Bis-Anthracycline Antibiotics Inhibit Human Immunodeficiency Virus Type 1 Transcription

Academic Article

Abstract

  • The increasing numbers of human immunodeficiency virus type 1 (HIV-1) strains that exhibit resistance to antiretroviral agents used at present require the development of new effective antiretroviral compounds. Tat transactivation was recognized early on as an attractive target for drug interference. To screen for and analyze the effects of compounds that interfere with Tat transactivation, we developed several cell-based reporter systems in which enhanced green fluorescence protein is a direct and quantitative marker of HIV-1 expression or Tat-dependent long terminal repeat activity. Using these reporter cell lines, we found that the bis-anthracycline WP631, a recently developed DNA intercalator, efficiently inhibits HIV-1 expression at subcytotoxic concentrations. WP631 also abrogated acute HIV-1 replication in peripheral blood mononuclear cells infected with various primary virus isolates. We demonstrate that WP631-mediated HIV-1 inhibition is caused by the inhibition of Tat transactivation. The data presented suggest that WP631 could serve as a lead compound for a new type of HIV-1 inhibitor.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Kutsch O; Levy DN; Bates PJ; Decker J; Kosloff BR; Shaw GM; Priebe W; Benveniste EN
  • Start Page

  • 1652
  • End Page

  • 1663
  • Volume

  • 48
  • Issue

  • 5