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. 1976 Mar;9(3):458–464. doi: 10.1128/aac.9.3.458

Effect of Cytosine Arabinoside and 5-Iodo-2′-Deoxyuridine on a Cytomegalovirus Infection in Newborn Mice1

Douglas K Kelsey *, Earl R Kern , James C Overall Jr , Lowell A Glasgow
PMCID: PMC429552  PMID: 176935

Abstract

Murine cytomegalovirus was inhibited by 0.6 to 1.2 μg of cytosine arabinoside per ml and by 0.3 to 0.6 μg of 5-iodo-2′-deoxyuridine in mouse embryo fibroblast cells. Human cytomegalovirus was inhibited by similar concentrations of the two drugs in WI-38 cells. Intraperitoneal inoculation of suckling mice with 104.5 plaque-forming units of murine cytomegalovirus provides a model for disseminated human cytomegalovirus infection in human newborn infants and is characterized by a widespread infection involving the liver, spleen, lung, kidney, and brain with a 70 to 90% mortality in 7 to 9 days. Treatment with 12.5 mg of cytosine arabinoside per kg or 25 mg of 5-iodo-2′-deoxyuridine per kg twice daily for 8 days had no effect on final mortality or the pathogenesis of the infection with the exception of reduced viral titers in the spleen of 5-iodo-2′-deoxyuridine-treated animals. These data indicate that neither cytosine arabinoside nor 5-iodo-2′-deoxyuridine are effective in the treatment of murine cytomegalovirus infections in suckling mice and suggest that they may be of limited value in the treatment of severe cytomegalovirus infections in human neonates.

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Selected References

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  1. 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]
  2. Emödi G., Sartorius J., Just M., Rohner F., Bühler U. Virus studies in the treatment of congenital cytomegalovirus infections by cytosine arabinoside. Helv Paediatr Acta. 1972 Dec;27(6):557–564. [PubMed] [Google Scholar]
  3. 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]
  4. Henson D., Siegel S. E., Fuccillo D. A., Matthew E., Levine A. S. Cytomegalovirus infections during acute childhood leukemia. J Infect Dis. 1972 Nov;126(5):469–481. doi: 10.1093/infdis/126.5.469. [DOI] [PubMed] [Google Scholar]
  5. Hildebrandt R. J., Monif G. R. Congenital cytomegalovirus infection. Am J Obstet Gynecol. 1969 Oct 1;105(3):349–353. doi: 10.1016/0002-9378(69)90262-2. [DOI] [PubMed] [Google Scholar]
  6. Hildebrandt R. J., Sever J. L., Margileth A. M., Callagan D. A. Cytomegalovirus in the normal pregnant woman. Am J Obstet Gynecol. 1967 Aug 15;98(8):1125–1128. doi: 10.1016/0002-9378(67)90038-5. [DOI] [PubMed] [Google Scholar]
  7. Howard R. J., Miller J., Najarian J. S. Cytomegalovirus-induced immune suppression. II. Cell-mediated immunity. Clin Exp Immunol. 1974 Sep;18(1):119–126. [PMC free article] [PubMed] [Google Scholar]
  8. Howard R. J., Najarian J. S. Cytomegalovirus-induced immune suppression. I. Humoral immunity. Clin Exp Immunol. 1974 Sep;18(1):109–118. [PMC free article] [PubMed] [Google Scholar]
  9. Kanich R. E., Craighead J. E. Cytomegalovirus infection and cytomegalic inclusion disease in renal homotransplant recipients. Am J Med. 1966 Jun;40(6):874–882. doi: 10.1016/0002-9343(66)90202-6. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. Kraybill E. N., Sever J. L., Avery G. B., Movassaghi N. Experimental use of cytosine arabinoside in congenital cytomegalovirus infection. J Pediatr. 1972 Mar;80(3):485–487. doi: 10.1016/s0022-3476(72)80514-6. [DOI] [PubMed] [Google Scholar]
  13. Lang D. J. Cytomegalovirus infections in organ transplantation and post transfusion. An hypothesis. Arch Gesamte Virusforsch. 1972;37(4):365–377. doi: 10.1007/BF01241460. [DOI] [PubMed] [Google Scholar]
  14. McCracken G. H., Jr, Luby J. P. Cytosine arabinoside in the treatment of congenital cytomegalic inclusion disease. J Pediatr. 1972 Mar;80(3):488–493. doi: 10.1016/s0022-3476(72)80515-8. [DOI] [PubMed] [Google Scholar]
  15. Melish M. E., Hanshaw J. B. Congenital cytomegalovirus infection. Developmental progress of infants detected by routine screening. Am J Dis Child. 1973 Aug;126(2):190–194. doi: 10.1001/archpedi.1973.02110190168011. [DOI] [PubMed] [Google Scholar]
  16. Osborn J. E., Blazkovec A. A., Walker D. L. Immunosuppression during acute murine cytomegalovirus infection. J Immunol. 1968 Apr;100(4):835–844. [PubMed] [Google Scholar]
  17. Osborn J. E., Medearis D. N., Jr Suppression of interferon and antibody and multiplication of Newcastle disease virus in cytomegalovirus infected mice. Proc Soc Exp Biol Med. 1967 Feb;124(2):347–353. doi: 10.3181/00379727-124-31740. [DOI] [PubMed] [Google Scholar]
  18. Osborn J. E., Walker D. L. Virulence and attenuation of murine cytomegalovirus. Infect Immun. 1971 Feb;3(2):228–236. doi: 10.1128/iai.3.2.228-236.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. STERN H., ELEK S. D. THE INCIDENCE OF INFECTION WITH CYTOMEGALOVIRUS IN A NORMAL POPULATION. A SEROLOGICAL STUDY IN GREATER LONDON. J Hyg (Lond) 1965 Mar;63:79–87. doi: 10.1017/s0022172400044983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sidwell R. W., Arnett G., Schabel F. M., Jr In vitro effect of a variety of biologically active compounds on human cytomegalovirus. Chemotherapy. 1972;17(4):259–282. doi: 10.1159/000220858. [DOI] [PubMed] [Google Scholar]
  22. Starr J. G., Bart R. D., Jr, Gold E. Inapparent congenital cytomegalovirus infection. Clinical and epidemiologic characteristics in early infancy. N Engl J Med. 1970 May 7;282(19):1075–1078. doi: 10.1056/NEJM197005072821905. [DOI] [PubMed] [Google Scholar]
  23. Stevens D. A., Jordan G. W., Waddell T. F., Merigan T. C. Adverse effect of cytosine arabinoside on disseminated zoster in a controlled trial. N Engl J Med. 1973 Oct 25;289(17):873–878. doi: 10.1056/NEJM197310252891701. [DOI] [PubMed] [Google Scholar]
  24. Wentworth B. B., French L. Plaque assay of cytomegalovirus strains of human origin. Proc Soc Exp Biol Med. 1970 Nov;135(2):253–258. doi: 10.3181/00379727-135-35031. [DOI] [PubMed] [Google Scholar]

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