Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1978 Jan;13(1):53–60. doi: 10.1128/aac.13.1.53

Alteration of Mortality and Pathogenesis of Three Experimental Herpesvirus hominis Infections of Mice with Adenine Arabinoside 5′-Monophosphate, Adenine Arabinoside, and Phosphonoacetic Acid†

Earl R Kern 1, James T Richards 2, James C Overall Jr 2, Lowell A Glasgow 2
PMCID: PMC352184  PMID: 204250

Abstract

The therapeutic effectiveness of adenine arabinoside 5′-monophosphate (ara-AMP), adenine arabinoside (ara-A), and phosphonoacetic acid (PAA) was compared in three experimental Herpesvirus hominis type 2 infections of mice. In animals inoculated with H. hominis by the intracerebral or intraperitoneal route, both ara-AMP and ara-A were highly effective in reducing mortality even when treatment was begun 48 to 96 h after viral inoculation. ara-AMP was the most effective in both models in that treatment could be initiated 24 to 48 h later in the course of infection than with ara-A and still confer significant protection. In mice inoculated intraperitoneally, protection due to ara-AMP therapy was associated with reduced replication of virus in visceral organs and complete inhibition of transmission of virus to the brain. PAA treatment of mice inoculated intraperitoneally was effective in reducing mortality only if initiated shortly after infection. Treatment with PAA did not reduce mortality of mice inoculated intracerebrally but did prolong the mean day of death. When mice were inoculated intranasally with H. hominis, none of the three drugs altered final mortality; however, treatment with ara-AMP did prolong the mean day of death. Treatment with ara-AMP effectively reduced viral replication in the lung and liver in this model infection, but failed to prevent transmission of virus through the trigeminal nerves from the nasopharynx to the brain.

Full text

PDF
55

Selected References

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

  1. CHEEVER F. S., DAIKOS G. Studies of the protective effect of gamma globulin against herpes simplex infections in mice. J Immunol. 1950 Jul;65(1):135–141. [PubMed] [Google Scholar]
  2. Cho C. T., Feng K. K., Brahmacupta N. Synergistic antiviral effects of adenine arabinoside and humoral antibodies in experimental encephalitis due to Herpesvirus hominis. J Infect Dis. 1976 Feb;133(2):157–167. doi: 10.1093/infdis/133.2.157. [DOI] [PubMed] [Google Scholar]
  3. Friedman-Kien A. E., Fondak A. A., Klein R. J. Phosphonoacetic acid treatment of shope fibroma and vaccinia virus skin infections in rabbits. J Invest Dermatol. 1976 Feb;66(02):99–102. doi: 10.1111/1523-1747.ep12481437. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Godfrey R. C. Resistance to intracerebral challenge in mice immunized against herpes simplex virus. Br J Exp Pathol. 1972 Oct;53(5):529–539. [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. Griffith J. F., Fitzwilliam J. F., Casagrande S., Butler S. R. Experimental herpes simplex virus encephalitis: Comparative effects of treatment with cytosine arabinoside and adenine arabinoside. J Infect Dis. 1975 Nov;132(5):506–510. doi: 10.1093/infdis/132.5.506. [DOI] [PubMed] [Google Scholar]
  8. JOHNSON R. T. THE PATHOGENESIS OF HERPES VIRUS ENCEPHALITIS. I. VIRUS PATHWAYS TO THE NERVOUS SYSTEM OF SUCKLING MICE DEMONSTRATED BY FLUORESCENT ANTIBODY STAINING. J Exp Med. 1964 Feb 1;119:343–356. doi: 10.1084/jem.119.2.343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kern E. R., Overall J. C., Jr, Glasgow L. A. Herpesvirus hominis infection in newborn mice. I. An experimental model and therapy with iododeoxyuridine. J Infect Dis. 1973 Sep;128(3):290–299. doi: 10.1093/infdis/128.3.290. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Kern E. R., Overall J. C., Jr, Glasgow L. A. Herpesvirus hominis infection in newborn mice: treatment with interferon inducer polyinosinic-polycytidylic acid. Antimicrob Agents Chemother. 1975 Jun;7(6):793–800. doi: 10.1128/aac.7.6.793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kern E. R., Richards J. T., Overall J. C., Jr, Glasgow L. A. Genital Herpesvirus homonis infection in mice. II. Treatment with phosphonoacetic acid, adenine arabinoside, and adenine arabinoside 5'-monophosphate. J Infect Dis. 1977 Apr;135(4):557–567. doi: 10.1093/infdis/135.4.557. [DOI] [PubMed] [Google Scholar]
  13. Lefkowitz E., Worthington M., Conliffe M. A., Baron S. Comparative effectiveness of six antiviral agents in Herpes simplex type 1 infection of mice. Proc Soc Exp Biol Med. 1976 Jul;152(3):337–342. doi: 10.3181/00379727-152-39392. [DOI] [PubMed] [Google Scholar]
  14. Meyer R. F., Varnell E. D., Kaufman H. E. Phosphonoacetic acid in the treatment of experimental ocular herpes simplex infections. Antimicrob Agents Chemother. 1976 Feb;9(2):308–311. doi: 10.1128/aac.9.2.308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Morahan P. S., Kern E. R., Glasgow L. A. Immunomodulator-induced resistance against herpes simplex virus. Proc Soc Exp Biol Med. 1977 Apr;154(4):615–620. doi: 10.3181/00379727-154-39730. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Nahmias A. J., Roizman B. Infection with herpes-simplex viruses 1 and 2. 3. N Engl J Med. 1973 Oct 11;289(15):781–789. doi: 10.1056/NEJM197310112891505. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Overby L. R., Robishaw E. E., Schleicher J. B., Rueter A., Shipkowitz N. L., Mao J. C. Inhibition of herpes simplex virus replication by phosphonoacetic acid. Antimicrob Agents Chemother. 1974 Sep;6(3):360–365. doi: 10.1128/aac.6.3.360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Poste G., Hawkins D. F., Thomlinson J. Herpesvirus hominis infection of the female genital tract. Obstet Gynecol. 1972 Dec;40(6):871–890. [PubMed] [Google Scholar]
  21. 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]
  22. Sidwell R. W., Allen L. B., Huffman J. H., Khwaja T. A., Tolman R. L., Robins R. K. Anti-DNA virus activity of the 5'-nucleotide and 3',5'-cyclic nucleotide of 9-beta-D-arabinofuranosyladenine. Chemotherapy. 1973;19(6):325–340. doi: 10.1159/000221473. [DOI] [PubMed] [Google Scholar]
  23. Tokumaru T. The protective effect of different immunoglobulins against herpetic encephalitis and skin infection in guinea pigs. Arch Gesamte Virusforsch. 1967;22(3):332–348. doi: 10.1007/BF01242954. [DOI] [PubMed] [Google Scholar]
  24. Trobe J. D., Centifanto Y., Zam Z. S., Varnell E., Kaufman H. E. Anti-herpes activity of adenine arabinoside monophosphate. Invest Ophthalmol. 1976 Mar;15(3):196–199. [PubMed] [Google Scholar]
  25. Whitley R. J., Soong S. J., Dolin R., Galasso G. J., Ch'ien L. T., Alford C. A. Adenine arabinoside therapy of biopsy-proved herpes simplex encephalitis. National Institute of Allergy and Infectious Diseases collaborative antiviral study. N Engl J Med. 1977 Aug 11;297(6):289–294. doi: 10.1056/NEJM197708112970601. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES