Bis-Anthracycline Antibiotics Inhibit Human Immunodeficiency Virus Type 1 Transcription

Olaf Kutsch, David Levy, Paula J. Bates, Julie Decker, Barry R. Kosloff, George M. Shaw, W. Priebe, Etty N. Benveniste

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1652-1663
Number of pages12
JournalAntimicrobial Agents and Chemotherapy
Volume48
Issue number5
DOIs
StatePublished - May 2004

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Anthracyclines
HIV-1
Anti-Bacterial Agents
Transcriptional Activation
Intercalating Agents
Anti-Retroviral Agents
Terminal Repeat Sequences
Virus Replication
Blood Cells
Fluorescence
Viruses
Cell Line
WP 631
DNA
Pharmaceutical Preparations
Proteins

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Bis-Anthracycline Antibiotics Inhibit Human Immunodeficiency Virus Type 1 Transcription. / Kutsch, Olaf; Levy, David; Bates, Paula J.; Decker, Julie; Kosloff, Barry R.; Shaw, George M.; Priebe, W.; Benveniste, Etty N.

In: Antimicrobial Agents and Chemotherapy, Vol. 48, No. 5, 05.2004, p. 1652-1663.

Research output: Contribution to journalArticle

Kutsch, O, Levy, D, Bates, PJ, Decker, J, Kosloff, BR, Shaw, GM, Priebe, W & Benveniste, EN 2004, 'Bis-Anthracycline Antibiotics Inhibit Human Immunodeficiency Virus Type 1 Transcription', Antimicrobial Agents and Chemotherapy, vol. 48, no. 5, pp. 1652-1663. https://doi.org/10.1128/AAC.48.5.1652-1663.2004
Kutsch, Olaf ; Levy, David ; Bates, Paula J. ; Decker, Julie ; Kosloff, Barry R. ; Shaw, George M. ; Priebe, W. ; Benveniste, Etty N. / Bis-Anthracycline Antibiotics Inhibit Human Immunodeficiency Virus Type 1 Transcription. In: Antimicrobial Agents and Chemotherapy. 2004 ; Vol. 48, No. 5. pp. 1652-1663.
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