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. 1985 Aug;55(2):322–328. doi: 10.1128/jvi.55.2.322-328.1985

Thymidine kinase-deficient herpes simplex virus type 2 genital infection in guinea pigs.

L R Stanberry, S Kit, M G Myers
PMCID: PMC254936  PMID: 2991558

Abstract

In guinea pigs, thymidine kinase-producing strains of herpes simplex virus type 2 replicated to high titer in the vagina and spinal cord, and animals developed severe clinical disease. Infection with thymidine kinase-deficient virus resulted in similar vaginal virus titers; however, animals exhibited little or no clinical illness and only low titers of virus were detected in spinal cord homogenate cultures. Neural and extraneural latent infection as well as recurrent infection were noted in animals inoculated with either thymidine kinase-producing or -deficient viruses. These data suggest that neural pathways are important in the pathogenesis of genital herpes and that virus-coded thymidine kinase may influence virulence but is not required for latency.

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Selected References

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  1. Anderson C. A., August M. J., Hsiung G. D. Pathogenicity of wild-type and temperature-sensitive mutants of herpes simplex virus type 2 in guinea pigs. Infect Immun. 1980 Oct;30(1):159–169. doi: 10.1128/iai.30.1.159-169.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aurelian L., Kessler I. I., Rosenshein N. B., Barbour G. Viruses and gynecologic cancers: herpesvirus protein (ICP 10/AG-4), a cervical tumor antigen that fulfills the criteria for a marker of carcinogenicity. Cancer. 1981 Jul 15;48(2 Suppl):455–471. doi: 10.1002/1097-0142(19810715)48:1+<455::aid-cncr2820481306>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  3. Baringer J. R., Swoveland P. Recovery of herpes-simplex virus from human trigeminal ganglions. N Engl J Med. 1973 Mar 29;288(13):648–650. doi: 10.1056/NEJM197303292881303. [DOI] [PubMed] [Google Scholar]
  4. Brandsma J., Miller G. Nucleic acid spot hybridization: rapid quantitative screening of lymphoid cell lines for Epstein-Barr viral DNA. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6851–6855. doi: 10.1073/pnas.77.11.6851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Crumpacker C. S., Schnipper L. E., Marlowe S. I., Kowalsky P. N., Hershey B. J., Levin M. J. Resistance to antiviral drugs of herpes simplex virus isolated from a patient treated with acyclovir. N Engl J Med. 1982 Feb 11;306(6):343–346. doi: 10.1056/NEJM198202113060606. [DOI] [PubMed] [Google Scholar]
  6. Donner L., Dubbs D. R., Kit S. Chromosomal site(s) of integration of Herpes simplex virus type 2 thymidine kinase gene in biochemically transformed human cells. Int J Cancer. 1977 Aug 15;20(2):256–267. doi: 10.1002/ijc.2910200214. [DOI] [PubMed] [Google Scholar]
  7. Field H. J., Bell S. E., Elion G. B., Nash A. A., Wildy P. Effect of acycloguanosine treatment of acute and latent herpes simplex infections in mice. Antimicrob Agents Chemother. 1979 Apr;15(4):554–561. doi: 10.1128/aac.15.4.554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Field H. J. Development of clinical resistance to acyclovir in herpes simplex virus-infected mice receiving oral therapy. Antimicrob Agents Chemother. 1982 May;21(5):744–752. doi: 10.1128/aac.21.5.744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Field H. J., Lay E. Characterization of latent infections in mice inoculated with herpes simplex virus which is clinically resistant to acyclovir. Antiviral Res. 1984 Apr;4(1-2):43–52. doi: 10.1016/0166-3542(84)90024-x. [DOI] [PubMed] [Google Scholar]
  10. Field H. J., Wildy P. The pathogenicity of thymidine kinase-deficient mutants of herpes simplex virus in mice. J Hyg (Lond) 1978 Oct;81(2):267–277. doi: 10.1017/s0022172400025109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gerdes J. C., Smith D. S. Recurrence phenotypes and establishment of latency following rabbit keratitis produced by multiple herpes simplex virus strains. J Gen Virol. 1983 Nov;64(Pt 11):2441–2454. doi: 10.1099/0022-1317-64-11-2441. [DOI] [PubMed] [Google Scholar]
  12. Gordon Y., Gilden D. H., Shtram Y., Asher Y., Tabor E., Wellish M., Devlin M., Snipper D., Hadar J., Becker Y. A low thymidine kinase-producing mutant of herpes simplex virus type 1 causes latent trigeminal ganglia infections in mice. Arch Virol. 1983;76(1):39–49. doi: 10.1007/BF01315702. [DOI] [PubMed] [Google Scholar]
  13. Hill T. J., Harbour D. A., Blyth W. A. Isolation of herpes simplex virus from the skin of clinically normal mice during latent infection. J Gen Virol. 1980 Mar;47(1):205–207. doi: 10.1099/0022-1317-47-1-205. [DOI] [PubMed] [Google Scholar]
  14. Jamieson A. T., Gentry G. A., Subak-Sharpe J. H. Induction of both thymidine and deoxycytidine kinase activity by herpes viruses. J Gen Virol. 1974 Sep;24(3):465–480. doi: 10.1099/0022-1317-24-3-465. [DOI] [PubMed] [Google Scholar]
  15. Kit S., Dubbs D. R. Regulation of herpesvirus thymidine kinase activity in LM(TK) cells transformed by ultraviolet light-irradiated herpes simplex virus. Virology. 1977 Jan;76(1):331–340. doi: 10.1016/0042-6822(77)90306-3. [DOI] [PubMed] [Google Scholar]
  16. Kit S., Kit M., Qavi H., Trkula D., Otsuka H. Nucleotide sequence of the herpes simplex virus type 2 (HSV-2) thymidine kinase gene and predicted amino acid sequence of thymidine kinase polypeptide and its comparison with the HSV-1 thymidine kinase gene. Biochim Biophys Acta. 1983 Nov 17;741(2):158–170. doi: 10.1016/0167-4781(83)90056-8. [DOI] [PubMed] [Google Scholar]
  17. Kit S., Qavi H. Thymidine kinase (TK) induction after infection of TK-deficient rabbit cell mutants with bovine herpesvirus type 1 (BHV-1): isolation of TK- BHV-1 mutants. Virology. 1983 Oct 30;130(2):381–389. doi: 10.1016/0042-6822(83)90092-2. [DOI] [PubMed] [Google Scholar]
  18. Kit S. Viral-associated and induced enzymes. Pharmacol Ther B. 1979;4(3):501–585. doi: 10.1016/0163-7258(79)90004-4. [DOI] [PubMed] [Google Scholar]
  19. Klein R. J., Friedman-Kien A. E., DeStefano E. Pathogenesis of experimental skin infections induced by drug-resistant herpes simplex virus mutants. Infect Immun. 1981 Dec;34(3):693–701. doi: 10.1128/iai.34.3.693-701.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Leung W. C., Dubbs D. R., Trkula D., Kit S. Mitochondrial and herpesvirus-specific deoxypyrimidine kinases. J Virol. 1975 Sep;16(3):486–497. doi: 10.1128/jvi.16.3.486-497.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. McDermott M. R., Smiley J. R., Leslie P., Brais J., Rudzroga H. E., Bienenstock J. Immunity in the female genital tract after intravaginal vaccination of mice with an attenuated strain of herpes simplex virus type 2. J Virol. 1984 Sep;51(3):747–753. doi: 10.1128/jvi.51.3.747-753.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. McLennan J. L., Darby G. Herpes simplex virus latency: the cellular location of virus in dorsal root ganglia and the fate of the infected cell following virus activation. J Gen Virol. 1980 Dec;51(Pt 2):233–243. doi: 10.1099/0022-1317-51-2-233. [DOI] [PubMed] [Google Scholar]
  23. Meignier B., Norrild B., Roizman B. Colonization of murine ganglia by a superinfecting strain of herpes simplex virus. Infect Immun. 1983 Aug;41(2):702–708. doi: 10.1128/iai.41.2.702-708.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Myers M. G., Stanberry L. R., Edmond B. J. Varicella-zoster virus infection of strain 2 guinea pigs. J Infect Dis. 1985 Jan;151(1):106–113. doi: 10.1093/infdis/151.1.106. [DOI] [PubMed] [Google Scholar]
  25. Nesburn A. B., Green M. T., Radnoti M., Walker B. Reliable in vivo model for latent herpes simplex virus reactivation with peripheral virus shedding. Infect Immun. 1977 Mar;15(3):772–775. doi: 10.1128/iai.15.3.772-775.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Overall J. C., Jr, Kern E. R., Schlitzer R. L., Friedman S. B., Glasgow L. A. Genital herpesvirus hominis infection in mice. I. Development of an experimental model. Infect Immun. 1975 Mar;11(3):476–480. doi: 10.1128/iai.11.3.476-480.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Price R. W., Khan A. Resistance of peripheral autonomic neurons to in vivo productive infection by herpes simplex virus mutants deficient in thymidine kinase activity. Infect Immun. 1981 Nov;34(2):571–580. doi: 10.1128/iai.34.2.571-580.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Richards J. T., Kern E. R., Overall J. C., Jr, Glasgow L. A. Differences in neurovirulence among isolates of Herpes simplex virus types 1 and 2 in mice using four routes of infection. J Infect Dis. 1981 Nov;144(5):464–471. doi: 10.1093/infdis/144.5.464. [DOI] [PubMed] [Google Scholar]
  29. Scriba M. Extraneural localisation of herpes simplex virus in latently infected guinea pigs. Nature. 1977 Jun 9;267(5611):529–531. doi: 10.1038/267529a0. [DOI] [PubMed] [Google Scholar]
  30. Scriba M. Herpes simplex virus infection in guinea pigs: an animal model for studying latent and recurrent herpes simplex virus infection. Infect Immun. 1975 Jul;12(1):162–165. doi: 10.1128/iai.12.1.162-165.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sibrack C. D., Gutman L. T., Wilfert C. M., McLaren C., St Clair M. H., Keller P. M., Barry D. W. Pathogenicity of acyclovir-resistant herpes simplex virus type 1 from an immunodeficient child. J Infect Dis. 1982 Nov;146(5):673–682. doi: 10.1093/infdis/146.5.673. [DOI] [PubMed] [Google Scholar]
  32. Stanberry L. R., Kern E. R., Richards J. T., Abbott T. M., Overall J. C., Jr Genital herpes in guinea pigs: pathogenesis of the primary infection and description of recurrent disease. J Infect Dis. 1982 Sep;146(3):397–404. doi: 10.1093/infdis/146.3.397. [DOI] [PubMed] [Google Scholar]
  33. Stevens J. G., Cook M. L., Jordan M. C. Reactivation of latent Herpes simplex virus after pneumococcal pneumonia in mice. Infect Immun. 1975 Apr;11(4):635–639. doi: 10.1128/iai.11.4.635-639.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Stevens J. G., Cook M. L. Latent herpes simplex virus in spinal ganglia of mice. Science. 1971 Aug 27;173(3999):843–845. doi: 10.1126/science.173.3999.843. [DOI] [PubMed] [Google Scholar]
  35. Straus S. E., Aulakh H. S., Ruyechan W. T., Hay J., Casey T. A., Vande Woude G. F., Owens J., Smith H. A. Structure of varicella-zoster virus DNA. J Virol. 1981 Nov;40(2):516–525. doi: 10.1128/jvi.40.2.516-525.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Tenser R. B., Jones J. C., Ressel S. J., Fralish F. A. Thymidine plaque autoradiography of thymidine kinase-positive and thymidine kinase-negative herpesviruses. J Clin Microbiol. 1983 Jan;17(1):122–127. doi: 10.1128/jcm.17.1.122-127.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Tenser R. B., Miller R. L., Rapp F. Trigeminal ganglion infection by thymidine kinase-negative mutants of herpes simplex virus. Science. 1979 Aug 31;205(4409):915–917. doi: 10.1126/science.224454. [DOI] [PubMed] [Google Scholar]
  38. Tenser R. B., Ressel S., Dunstan M. E. Herpes simplex virus thymidine kinase expression in trigeminal ganglion infection: correlation of enzyme activity with ganglion virus titer and evidence of in vivo complementation. Virology. 1981 Jul 15;112(1):328–341. doi: 10.1016/0042-6822(81)90638-3. [DOI] [PubMed] [Google Scholar]
  39. Walz M. A., Price R. W., Hayashi K., Katz B. J., Notkins A. L. Effect of immunization on acute and latent infections of vaginouterine tissue with herpes simplex virus types 1 and 2. J Infect Dis. 1977 May;135(5):744–752. doi: 10.1093/infdis/135.5.744. [DOI] [PubMed] [Google Scholar]
  40. Walz M. A., Price R. W., Notkins A. L. Latent ganglionic infection with herpes simplex virus types 1 and 2: viral reactivation in vivo after neurectomy. Science. 1974 Jun 14;184(4142):1185–1187. doi: 10.1126/science.184.4142.1185. [DOI] [PubMed] [Google Scholar]

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