Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1991 Oct;35(10):2147–2150. doi: 10.1128/aac.35.10.2147

Evaluation of antiviral activity and toxicity of dextran sulfate in feline leukemia virus-infected cats.

L E Mathes 1, K A Hayes 1, C L Swenson 1, P J Polas 1, S E Weisbrode 1, G J Kociba 1
PMCID: PMC245344  PMID: 1662026

Abstract

The feline leukemia virus (FeLV) disease model was used to conduct a toxicity and antiretrovirus efficacy trial of dextran sulfate (DS; molecular mass, 7,000 to 8,000 Da). In vitro, FeLV infection of feline lymphoid cells was inhibited by 10 micrograms of DS per ml. DS was administered to cats by continuous intravenous infusion at doses of 600, 120, 24, or 4.8 mg/kg of body weight per day, beginning 24 h before FeLV challenge. Doses of 24 mg/kg/day and more were excessively toxic, causing intestinal lesions and death. Similar changes were observed in unchallenged animals receiving 24 mg/kg/day, indicating that toxicity was DS mediated. The dosage of 4.8 mg/kg/day was subtoxic but did not prevent the induction and persistence of FeLV viremia. The results demonstrate that DS by continuous intravenous infusion is excessively toxic at high doses and ineffective at preventing FeLV infection at a subtoxic dose in the FeLV cat model.

Full text

PDF
2147

Selected References

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

  1. Abrams D. I., Kuno S., Wong R., Jeffords K., Nash M., Molaghan J. B., Gorter R., Ueno R. Oral dextran sulfate (UA001) in the treatment of the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. Ann Intern Med. 1989 Feb 1;110(3):183–188. doi: 10.7326/0003-4819-110-3-183. [DOI] [PubMed] [Google Scholar]
  2. Bagasra O., Lischner H. W. Activity of dextran sulfate and other polyanionic polysaccharides against human immunodeficiency virus. J Infect Dis. 1988 Nov;158(5):1084–1087. doi: 10.1093/infdis/158.5.1084. [DOI] [PubMed] [Google Scholar]
  3. Chang R. S., Tabba H. D., He Y. S., Smith K. M. Dextran sulfate as an inhibitor against the human immunodeficiency virus. Proc Soc Exp Biol Med. 1988 Dec;189(3):304–309. doi: 10.3181/00379727-189-42811. [DOI] [PubMed] [Google Scholar]
  4. Fischinger P. J., Blevins C. S., Nomura S. Simple, quantitative assay for both xenotropic murine leukemia and ecotropic feline leukemia viruses. J Virol. 1974 Jul;14(1):177–179. doi: 10.1128/jvi.14.1.177-179.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Golomb M., Grandgenett D. P. Endonuclease activity of purified RNA-directed DNA polymerase from avian myeloblastosis virus. J Biol Chem. 1979 Mar 10;254(5):1606–1613. [PubMed] [Google Scholar]
  6. Hardy W. D., Jr, Hirshaut Y., Hess P. Detection of the feline leukemia virus and other mammalian oncornaviruses by immunofluorescence. Bibl Haematol. 1973;39:778–799. doi: 10.1159/000427906. [DOI] [PubMed] [Google Scholar]
  7. Hoover E. A., Mathes L. E., Rojko J. L., Schaller J. P., Olsen R. G. Modifications of the immunofluorescence assay for feline leukemia virus group-specific antigens. Am J Vet Res. 1978 Dec;39(12):1877–1880. [PubMed] [Google Scholar]
  8. Ito M., Baba M., Sato A., Pauwels R., De Clercq E., Shigeta S. Inhibitory effect of dextran sulfate and heparin on the replication of human immunodeficiency virus (HIV) in vitro. Antiviral Res. 1987 Jul;7(6):361–367. doi: 10.1016/0166-3542(87)90018-0. [DOI] [PubMed] [Google Scholar]
  9. Larnicol N., Augery Y., Le Bousse-Kerdiles C., Degiorgis V., Chermann J. C., Teze A., Jasmin C. In vivo effect of a new mineral condensed ion (HPA 39) on murine Friend leukaemia. J Gen Virol. 1981 Jul;55(Pt 1):17–23. doi: 10.1099/0022-1317-55-1-17. [DOI] [PubMed] [Google Scholar]
  10. Lorentsen K. J., Hendrix C. W., Collins J. M., Kornhauser D. M., Petty B. G., Klecker R. W., Flexner C., Eckel R. H., Lietman P. S. Dextran sulfate is poorly absorbed after oral administration. Ann Intern Med. 1989 Oct 1;111(7):561–566. doi: 10.7326/0003-4819-111-7-561. [DOI] [PubMed] [Google Scholar]
  11. Mitsuya H., Looney D. J., Kuno S., Ueno R., Wong-Staal F., Broder S. Dextran sulfate suppression of viruses in the HIV family: inhibition of virion binding to CD4+ cells. Science. 1988 Apr 29;240(4852):646–649. doi: 10.1126/science.2452480. [DOI] [PubMed] [Google Scholar]
  12. Nakashima H., Yoshida O., Tochikura T. S., Yoshida T., Mimura T., Kido Y., Motoki Y., Kaneko Y., Uryu T., Yamamoto N. Sulfation of polysaccharides generates potent and selective inhibitors of human immunodeficiency virus infection and replication in vitro. Jpn J Cancer Res. 1987 Nov;78(11):1164–1168. [PubMed] [Google Scholar]
  13. Nguyen T. D., Bottreau E., Aynaud J. M. Transmissible gastroenteritis (TGE) of swine: in vitro virus attachment and effects of polyanions and polycations. Vet Microbiol. 1987 Sep;14(4):343–354. doi: 10.1016/0378-1135(87)90026-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Polas P. J., Swenson C. L., Sams R., Cheney C. M., Hayes K. A., Tarr M. J., Kociba G. J., Mathes L. E. In vitro and in vivo evidence that the antiviral activity of 2',3'-dideoxycytidine is target cell dependent in a feline retrovirus animal model. Antimicrob Agents Chemother. 1990 Jul;34(7):1414–1421. doi: 10.1128/aac.34.7.1414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rojko J. L., Hoover E. A., Mathes L. E., Olsen R. G., Schaller J. P. Pathogenesis of experimental feline leukemia virus infection. J Natl Cancer Inst. 1979 Sep;63(3):759–768. doi: 10.1093/jnci/63.3.759. [DOI] [PubMed] [Google Scholar]
  16. Solomon J. J., Glatt K. A., Okazaki W. Inhibitory effect of heparin on Rous sarcoma virus. J Bacteriol. 1966 Dec;92(6):1855–1856. doi: 10.1128/jb.92.6.1855-1856.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Swenson C. L., Polas P. J., Mathes L. E. A technique for continuous intravenous infusion in cats. Lab Anim Sci. 1989 Nov;39(6):615–617. [PubMed] [Google Scholar]
  18. Tavares L., Roneker C., Johnston K., Lehrman S. N., de Noronha F. 3'-Azido-3'-deoxythymidine in feline leukemia virus-infected cats: a model for therapy and prophylaxis of AIDS. Cancer Res. 1987 Jun 15;47(12):3190–3194. [PubMed] [Google Scholar]
  19. Theilen G. H., Kawakami T. G., Rush J. D., Munn R. J. Replication of cat leukemia virus in cell suspension cultures. Nature. 1969 May 10;222(5193):589–590. doi: 10.1038/222589b0. [DOI] [PubMed] [Google Scholar]
  20. Tochikura T. S., Nakashima H., Tanabe A., Yamamoto N. Human immunodeficiency virus (HIV)-induced cell fusion: quantification and its application for the simple and rapid screening of anti-HIV substances in vitro. Virology. 1988 Jun;164(2):542–546. doi: 10.1016/0042-6822(88)90570-3. [DOI] [PubMed] [Google Scholar]
  21. Toyoshima K., Vogt P. K. Enhancement and inhibition of avian sarcoma viruses by polycations and polyanions. Virology. 1969 Jul;38(3):414–426. doi: 10.1016/0042-6822(69)90154-8. [DOI] [PubMed] [Google Scholar]
  22. Ueno R., Kuno S. Dextran sulphate, a potent anti-HIV agent in vitro having synergism with zidovudine. Lancet. 1987 Jun 13;1(8546):1379–1379. doi: 10.1016/s0140-6736(87)90681-7. [DOI] [PubMed] [Google Scholar]

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

RESOURCES