Kinase control prevents HIV-1 reactivation in spite of high levels of induced NF-κB activity

Academic Article


  • Despite its clinical importance, the molecular biology of HIV-1 latency control is at best partially understood, and the literature remains conflicting. The most recent description that latent HIV-1 is integrated into actively expressed host genes has further confounded the situation. This lack of molecular understanding complicates our efforts to identify therapeutic compounds or strategies that could reactivate latent HIV-1 infection in patients, a prerequisite for the eradication of HIV-1 infection. Currently, many therapeutic development efforts operate under the assumption that a restrictive histone code could govern latent infection and that either dissipation of the histone-based restrictions or NF-κB activation could be sufficient to trigger HIV-1 reactivation. We here present data that suggest an additional, higher level of molecular control. During a high-content drug screening effort, we identified AS601245 as a potent inhibitor of HIV-1 reactivation in latently infected primary T cells and T cell lines. In either system, AS601245 inhibited HIV-1 reactivation despite high levels of induced NF-κB activation. This finding suggests the presence of a gatekeeper kinase activity that controls latent HIV-1 infection even in the presence of high levels of NF-κB activity. Potential therapeutic stimuli that do not target this gatekeeper kinase will likely fail to trigger efficient system-wide HIV-1 reactivation. © 2012, American Society for Microbiology.
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    Digital Object Identifier (doi)

    Author List

  • Wolschendorf F; Bosque A; Shishido T; Duverger A; Jones J; Planelles V; Kutsch O
  • Start Page

  • 4548
  • End Page

  • 4558
  • Volume

  • 86
  • Issue

  • 8