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. 1977 Apr;11(4):701–707. doi: 10.1128/aac.11.4.701

Chemotherapy of Genital Herpes Simplex Virus Type 2 Infections of Female Hamsters

Harold E Renis 1
PMCID: PMC352054  PMID: 856023

Abstract

The antiviral activity of 1-β-d-arabinofuranosylcytosine (ara-C, cytarabine, Cytosar), 5-iodo-2′-deoxyuridine (IdUrd), 9-β-d-arabinofuranosyladenine (ara-A), and disodium phosphonoacetate (PAA) have been compared in herpes simplex virus type 2 (HSV-2)-infected primary rabbit kidney cells and in female hamsters with genital HSV-2 infection. In vitro, ara-C and IdUrd were more active than ara-A, and PAA was least active. In female hamsters with genital HSV-2 infection, intravaginal treatment with PAA or ara-A was more effective than either ara-C or IdUrd. PAA was more active than ara-A when treatment was initiated early (1 h) after infection. The activity of PAA was greatly reduced if initiation of treatment was delayed for 24 h. Both PAA and ara-A reduced the virus titers of the vagina and protected hamsters from death when the drugs were given by either the intravaginal or subcutaneous route, with intravaginal treatment being more effective.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aronson M. D., Phillips C. F., Gump D. W., Albertini R. J., Phillips C. A. Vidarabine therapy for severe herpesvirus infections. An unusual syndrome of chronic varicella and transient immunologic deficiency. JAMA. 1976 Mar 29;235(13):1339–1342. doi: 10.1001/jama.235.13.1339. [DOI] [PubMed] [Google Scholar]
  2. Aurelian L. Virions and antigens of herpes virus type 2 in cervical carcinoma. Cancer Res. 1973 Jun;33(6):1539–1547. [PubMed] [Google Scholar]
  3. Duff R., Rapp F. Properties of hamster embryo fibroblasts transformed in vitro after exposure to ultraviolet-irradiated herpes simplex virus type 2. J Virol. 1971 Oct;8(4):469–477. doi: 10.1128/jvi.8.4.469-477.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fiala M., Chow A. W., Miyasaki K., Guze L. B. Susceptibility of herpesviruses to three nucleoside analogues and their combinations and enhancement of the antiviral effect of acid pH. J Infect Dis. 1974 Jan;129(1):82–85. doi: 10.1093/infdis/129.1.82. [DOI] [PubMed] [Google Scholar]
  5. Gerstein D. D., Dawson C. R., O J. O. Phosphonoacetic acid in the treatment of experimental herpes simplex keratitis. Antimicrob Agents Chemother. 1975 Mar;7(3):285–288. doi: 10.1128/aac.7.3.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goodman E. L., Luby J. P., Johnson M. T. Prospective double-blind evaluation of topical adenine arabinoside in male herpes progenitalis. Antimicrob Agents Chemother. 1975 Dec;8(6):693–697. doi: 10.1128/aac.8.6.693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hutfield D. C. Herpes genitalis. Br J Vener Dis. 1968 Sep;44(3):241–250. doi: 10.1136/sti.44.3.241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hyndiuk R. A., Kaufman H. E. Newer compounds in therapy of herpes simplex keratitis. Arch Ophthalmol. 1967 Nov;78(5):600–605. doi: 10.1001/archopht.1967.00980030602008. [DOI] [PubMed] [Google Scholar]
  9. Johnson M. T., Buchanan R. A., Luby J. P., Mikulec D. Treatment of varicella-zoster virus infections with adenine arabinoside. J Infect Dis. 1975 Mar;131(3):225–229. doi: 10.1093/infdis/131.3.225. [DOI] [PubMed] [Google Scholar]
  10. KAUFMAN H. E., CAPELLA J. A., MALONEY E. D., ROBBINS J. E., COOPER G. M., UOTILA M. H. CORNEAL TOXICITY OF CYTOSINE ARABINOSIDE. Arch Ophthalmol. 1964 Oct;72:535–540. doi: 10.1001/archopht.1964.00970020535019. [DOI] [PubMed] [Google Scholar]
  11. KAUFMAN H. E. Clinical cure of herpes simplex keratitis by 5-iodo-2-deoxyuridine. Proc Soc Exp Biol Med. 1962 Feb;109:251–252. doi: 10.3181/00379727-109-27169. [DOI] [PubMed] [Google Scholar]
  12. KAUFMAN H. E., MALONEY E. D. IDU and cytosine arabinoside in experimental herpetic keratitis. Arch Ophthalmol. 1963 May;69:626–629. doi: 10.1001/archopht.1963.00960040632017. [DOI] [PubMed] [Google Scholar]
  13. KAUFMAN H., MARTOLA E. L., DOHLMAN C. Use of 5-iodo-2'-deoxyuridine (IDU) in treatment of herpes simplex keratitis. Arch Ophthalmol. 1962 Aug;68:235–239. doi: 10.1001/archopht.1962.00960030239015. [DOI] [PubMed] [Google Scholar]
  14. Kern E. R., Overall J. C., Jr, Glasgow L. A. Herpesvirus hominis infection in newborn mice: comparison of the therapeutic efficacy of 1-beta-D-arabinofuranosylcytosine and 9-beta-D-arabinofuranosyladenine. Antimicrob Agents Chemother. 1975 May;7(5):587–595. doi: 10.1128/aac.7.5.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Klein R. J., Friedman-Kien A. E., Brady E. Herpes simplex virus skin infection in hairless mice: treatment with antiviral compounds. Antimicrob Agents Chemother. 1974 Mar;5(3):318–322. doi: 10.1128/aac.5.3.318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Klein R. J., Friedman-Kien A. E. Phosphonoacetic acid-resistant herpes simplex virus infection in hairless mice. Antimicrob Agents Chemother. 1975 Mar;7(3):289–293. doi: 10.1128/aac.7.3.289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lieberman M., Schafer T. W., Came P. E. Chemotherapy of cutaneous herpesvirus infection of hairless mice. J Invest Dermatol. 1973 Apr;60(4):203–206. doi: 10.1111/1523-1747.ep12724476. [DOI] [PubMed] [Google Scholar]
  18. Lowry S. P., Melnick J. L., Rawls W. E. Investigation of plaque formation in chick embryo cells as a biological marker for distinguishing herpes virus type 2 from type 1. J Gen Virol. 1971 Jan;10(1):1–9. doi: 10.1099/0022-1317-10-1-1. [DOI] [PubMed] [Google Scholar]
  19. MacCallum F. O., Juel-Jensen B. E. Herpes simplex virus skin infection in man treated with idoxuridine in dimethyl sulphoxide. Results of double-blind controlled trial. Br Med J. 1966 Oct 1;2(5517):805–807. doi: 10.1136/bmj.2.5517.805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Marks M. I. Variables influencing the in vitro susceptibilities of herpes simplex viruses to antiviral drugs. Antimicrob Agents Chemother. 1974 Jul;6(1):34–38. doi: 10.1128/aac.6.1.34. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Melnick J. L., Rawls W. E. Herpesvirus type 2 and cervical carcinoma. Ann N Y Acad Sci. 1970 Oct 30;174(2):993–998. doi: 10.1111/j.1749-6632.1970.tb45620.x. [DOI] [PubMed] [Google Scholar]
  22. Myers M. G., Oxman M. N., Clark J. E., Arndt K. A. Failure of neutral-red photodynamic inactivation in recurrent herpes simplex virus infections. N Engl J Med. 1975 Nov 6;293(19):945–949. doi: 10.1056/NEJM197511062931901. [DOI] [PubMed] [Google Scholar]
  23. Nahmias A. J., Alford C. A., Korones S. B. Infection of the newborn with herpesvirus hominis. Adv Pediatr. 1970;17:185–226. [PubMed] [Google Scholar]
  24. Nahmias A. J., Dowdle W. R., Naib Z. M., Josey W. E., McLone D., Domescik G. Genital infection with type 2 Herpes virus hominis. A commonly occurring venereal disease. Br J Vener Dis. 1969 Dec;45(4):294–298. doi: 10.1136/sti.45.4.294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pavan-Langston D. Clinical evaluation of adenine arabinoside and idoxuridine in the treatment of ocular herpes simplex. Am J Ophthalmol. 1975 Sep;80(3 Pt 2):495–502. doi: 10.1016/0002-9394(75)90214-7. [DOI] [PubMed] [Google Scholar]
  26. Person D. A., Sheridan P. J., Herrmann E. C. Sensitivity of Types 1 and 2 Herpes Simplex Virus to 5-Iodo-2'-Deoxyuridine and 9-beta-d-Arabinofuranosyladenine. Infect Immun. 1970 Dec;2(6):815–820. doi: 10.1128/iai.2.6.815-820.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Renis H. E. Genital infection of female hamsters with herpesvirus hominis type 2 (HVH-2). Proc Soc Exp Biol Med. 1975 Dec;150(3):723–727. doi: 10.3181/00379727-150-39114. [DOI] [PubMed] [Google Scholar]
  28. Shipkowitz N. L., Bower R. R., Appell R. N., Nordeen C. W., Overby L. R., Roderick W. R., Schleicher J. B., Von Esch A. M. Suppression of herpes simplex virus infection by phosphonoacetic acid. Appl Microbiol. 1973 Sep;26(3):264–267. doi: 10.1128/am.26.3.264-267.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sloan B. J., Miller F. A., McLean I. W., Jr Treatment of herpes simplex virus types 1 and 2 encephalitis in mice with 9-beta-D-arabinofuranosyladenine. Antimicrob Agents Chemother. 1973 Jan;3(1):74–80. doi: 10.1128/aac.3.1.74. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Taylor P. K., Doherty N. R. Comparison of the treatment of herpes genitalis in men with proflavine photoinactivation, idoxuridine ointment, and normal saline. Br J Vener Dis. 1975 Apr;51(2):125–129. doi: 10.1136/sti.51.2.125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tomlinson A. H., Maccallum F. O. The effect of 5-iodo-2'-deoxyuridine on herpes simplex virus infections in guinea-pig skin. Br J Exp Pathol. 1968 Jun;49(3):277–282. [PMC free article] [PubMed] [Google Scholar]
  32. UNDERWOOD G. E. Activity of 1-beta-D-arabinofuranosylcytosine hydrochloride against herpes simplex keratitis. Proc Soc Exp Biol Med. 1962 Dec;111:660–664. doi: 10.3181/00379727-111-27884. [DOI] [PubMed] [Google Scholar]
  33. Whitley R. J., Ch'ien L. T., Dolin R., Galasso G. J., Alford C. A., Jr Adenine arabinoside therapy of herpes zoster in the immunosuppressed. NIAID collaborative antiviral study. N Engl J Med. 1976 May 27;294(22):1193–1199. doi: 10.1056/NEJM197605272942201. [DOI] [PubMed] [Google Scholar]
  34. Wohlenberg C. R., Walz M. A., Notkins A. L. Efficacy of phosphonoacetic acid on herpes simplex virus infection of sensory ganglia. Infect Immun. 1976 May;13(5):1519–1521. doi: 10.1128/iai.13.5.1519-1521.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]

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