Inhibition of ecto-ATPase activities impairs HIV-1 infection of macrophages.

Abstract

Nucleotides and nucleosides are secreted into extracellular media at different concentrations as a consequence of different physiologic and pathological conditions. Ecto-nucleotidases, enzymes present on the surface of most cells, hydrolyze these extracellular nucleotides and reduce the concentration of them, thus affecting the activation of different nucleotide and nucleoside receptors. Also, ecto-nucleotidases are present in a number of microorganisms and play important roles in host-pathogen interactions. Here, we characterized the ecto-ATPase activities present on the surface of HIV-1 particle and human macrophages as well. We found that the kinetic properties of HIV-1 and macrophage ecto-ATPases are similar, suggesting that the enzyme is the same. This ecto-ATPase activity was increased in macrophages infected in vitro with HIV-1. Using three different non-related ecto-ATPase inhibitors-POM-1, ARL67156 and BG0-we showed that the inhibition of these macrophage and viral ecto-ATPase activities impairs HIV-1 infection. In addition, we also found that elevated extracellular concentrations of ATP inhibit HIV-1 production by infected macrophages.

• Authors: Julieta Schachter, Kelly Valcárcel Delgado, Victor Barreto-de-Souza, Dumith Chequer Bou-Habib, Pedro Muanis Persechini, José Roberto Meyer-Fernandes
• Journal: Immunobiology (Immunobiology) Vol. 220 Issue 5 Pg. 589-96 (May 2015) ISSN: 1878-3279 [Electronic] Netherlands
• PMID: 25577295 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier GmbH. All rights reserved.

Chemical References

• 6-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP
• Enzyme Inhibitors
• Naphthalenes
• Polymers
• Tungsten Compounds
• Adenosine Triphosphate
• Adenosine Triphosphatases
• ectoATPase

Topics

• Adenosine Triphosphatases (antagonists & inhibitors, metabolism)
• Adenosine Triphosphate (analogs & derivatives, metabolism, pharmacology)
• Cells, Cultured
• Enzyme Inhibitors (pharmacology)
• Extracellular Space (metabolism)
• HIV Infections (enzymology)
• HIV-1 (drug effects)
• Host-Parasite Interactions
• Humans
• Kinetics
• Macrophages (drug effects, metabolism, virology)
• Naphthalenes (pharmacology)
• Polymers (pharmacology)
• Tungsten Compounds (pharmacology)