1887

Abstract

Both famciclovir (FCV) and valaciclovir (VACV) are potent inhibitors of herpes simplex virus type 1 (HSV-1) in a murine cutaneous infection model. The object of the present study was to determine whether either drug had an effect on the anatomical distribution of infected neurons in the peripheral nervous system and to assess the consequences for infected cells during, immediately following and several months after a 9 day period of continuous treatment. Mice were inoculated via the neck with a recombinant strain of HSV-1 expressing the reporter gene under the immediate-early gene promoter. Sensory ganglia were sampled daily up to day 11 post-inoculation (p.i.) and infected cells were detected by means of the reporter gene product. Ganglia were also removed at 1·5 and 10 months p.i. and latency was assessed by explant co-cultivation and by using hybridization to detect LAT-expressing neurons. While both drugs reduced the severity of acute infection markedly, neither compound completely prevented the relentless distribution of infection among peripheral nervous tissue. Furthermore, there was a difference between the compounds regarding the expression of the reporter gene during and after termination of treatment and in the number of residual LAT-positive neurons.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-81-10-2385
2000-10-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/81/10/0812385a.html?itemId=/content/journal/jgv/10.1099/0022-1317-81-10-2385&mimeType=html&fmt=ahah

References

  1. 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]
  2. Bacon T. H., Standring-Cox R., Howard B. A. 1994; Comparative activity of penciclovir and acyclovir against herpes simplex virus type 2 in cell culture. Antiviral Research 23:25–36
    [Google Scholar]
  3. Boyd M. R., Bacon T. H., Sutton D., Cole M. 1987; Antiherpesvirus activity of 9-(4-hydroxy-3-hydroxy-methylbut-1-yl)guanine (BRL 39123) in cell culture. Antimicrobial Agents and Chemotherapy 31:1238–1242
    [Google Scholar]
  4. Earnshaw D. L., Bacon T. H., Darlison S. J., Edmonds K., Perkins R. M., Vere Hodge R. A. 1992; Mode of antiviral action of penciclovir in MRC-5 cells infected with herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus. Antimicrobial Agents and Chemotherapy 36:2747–2757
    [Google Scholar]
  5. Ecob-Prince M., Hassan K. 1994; Reactivation of latent herpes simplex virus from explanted dorsal root ganglia. Journal of General Virology 75:2017–2028
    [Google Scholar]
  6. 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 in 1814. Journal of General Virology 74:985–994
    [Google Scholar]
  7. Field H. J. 1996; Famciclovir – origins, progress and prospects. Expert Opinion on Investigational Drugs 5:925–938
    [Google Scholar]
  8. Field H. J., Thackray A. M. 1995; The effects of delayed-onset chemotherapy using famciclovir or valaciclovir in a murine immunosuppression model for HSV-1. Antiviral Chemistry & Chemotherapy 6:210–216
    [Google Scholar]
  9. Field H. J., Thackray A. M. 2000; Early therapy with valaciclovir or famciclovir reduces but does not abrogate herpes simplex virus neuronal latency. Nucleosides, Nucleotides and Nucleic Acids 19:461–470
    [Google Scholar]
  10. Field H. J., Tewari D., Sutton D., Thackray A. M. 1995; Comparison of efficacies of famciclovir and valaciclovir against herpes simplex virus type 1 in a murine immunosuppression model. Antimicrobial Agents and Chemotherapy 39:1114–1119
    [Google Scholar]
  11. Ilsley D. D., Lee S.-H., Miller W. H., Kuchta R. D. 1995; Acyclic guanosine analogs inhibit DNA polymerases alpha, delta, and epsilon with very different potencies and have unique mechanisms of action. Biochemistry 34:2504–2510
    [Google Scholar]
  12. 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]
  13. Lachmann R. H., Sadarangani M., Atkinson H. R., Efstathiou S. 1999; An analysis of herpes simplex virus gene expression during latency establishment and reactivation. Journal of General Virology 80:1271–1282
    [Google Scholar]
  14. 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]
  15. Shaw M. M., Watts P. A., Field H. J. 1999; Effects of ganciclovir, penciclovir and acyclovir on apoptosis. Antiviral Research 41:A66
    [Google Scholar]
  16. Simmons A., Slobedman B., Speck P., Arthur J., Efstathiou S. 1992; Two patterns of persistence of herpes simplex virus DNA sequences in the nervous systems of latently infected mice. Journal of General Virology 73:1287–1291
    [Google Scholar]
  17. Thackray A. M., Field H. J. 1996a; Differential effects of famciclovir and valaciclovir on the pathogenesis of herpes simplex virus in a murine infection model including reactivation from latency. Journal of Infectious Diseases 173:291–299
    [Google Scholar]
  18. Thackray A. M., Field H. J. 1996b; Comparison of effects of famciclovir and valaciclovir on pathogenesis of herpes simplex virus type 2 in a murine infection model. Antimicrobial Agents and Chemotherapy 40:846–851
    [Google Scholar]
  19. Thackray A. M., Field H. J. 1997; The influence of cyclosporin immunosuppression on the efficacy of famciclovir or valaciclovir chemotherapy studied in a murine herpes simplex virus type 1 infection model. Antiviral Chemistry & Chemotherapy 8:317–326
    [Google Scholar]
  20. Thackray A. M., Field H. J. 1998; Famciclovir and valaciclovir differ in the prevention of herpes simplex virus type 1 latency in mice: a quantitative study. Antimicrobial Agents and Chemotherapy 42:1555–1562
    [Google Scholar]
  21. Thackray A. M., Field H. J. 2000a; Persistence of infectious herpes simplex virus type 2 in the nervous system in mice after antiviral chemotherapy. Antimicrobial Agents and Chemotherapy 44:97–102
    [Google Scholar]
  22. Thackray A. M., Field H. J. 2000b; Further evidence from a murine infection model that famciclovir interferes with the establishment of HSV-1 latent infections. Journal of Antimicrobial Chemotherapy 45:825–833
    [Google Scholar]
  23. Thust R., Klöcking R., Voutilainen N., Wutzler P., Kaina B. 1998; Similarities and differences in the genotoxic and apoptosis-inducing capacity of ganciclovir and penciclovir, respectively, in HSVtk+ transfectants of Chinese hamster ovary cells. Antiviral Research 37:A81
    [Google Scholar]
  24. Vere Hodge R. A., Perkins R. M. 1989; Mode of action of 9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine (BRL 39123) against herpes simplex virus in MRC-5 cells. Antimicrobial Agents and Chemotherapy 33:223–229
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-81-10-2385
Loading
/content/journal/jgv/10.1099/0022-1317-81-10-2385
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