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 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.
Georgiou
N A
NA
Department of Internal Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. n.georgiou@lab.azu.nl
van der Bruggen
T
T
Oudshoorn
M
M
Nottet
H S
HS
Marx
J J
JJ
van Asbeck
B S
BS
D019380:Anti-HIV Agents / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic; D000077543:Deferiprone; D003676:Deferoxamine / Q000494:pharmacology*; D016049:Didanosine / Q000494:pharmacology; D004357:Drug Synergism; D016655:HIV Core Protein p24 / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000502:physiology / Q000821:virology; D008264:Macrophages / Q000502:physiology / Q000821:virology; D009000:Monocytes / Q000502:physiology / Q000821:virology; D011728:Pyridones / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D016655:HIV Core Protein p24; D007502:Iron Chelating Agents; D011728:Pyridones; D001761:Bleomycin; D000077543:Deferiprone; D003676:Deferoxamine; D016049:Didanosine