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 influence d by iron. Hence, decreasing the availability of iron may inhibit HIV-1 rep lication. Deferoxamine and deferiprone, both forming catalytically inactive iron-chelator complexes, and bleomycin, by use of which iron catalyzes oxi dative nucleic acid destruction, were investigated. Expression of p24 antig en in human monocyte-derived macrophages and peripheral blood lymphocytes ( PBL) was reduced by all 3 iron chelators. In PBL, p24 reduction was mirrore d by a decrease in proliferation after incubation with deferoxamine or defe riprone, suggesting that viral inhibition is closely linked to a decrease i n cellular proliferation. In contrast, clinically relevant bleomycin concen trations reduced p24 levels by similar to 50% without affecting proliferati on. 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 o f action could be of additional benefit in antiretroviral combination thera py.