Skip to main content
SpringerLink
Log in

Experimental skin infection with an Acyclovir resistant herpes simplex virus mutant: Response to antiviral treatment and protection against reinfection

  • Original Papers
  • Published:
Archives of Virology Aims and scope Submit manuscript

Summary

Skin infections induced in hairless mice with an Acyclovir resistant herpes simplex virus (HSV) mutant were not followed by the death of the animals, and the survivors had no evidence of latent infections in their sensory ganglia. However, mutant virus was detected in the ganglia during the acute phase of the infection. Mice inoculated with the mutant were fully protected against the fatal outcome of the infection when subsequently challenged with the relatively pathogenic parental virus. In addition the frequency of latent infections established after challenge was significantly reduced. Phosphonoacetic acid treatment of the primary mutant-induced infection abolished the protection against reinfection with parental virus. Acyclovir treatment of the primary infection with the mutant virus did not affect the protection against reinfection with parental virus. The results indicate that drug-resistant, latency-negative, HSV mutants are a promising starting point for the development of an attenuated HSV vaccine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Aswell, J. F., Allen, G. P., Jamieson, A. T., Campbell, D. E., Gentry, G. A.: Antiviral Activity of Arabinosylthymine in herpesviral replication: mechanism of actionin vivo andin vitro. Antimicrob. Agents Chemother.12, 243–254 (1977).

    Google Scholar 

  2. Brown, S. M., Subak-Sharpe, J. H., Warren, K. G., Wroblewska, Z., Koprowski, H.: Detection by complementation of defective or uninducible (herpes simplex type 1) virus genomes latent in human ganglia. Proc. Natl. Acad. Sci. U.S.A.76, 2364–2368 (1979).

    Google Scholar 

  3. Chen, M. S., Prusoff, W. H.: Phosphorylation of 5-iodo-5′-amino-2′5′, dideoxyuridine by herpes simplex virus type 1 encoded thymidine kinase. J. biol. Chem.254, 10,449–10,452 (1979).

    Google Scholar 

  4. Elion, G. B., Furman, P. A., Fyfe, J. A., de Miranda, P., Beauchamp, L., Schaeffer, H. J.: Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl)guanine. Proc. Natl. Acad. Sci. U.S.A.74, 5716–5720 (1977).

    Google Scholar 

  5. Field, H. J., Wildy, P.: The pathogenicity of thymidine kinase-deficient mutants of herpes simplex virus in mice. J. Hyg., Camb.81, 267–277 (1978).

    Google Scholar 

  6. Fyfe, J. A., Keller, P. M., Furman, P. A., Miller, R. L., Elion, G. B.: Thymidine kinase from herpes simplex virus phosphorylates the new antiviral compound, 9-(2-hydroxyethoxymethyl)guanine. J. biol. Chem.253, 8721–8727 (1978).

    Google Scholar 

  7. Gerdes, J. C., Marsden, H. S., Cook, M. L., Stevens, J. G.: Acute infection of differentiated neuroblastoma cells by latency-positive and latency-negative herpes simplex virusts mutants. Virology94, 430–441 (1979).

    Google Scholar 

  8. Kitches, E. N., Morahan, P. S., Tew, J. G., Murray, B. K.: Protection from oral herpes simplex virus infection by a nucleic acid-free virus vaccine. Infect. Immun.16, 955–960 (1977).

    Google Scholar 

  9. Klein, R. J.: Isolation of herpes simplex virus clones and drug resistant mutants by microcultures. Arch. Virol.49, 73–80 (1975).

    Google Scholar 

  10. Klein, R. J., Friedman-Kien, A. E.: Phosphonoacetic acid-resistant herpes simplex virus infection in hairless mice. Antimicrob. Agents Chemother.7, 289 to 293 (1975).

    Google Scholar 

  11. Klein, R. J., Friedman-Kien, A. E., Brady, E.: Latent herpes simplex virus in ganglia of mice after primary infection and reinoculation at a distant site. Arch. Virol.57, 161–166 (1978).

    Google Scholar 

  12. Klein, R. J., Friedman-Kien, A. E., De Stefano, E.: Latent herpes simplex virus infections in sensory ganglia of hairless mice prevented by acycloguanosine. Antimicrob. Agents Chemother.15, 723–729 (1979).

    Google Scholar 

  13. Klein, R. J., Friedman-Kien, A. E., Fondak, A. A., Buimovici-Klein, E.: Immune response and latent infection after topical treatment of herpes simplex virus infection in hairless mice. Infect. Immun.16, 842–848 (1977).

    Google Scholar 

  14. Klein, R. J., Friedman-Kien, A. E., Yellin, P. B.: Orofacial herpes simplex virus infection in hairless mice: latent virus in trigeminal ganglia after topical antiviral treatment. Infect. Immun.20, 130–135 (1978).

    Google Scholar 

  15. Lofgren, K. W., Stevens, J. G., Marsden, H. S., Subak-Sharpe, J. H.: Temperature-sensitive mutants of herpes simplex virus differ in the capacity to establish latent infections in mice. Virology76, 440–443 (1977).

    Google Scholar 

  16. McKendall, R. R., Klassen, T., Beringer, J. R.: Host defenses in herpes simplex infections of the nervous system: effect of antibody on disease and viral spread. Infect. Immun.23, 305–311 (1979).

    Google Scholar 

  17. Openshaw, H., Shavrina Asher, L. V., Wohlenberg, C., Sekizawa, T., Notkins, A. L.: Acute and latent infection in sensory ganglia with herpes simplex virus: immune control and virus reactivation. J. gen. Virol.44, 205–215 (1979).

    Google Scholar 

  18. Price, R. W., Schmitz, J.: Route of infection, systemic host resistance, and integrity of ganglionic axons influence acute and latent herpes simplex virus infection of the superior cervical ganglion. Infect. Immun.23, 373–383 (1979).

    Google Scholar 

  19. Price, R. W., Walz, M. A., Wohlenberg, C., Notkins, A. L.: Latent infection of sensory ganglia with herpes simplex virus: efficacy of immunization. Science188, 938–940 (1975).

    Google Scholar 

  20. Tenser, R. B., Dunstan, M. E.: Herpes simplex virus thymidine kinase expression in infection of the trigeminal ganglion. Virology99, 417–422 (1979).

    Google Scholar 

  21. Tenser, R. B., Miller, R. L., Rapp, F.: Trigeminal ganglion infection by thymidine kinase-negative mutants of herpes simplex virus. Science205, 915–917 (1979).

    Google Scholar 

  22. Yamamoto, H., Walz, A., Notkins, A. L.: Viral-specific thymidine kinase in sensory ganglia of mice infected with herpes simplex virus. Virology76, 866–869 (1977).

    Google Scholar 

  23. Zygraich, N., Huygelen, C.:In vivo behaviour of a temperature sensitive(ts) mutant of herpesvirus hominis type 2. Arch. ges. Virusforsch.43, 103–111 (1973).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Microbiology and Dermatology, New York University School of Medicine, New York, USA

    R. J. Klein, E. DeStefano, E. Brady & A. E. Friedman-Kien

Authors
  1. R. J. Klein
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. DeStefano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Brady
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. E. Friedman-Kien
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

With 1 Figure

This is publication No. 44 from the Cooperative Antiviral Testing Group of the Antiviral Substances Program, Development and Applications Branch, National Institute of Allergy and Infectious Diseases, Bethesda, MD, U.S.A.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Klein, R.J., DeStefano, E., Brady, E. et al. Experimental skin infection with an Acyclovir resistant herpes simplex virus mutant: Response to antiviral treatment and protection against reinfection. Archives of Virology 65, 237–246 (1980). https://doi.org/10.1007/BF01314540

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01314540

Keywords

Search

Navigation