Inhibition of human immunodeficiency virus type 1 replication in human mononuclear blood cells by the iron chelators deferoxamine, deferiprone, and bleomycin

J Infect Dis. 2000 Feb;181(2):484-90. doi: 10.1086/315223.

Abstract

Replication of human immunodeficiency virus type 1 (HIV-1) can be influenced by iron. Hence, decreasing the availability of iron may inhibit HIV-1 replication. Deferoxamine and deferiprone, both forming catalytically inactive iron-chelator complexes, and bleomycin, by use of which iron catalyzes oxidative nucleic acid destruction, were investigated. Expression of p24 antigen in human monocyte-derived macrophages and peripheral blood lymphocytes (PBL) was reduced by all 3 iron chelators. In PBL, p24 reduction was mirrored by a decrease in proliferation after incubation with deferoxamine or deferiprone, suggesting that viral inhibition is closely linked to a decrease in cellular proliferation. In contrast, clinically relevant bleomycin concentrations reduced p24 levels by approximately 50% without affecting proliferation. When deferoxamine and the nucleoside analogue dideoxyinosine were used in combination, they acted synergistically in inhibiting HIV-1 replication. These observations suggest that iron chelators with different mechanisms of action could be of additional benefit in antiretroviral combination therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / pharmacology
  • Bleomycin / pharmacology*
  • Cytotoxicity, Immunologic
  • Deferiprone
  • Deferoxamine / pharmacology*
  • Didanosine / pharmacology
  • Drug Synergism
  • HIV Core Protein p24 / metabolism
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Iron Chelating Agents / pharmacology*
  • Leukocytes, Mononuclear / virology*
  • Lymphocyte Activation
  • Lymphocytes / physiology
  • Lymphocytes / virology
  • Macrophages / physiology
  • Macrophages / virology
  • Monocytes / physiology
  • Monocytes / virology
  • Pyridones / pharmacology*
  • Virus Replication / drug effects

Substances

  • Anti-HIV Agents
  • HIV Core Protein p24
  • Iron Chelating Agents
  • Pyridones
  • Bleomycin
  • Deferiprone
  • Deferoxamine
  • Didanosine