Inhibition of Human Immunodeficiency Virus Type 1 Replication in Human Mononuclear Blood Cells by the Iron Chelators Deferoxamine, Deferiprone, and Bleomycin

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 oxi...

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Bibliographic Details
Published in:The Journal of infectious diseases 2000-02, Vol.181 (2), p.484-490
Main Authors: Georgiou, Niki A., van der Bruggen, Tjomme, Oudshoorn, Maroeska, Nottet, Hans S. L. M., Marx, Joannes J. M., van Asbeck, B. Sweder
Format: Article
Language:English
Subjects:
Anti-HIV Agents - pharmacology
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiviral agents
Biological and medical sciences
Bleomycin - pharmacology
Blood
Blood cells
Cytotoxicity
Cytotoxicity, Immunologic
Deferoxamine - pharmacology
Didanosine - pharmacology
DNA
Drug Synergism
HIV
HIV 1
HIV Core Protein p24 - metabolism
HIV-1 - drug effects
HIV-1 - physiology
Humans
Iron Chelating Agents - pharmacology
Leukocytes, Mononuclear - virology
Lymphocyte Activation
Lymphocytes
Lymphocytes - physiology
Lymphocytes - virology
Macrophages - physiology
Macrophages - virology
Major Articles
Medical sciences
Monocytes - physiology
Monocytes - virology
Percentages
Pharmacology. Drug treatments
Pyridones - pharmacology
Ribonucleotides
T lymphocytes
Virus Replication - drug effects
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Summary: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 ∼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.
ISSN:0022-1899
1537-6613
DOI:10.1086/315223