title: 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.affiliation: Campus de Xerem, Universidade Federal do Rio de Janeiro - UFRJ, Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia para Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAm), Conselho Nacional de Desenvolvimento Científico e Tecnológico, Rio de Janeiro, RJ, Brazil. Electronic address: julieta@xerem.ufrj.br.
authors.forename: Julieta
authors.initials: J
authors.lastname: Schachter
authors.affiliation: Instituto Nacional de Ciência e Tecnologia para Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAm), Conselho Nacional de Desenvolvimento Científico e Tecnológico, Rio de Janeiro, RJ, Brazil; Instituto de Biofísica, Carlos Chagas Filho (IBCCF), Universidade Federal do Rio de Janeiro - UFRJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Kelly Valcárcel
authors.initials: KV
authors.lastname: Delgado
authors.affiliation: Laboratório de Pesquisa sobre o Timo, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Victor
authors.initials: V
authors.lastname: Barreto-de-Souza
authors.affiliation: Laboratório de Pesquisa sobre o Timo, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Dumith Chequer
authors.initials: DC
authors.lastname: Bou-Habib
authors.affiliation: Instituto Nacional de Ciência e Tecnologia para Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAm), Conselho Nacional de Desenvolvimento Científico e Tecnológico, Rio de Janeiro, RJ, Brazil; Instituto de Biofísica, Carlos Chagas Filho (IBCCF), Universidade Federal do Rio de Janeiro - UFRJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Pedro Muanis
authors.initials: PM
authors.lastname: Persechini
authors.affiliation: Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro- UFRJ, Rio de Janeiro, RJ, Brazil. Electronic address: meyer@bioqmed.ufrj.br.
authors.forename: José Roberto
authors.initials: JR
authors.lastname: Meyer-Fernandes
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D015658:HIV Infections / Q000201:enzymology*; D015497:HIV-1 / Q000187:drug effects*; D006790:Host-Parasite Interactions; D006801:Humans; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D009281:Naphthalenes / Q000494:pharmacology; D011108:Polymers / Q000494:pharmacology; D017973:Tungsten Compounds / Q000494:pharmacology
chemical_list: C092431:6-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D011108:Polymers; D017973:Tungsten Compounds; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C027201:ectoATPase
keywords: CD39; Ecto-ATPase; HIV infection; Infected macrophages