Cell specific uptake of antiretroviral drugs: AZT coupled to LDL inhibits HIV replication in human macrophages.
Macrophages, besides helper T-lymphocytes, are target cells for the human immunodeficiency virus (HIV). We report on a mechanism to deliver selectively antiretroviral drugs to cells of the monocyte/macrophage lineage. These cells and cells of the endothelium express scavenger receptors which mediate the transport of modified low density lipoprotein (LDL). LDL modified by covalently bound azidothymidine (AZT), a potent inhibitor of HIV replication, is internalized via this pathway into human macrophages. Treatment of HIV-1 infected human macrophages with AZT-LDL showed in vitro efficient inhibition of viral replication. In contrast, HIV replication in T-lymphocytes (Molt 4/8), which do not express scavenger receptors, is not inhibited by AZT-LDL but by free AZT.
Mankertz
J
J
Freie Universität Berlin, Institut für Biochemie, Germany.
von Baeyer
H
H
Rokos
K
K
Nündel
M
M
Pauli
G
G
Riedel
E
E
D000998:Antiviral Agents / Q000378:metabolism* / Q000494:pharmacology*; D004337:Drug Carriers; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D014779:Virus Replication / Q000187:drug effects*; D015215:Zidovudine / Q000378:metabolism* / Q000494:pharmacology*
D000998:Antiviral Agents; D004337:Drug Carriers; D008077:Lipoproteins, LDL; D015215:Zidovudine