title: Cell specific uptake of antiretroviral drugs: AZT coupled to LDL inhibits HIV replication in human macrophages.
abstract: 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.
authors.affiliation: Freie Universität Berlin, Institut für Biochemie, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Mankertz
authors.forename: H
authors.initials: H
authors.lastname: von Baeyer
authors.forename: K
authors.initials: K
authors.lastname: Rokos
authors.forename: M
authors.initials: M
authors.lastname: Nündel
authors.forename: G
authors.initials: G
authors.lastname: Pauli
authors.forename: E
authors.initials: E
authors.lastname: Riedel
mesh_terms: 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*
chemical_list: D000998:Antiviral Agents; D004337:Drug Carriers; D008077:Lipoproteins, LDL; D015215:Zidovudine