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Bouchat, Sophie; Delacourt, Nadège; Kula, Anna; Darcis, Gilles; Van Driessche, Benoit; Corazza, Francis; Gatot, Jean‐Stéphane; Melard, Adeline; Vanhulle, Caroline; Kabeya, Kabamba; Pardons, Marion; Avettand‐Fenoel, Véronique; Clumeck, Nathan; De Wit, Stéphane; Rohr, Olivier; Rouzioux, Christine; Van Lint, Carine

Sequential treatment with 5‐aza‐2′‐deoxycytidine and deacetylase inhibitors reactivates HIV‐1

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  • Medientyp: E-Artikel
  • Titel: Sequential treatment with 5‐aza‐2′‐deoxycytidine and deacetylase inhibitors reactivates HIV‐1
  • Beteiligte: Bouchat, Sophie; Delacourt, Nadège; Kula, Anna; Darcis, Gilles; Van Driessche, Benoit; Corazza, Francis; Gatot, Jean‐Stéphane; Melard, Adeline; Vanhulle, Caroline; Kabeya, Kabamba; Pardons, Marion; Avettand‐Fenoel, Véronique; Clumeck, Nathan; De Wit, Stéphane; Rohr, Olivier; Rouzioux, Christine; Van Lint, Carine
  • Erschienen: Springer Science and Business Media LLC, 2016
  • Erschienen in: EMBO Molecular Medicine
  • Sprache: Englisch
  • DOI: 10.15252/emmm.201505557
  • ISSN: 1757-4676; 1757-4684
  • Schlagwörter: Molecular Medicine
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Reactivation of <jats:styled-content style="fixed-case">HIV</jats:styled-content> gene expression in latently infected cells together with an efficient <jats:styled-content style="fixed-case">cART</jats:styled-content> has been proposed as an adjuvant therapy aimed at eliminating/decreasing the reservoir size. Results from <jats:styled-content style="fixed-case">HIV</jats:styled-content> clinical trials using deacetylase inhibitors (<jats:styled-content style="fixed-case">HDACI</jats:styled-content>s) question the efficiency of these latency‐reversing agents (<jats:styled-content style="fixed-case">LRA</jats:styled-content>s) used alone and underline the need to evaluate other <jats:styled-content style="fixed-case">LRA</jats:styled-content>s in combination with <jats:styled-content style="fixed-case">HDACI</jats:styled-content>s. Here, we evaluated the therapeutic potential of a demethylating agent (5‐AzadC) in combination with clinically tolerable <jats:styled-content style="fixed-case">HDACI</jats:styled-content>s in reactivating <jats:styled-content style="fixed-case">HIV</jats:styled-content>‐1 from latency first <jats:italic>in vitro</jats:italic> and next <jats:italic>ex vivo</jats:italic>. We showed that a sequential treatment with 5‐AzadC and <jats:styled-content style="fixed-case">HDACI</jats:styled-content>s was more effective than the corresponding simultaneous treatment both <jats:italic>in vitro</jats:italic> and <jats:italic>ex vivo</jats:italic>. Interestingly, only two of the sequential <jats:styled-content style="fixed-case">LRA</jats:styled-content> combinatory treatments tested induced <jats:styled-content style="fixed-case">HIV</jats:styled-content>‐1 particle recovery in a higher manner than the drugs alone <jats:italic>ex vivo</jats:italic> and at concentrations lower than the human tolerable plasmatic concentrations. Taken together, our data reveal the benefit of using combinations of 5‐AzadC with an <jats:styled-content style="fixed-case">HDACI</jats:styled-content> and, for the first time, the importance of treatment time schedule for <jats:styled-content style="fixed-case">LRA</jats:styled-content> combinations in order to reactivate <jats:styled-content style="fixed-case">HIV</jats:styled-content>.</jats:p>
  • Zugangsstatus: Freier Zugang