Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1975 May;7(5):587–595. doi: 10.1128/aac.7.5.587

Herpesvirus hominis Infection in Newborn Mice: Comparison of the Therapeutic Efficacy of 1-β-d-Arabinofuranosylcytosine and 9-β-d-Arabinofuranosyladenine1

Earl R Kern *, James C Overall Jr , Lowell A Glasgow
PMCID: PMC429187  PMID: 1147590

Abstract

Intranasal inoculation of newborn mice with Herpesvirus hominis type 2 provides an experimental infection that closely resembles disseminated herpesvirus infection of human newborn infants. After inoculation of mice, the virus multiplies in the respiratory tract and is disseminated through the blood to the liver and spleen and to the brain by both a viremia and nerve route transmission. Although therapy with 1-β-d-arabinofuranosylcytosine (ara-C) did not reduce final mortality, it did increase the mean survival time by 1 day. This effect on the mean survival time was associated with a 1-day delay in the appearance of herpesvirus in the blood, liver, and spleen and a reduction of virus replication in lung and brain for 1 day as compared with untreated control animals. Treatment with 9-β-d-arabinofuranosyladenine (ara-A) likewise had no effect on final mortality, but increased the mean survival time by 2 days. Therapy with ara-A delayed or suppressed virus replication in blood, lung, liver, spleen, and brain for 2 days. Although treatment with either ara-C or ara-A in this experimental H. hominis type 2 infection resulted in a temporary delay and/or suppression of viral replication in several target organs, neither compound was completely effective in inhibiting viral replication or in protecting animals from eventual death due to the infection.

Full text

PDF
591

Selected References

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

  1. Allen L. B., Sidwell R. W. Target-organ treatment of neurotropic virus diseases: efficacy as a chemotherapy tool and comparison of activity of adenine arabinoside, cytosine arabinoside, idoxuridine, and trifluorothymidine. Antimicrob Agents Chemother. 1972 Sep;2(3):229–233. doi: 10.1128/aac.2.3.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BRINK J. J., LEPAGE G. A. METABOLIC EFFECTS OF 9-D-ARABINOSYLPURINES IN ASCITES TUMOR CELLS. Cancer Res. 1964 Feb;24:312–318. [PubMed] [Google Scholar]
  3. BRINK J. J., LEPAGE G. A. METABOLISM AND DISTRIBUTION OF 9-BETA-D-ARABINOFURANOSYLADENINE IN MOUSE TISSUES. Cancer Res. 1964 Jul;24:1042–1049. [PubMed] [Google Scholar]
  4. BUTHALA D. A. CELL CULTURE STUDIES ON ANTIVIRAL AGENTS. I. ACTION OF CYTOSINE ARABINOSIDE AND SOME COMPARISONS WITH 5-IODO-2-DEOXYURIDINE. Proc Soc Exp Biol Med. 1964 Jan;115:69–77. doi: 10.3181/00379727-115-28834. [DOI] [PubMed] [Google Scholar]
  5. Borsa J., Whitmore G. F., Valeriote F. A., Collins D., Bruce W. R. Studies on the persistence of methotrexate, cytosine arabinoside, and leucovorin in serum of mice. J Natl Cancer Inst. 1969 Feb;42(2):235–242. [PubMed] [Google Scholar]
  6. Camiener G. W., Smith C. G. Studies of the enzymatic deamination of cytosine arabinoside. I. Enzyme distribution and species specificity. Biochem Pharmacol. 1965 Oct;14(10):1405–1416. doi: 10.1016/0006-2952(65)90175-9. [DOI] [PubMed] [Google Scholar]
  7. Ch'ien L. T., Cannon N. J., Charamella L. J., Dismukes W. E., Whitley R. J., Buchanan R. A., Alford C. A., Jr Effect of adenine arabinoside on severe Herpesvirus hominis infections in man. J Infect Dis. 1973 Nov;128(5):658–663. doi: 10.1093/infdis/128.5.658. [DOI] [PubMed] [Google Scholar]
  8. Chow A. W., Roland A., Fiala M., Hryniuk W., Weil M. L., Geme J. S., Jr, Guze L. B. Cytosine arabinoside therapy for herpes simplex encephalitis--clinical experience with six patients. Antimicrob Agents Chemother. 1973 Mar;3(3):412–417. doi: 10.1128/aac.3.3.412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dixon R. L., Adamson R. H. Antitumor activity and pharmacologic disposition of cytosine arabinoside (NSC-63878). Cancer Chemother Rep. 1965 Oct;48:11–16. [PubMed] [Google Scholar]
  10. Fiala M., Chow A., Guze L. B. Susceptibility of herpesviruses to cytosine arabinoside: standardization of susceptibility test procedure and relative resistance of herpes simplex type 2 strains. Antimicrob Agents Chemother. 1972 Apr;1(4):354–357. doi: 10.1128/aac.1.4.354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hirsch M. S., Zisman B., Allison A. C. Macrophages and age-dependent resistance to Herpes simplex virus in mice. J Immunol. 1970 May;104(5):1160–1165. [PubMed] [Google Scholar]
  12. Hryniuk W., Foerster J., Shojania M., Chow A. Cytarabine for herpesvirus infections. JAMA. 1972 Feb;219(6):715–718. [PubMed] [Google Scholar]
  13. JOHNSON R. T. THE PATHOGENESIS OF HERPES VIRUS ENCEPHALITIS. II. A CELLULAR BASIS FOR THE DEVELOPMENT OF RESISTANCE WITH AGE. J Exp Med. 1964 Sep 1;120:359–374. doi: 10.1084/jem.120.3.359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. 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]
  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. Miller F. A., Sloan B. J., Silverman C. A. Antiviral activity of 9-beta-D-arabinofuranosyladenine. VI. Effect of delayed treatment on herpes simplex virus in mice. Antimicrob Agents Chemother (Bethesda) 1969;9:192–195. [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. Olson L. C., Buescher E. L., Artenstein M. S., Parkman P. D. Herpesvirus infections of the human central nervous system. N Engl J Med. 1967 Dec 14;277(24):1271–1277. doi: 10.1056/NEJM196712142772401. [DOI] [PubMed] [Google Scholar]
  22. Overall J. C., Jr, Glasgow L. A. Virus infections of the fetus and newborn infant. J Pediatr. 1970 Aug;77(2):315–333. doi: 10.1016/s0022-3476(70)80346-8. [DOI] [PubMed] [Google Scholar]
  23. Panitch H. S., Baringer J. R. Experimental herpes simplex encephalitis. Treatment with pyrimidine nucleosides. Arch Neurol. 1973 Jun;28(6):371–375. doi: 10.1001/archneur.1973.00490240031003. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Plummer G., Ingerson A. P. Iododeoxyuridine and herpesviral encephalitis: lack of inhibitory action against low-grade viral replication. Antimicrob Agents Chemother. 1974 Jun;5(6):672–673. doi: 10.1128/aac.5.6.672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Renis H. E. Antiviral activity of cytarabine in herpesvirus-infected rats. Antimicrob Agents Chemother. 1973 Oct;4(4):439–444. doi: 10.1128/aac.4.4.439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  28. 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]

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

RESOURCES