce necrotizing encephalitis following intracranial inoculation of mice. Journal of General Virology 71:1597–1601
    [Google Scholar]
  13. Valyi-Nagy T., Deshmane S. L., Spivack J. G., Steiner I., Ace C. I., Preston C. M., Fraser N. W. 1991a; Investigation of herpes simplex virus type 1 (HSV-1) gene expression and DNA synthesis during the establishment of latent infection by an HSV-1 variant, in1814, that does not replicate in mouse trigeminal ganglia. Journal of General Virology 72:641–649
    [Google Scholar]
  14. Valyi-Nagy T., Deshmane S. L., Dillner A. J., Fraser N. W. 1991b; Induction of cellular transcription factors in trigeminal ganglia of mice by corneal scarification, herpes simplex virus 1 type infection and explantation of trigeminal ganglia. Journal of Virology 65:4142–4152
    [Google Scholar]
  15. 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 in1814 establishes a unique, slowly progressing infection in SCID mice. Journal of Virology 66:7336–7345
    [Google Scholar]
  16. Valyi-Nagy T., Gesser R. M., Raengsakulrach B., Deshmane S. L., Randazzo B. P., Dillner A. J., Fraser N. W. 1994; A thymidine kinase-negative HSV-1 strain establishes a persistent infection in SCID mice that features uncontrolled peripheral replication but only marginal nervous system involvement. Virology 199:484–490
    [Google Scholar]
  17. Whitley R. J., Kern E. R., Chatterjee S., Chou J., Roizman B. 1993; Replication, establishment of latency, and induced reactivation of herpes simplex virus gamma 1 34.5 deletion mutants in rodent models. Journal of Clinical Investigation 91:2837–2843
    [Google Scholar]
  18. Yeh L., Schaffer P. A. 1993; A novel class of transcripts expressed with late kinetics in the absence of ICP4 spans the junction between the long and short segments of the herpes simplex virus type 1 genome. Journal of Virology 67:7373–7382
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-75-8-2059
Loading
/content/journal/jgv/10.1099/0022-1317-75-8-2059
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