title: Integrase inhibitors effective against human T-cell leukemia virus type 1.
abstract: Drugs targeting the viral enzyme integrase have been in use for several years as part of the treatment regimen for patients with human immunodeficiency virus type 1 (HIV-1), and similar classes of compounds have been shown to inhibit human T-cell leukemia virus type 1 (HTLV-1) integration in vitro. The current study shows that the clinically approved HIV-1 integrase inhibitor, raltegravir, as well as the more recent diketo acid derivative, MK-2048, are active inhibitors of HTLV-1 infection in vitro. These agents were effective in inhibiting cell-free and cell-to-cell transmission of HTLV-1 in lymphoid and nonlymphoid cells. The drugs also inhibited HTLV-1 immortalization of human peripheral blood mononuclear cells. A novel adaptation of the Alu assay for viral integration was used to show that the drugs inhibit viral integration without affecting reverse transcription. These data support the administration of raltegravir and other integrase inhibitors as treatments for patients with HTLV-1-associated diseases.
authors.affiliation: Division of Molecular Oncology, Department of Molecular Microbiology, Washington University School of Medicine, Box 8069, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
authors.forename: Muhammad Esa
authors.initials: ME
authors.lastname: Seegulam
authors.forename: Lee
authors.initials: L
authors.lastname: Ratner
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D011760:Pyrrolidinones / Q000494:pharmacology; D000068898:Raltegravir Potassium; D016662:Virus Integration / Q000187:drug effects
chemical_list: D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium