Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1987 Jul;31(7):1017–1020. doi: 10.1128/aac.31.7.1017

9-(1-3-Dihydroxy-2-propoxymethyl)guanine prevents death but not immunity in murine cytomegalovirus-infected normal and immunosuppressed BALB/c mice.

E J Wilson 1, D N Medearis Jr 1, L A Hansen 1, R H Rubin 1
PMCID: PMC174864  PMID: 2821884

Abstract

Immunosuppressed (from treatment with cortisone acetate and anti-thymocyte globulin) and control adult female BALB/c mice, latently infected with murine cytomegalovirus (MCMV) or lethally challenged (10(6) PFU) with MCMV intraperitoneally, were treated with 9-(1-3-dihydroxy-2-propoxymethyl)guanine (DHPG) intraperitoneally. A dose of 3 mg/kg reduced mortality by 50% in lethally challenged normal mice; 10 mg/kg was required in immunosuppressed mice. When 15 mg/kg was given, the onset of treatment could be delayed for 64 h after lethal challenge. DHPG did not prevent the establishment of latent MCMV infection or immunosuppression-induced reactivation. The antibody titer to MCMV in DHPG-treated mice which survived lethal challenge was 41 (reciprocal of geometric mean) 4 to 5 weeks after inoculation; such mice survived a second lethal challenge. When antiserum treatment was begun 64 h and DHPG was begun 72 h after a lethal challenge, most mice survived; most did not when either treatment alone was begun at those times. In summary, DHPG effectively treated lethal MCMV infection even in immunosuppressed mice and even when treatment onset was delayed for 64 h. Treatment did not alter the establishment or reactivation of latent infections or the induction of effective immunity. The administration of DHPG coupled with antiserum treatment may be even more effective than the administration of either alone.

Full text

PDF

Selected References

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

  1. Chou S. W. Acquisition of donor strains of cytomegalovirus by renal-transplant recipients. N Engl J Med. 1986 May 29;314(22):1418–1423. doi: 10.1056/NEJM198605293142205. [DOI] [PubMed] [Google Scholar]
  2. Dolin R. Antiviral chemotherapy and chemoprophylaxis. Science. 1985 Mar 15;227(4692):1296–1303. doi: 10.1126/science.2983421. [DOI] [PubMed] [Google Scholar]
  3. Felsenstein D., D'Amico D. J., Hirsch M. S., Neumeyer D. A., Cederberg D. M., de Miranda P., Schooley R. T. Treatment of cytomegalovirus retinitis with 9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine. Ann Intern Med. 1985 Sep;103(3):377–380. doi: 10.7326/0003-4819-103-3-377. [DOI] [PubMed] [Google Scholar]
  4. Hirsch M. S., Schooley R. T., Cosimi A. B., Russell P. S., Delmonico F. L., Tolkoff-Rubin N. E., Herrin J. T., Cantell K., Farrell M. L., Rota T. R. Effects of interferon-alpha on cytomegalovirus reactivation syndromes in renal-transplant recipients. N Engl J Med. 1983 Jun 23;308(25):1489–1493. doi: 10.1056/NEJM198306233082501. [DOI] [PubMed] [Google Scholar]
  5. Katzenstein D. A., Crane R. T., Jordan M. C. Successful treatment of murine cytomegalovirus disease does not prevent latent virus infection. J Lab Clin Med. 1986 Aug;108(2):155–160. [PubMed] [Google Scholar]
  6. Mar E. C., Cheng Y. C., Huang E. S. Effect of 9-(1,3-dihydroxy-2-propoxymethyl)guanine on human cytomegalovirus replication in vitro. Antimicrob Agents Chemother. 1983 Oct;24(4):518–521. doi: 10.1128/aac.24.4.518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Martin J. C., Dvorak C. A., Smee D. F., Matthews T. R., Verheyden J. P. 9-[(1,3-Dihydroxy-2-propoxy)methyl]guanine: a new potent and selective antiherpes agent. J Med Chem. 1983 May;26(5):759–761. doi: 10.1021/jm00359a023. [DOI] [PubMed] [Google Scholar]
  8. Masur H., Lane H. C., Palestine A., Smith P. D., Manischewitz J., Stevens G., Fujikawa L., Macher A. M., Nussenblatt R., Baird B. Effect of 9-(1,3-dihydroxy-2-propoxymethyl) guanine on serious cytomegalovirus disease in eight immunosuppressed homosexual men. Ann Intern Med. 1986 Jan;104(1):41–44. doi: 10.7326/0003-4819-104-1-41. [DOI] [PubMed] [Google Scholar]
  9. Plotkin S. A., Drew W. L., Felsenstein D., Hirsch M. S. Sensitivity of clinical isolates of human cytomegalovirus to 9-(1,3-dihydroxy-2-propoxymethyl)guanine. J Infect Dis. 1985 Oct;152(4):833–834. doi: 10.1093/infdis/152.4.833. [DOI] [PubMed] [Google Scholar]
  10. Rubin R. H., Wilson E. J., Barrett L. V., Medearis D. N. Primary cytomegalovirus infection following cardiac transplantation in a murine model. Transplantation. 1984 Mar;37(3):306–310. doi: 10.1097/00007890-198403000-00018. [DOI] [PubMed] [Google Scholar]
  11. Rubin R. H., Wilson E. J., Barrett L. V., Medearis D. N. The protective effects of hyperimmune anti-murine cytomegalovirus antiserum against lethal viral challenge: the case for passive-active immunization. Clin Immunol Immunopathol. 1986 Apr;39(1):151–158. doi: 10.1016/0090-1229(86)90214-x. [DOI] [PubMed] [Google Scholar]
  12. Selgrade M. K., Osborn J. E. Role of macrophages in resistance to murine cytomegalovirus. Infect Immun. 1974 Dec;10(6):1383–1390. doi: 10.1128/iai.10.6.1383-1390.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Shanley J. D., Morningstar J., Jordan M. C. Inhibition of murine cytomegalovirus lung infection and interstitial pneumonitis by acyclovir and 9-(1,3-dihydroxy-2-propoxymethyl)guanine. Antimicrob Agents Chemother. 1985 Aug;28(2):172–175. doi: 10.1128/aac.28.2.172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Shepp D. H., Dandliker P. S., de Miranda P., Burnette T. C., Cederberg D. M., Kirk L. E., Meyers J. D. Activity of 9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine in the treatment of cytomegalovirus pneumonia. Ann Intern Med. 1985 Sep;103(3):368–373. doi: 10.7326/0003-4819-103-3-368. [DOI] [PubMed] [Google Scholar]
  15. Winston D. J., Ho W. G., Lin C. H., Bartoni K., Budinger M. D., Gale R. P., Champlin R. E. Intravenous immune globulin for prevention of cytomegalovirus infection and interstitial pneumonia after bone marrow transplantation. Ann Intern Med. 1987 Jan;106(1):12–18. doi: 10.7326/0003-4819-106-1-12. [DOI] [PubMed] [Google Scholar]

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

RESOURCES