Amphotericin-B-mediated reactivation of latent HIV-1 infection.
To date, attempts to eliminate HIV-1 infection from its latent reservoirs, a prerequisite for the development of a curative treatment strategy for HIV-1 infection, have been unsuccessful. We demonstrate that the FDA approved antifungal agent amphotericin B efficiently reactivates HIV-1 infection in THP89GFP cells, a model of HIV-1 latency in macrophages. Although amphotericin B does not directly reactivate latent HIV-1 infection in T cells (e.g., J89GFP), amphotericin-B-stimulated macrophages (THP89GFP cells or primary macrophages) when cocultured with J89GFP cells can induce HIV-1 reactivation in these cells in trans. Because of the close proximity of antigen presenting macrophages and T cells in the primary lymphoid organs, such interaction between antigen presenting macrophages and T cells are frequent, and it seems reasonable to assume that trans-reactivation strategies hold promise to also reactivate latent HIV-1 infection in vivo.
Jones
J
J
Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA,
Kosloff
B R
BR
Benveniste
E N
EN
Shaw
G M
GM
Kutsch
O
O
D000584:Amiloride / Q000494:pharmacology; D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D015870:Gene Expression; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009570:Nitriles / Q000494:pharmacology; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014775:Virus Activation / Q000187:drug effects*; D017735:Virus Latency / Q000187:drug effects*
D000935:Antifungal Agents; D002070:Butadienes; D009570:Nitriles; D017923:Sodium-Hydrogen Exchangers; D014409:Tumor Necrosis Factor-alpha; C113580:U 0126; D000584:Amiloride; D000666:Amphotericin B; D048049:Extracellular Signal-Regulated MAP Kinases