Mechanism of inhibitory effect of dextran sulfate and heparin on replication of human immunodeficiency virus in vitro

Proc Natl Acad Sci U S A. 1988 Aug;85(16):6132-6. doi: 10.1073/pnas.85.16.6132.

Abstract

The sulfated polysaccharides dextran sulfate and heparin have proved to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) in vitro. Dextran sulfate (Mr 5000) and heparin (Mr 15,000) completely protected MT-4 cells against HIV-1-induced cytopathogenicity at a concentration of 25 micrograms/ml. Their 50% inhibitory concentrations were 9.1 micrograms/ml (dextran sulfate) and 7.0 micrograms/ml (heparin), respectively. No toxicity for the host cells was observed with these compounds at a concentration of 625 micrograms/ml. The anti-HIV-1 activity of heparins of various molecular weights correlated well with their anticoagulant activity. On the other hand, with dextran sulfates of low molecular weight (5000, 8000) a significant inhibitory effect on HIV-1 was achieved at a concentration that was not markedly inhibitory to the blood coagulation process. Dextran sulfate and heparin were not inhibitory to HIV-1 reverse transcriptase unless they were used at concentrations in excess of those that inhibited HIV-1 replication. They were highly effective against HIV-1 replication even when present only during the 2-hr virus adsorption period. Studies using radiolabeled HIV-1 virions indicated that dextran sulfate and heparin inhibit virus adsorption to the host cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adsorption
  • Anticoagulants / pharmacology
  • Dextran Sulfate
  • Dextrans / pharmacology*
  • HIV / drug effects*
  • Heparin / blood
  • Heparin / pharmacology*
  • Peptide Fragments / pharmacology
  • Reverse Transcriptase Inhibitors
  • Virus Replication / drug effects*

Substances

  • Anticoagulants
  • Dextrans
  • Peptide Fragments
  • Reverse Transcriptase Inhibitors
  • Heparin
  • Dextran Sulfate