CD154-CD40-induced reactivation of latent HIV-1 infection

Academic Article

Abstract

  • Reservoirs of latent HIV-1 in T cells and macrophages pose one of the major obstacles that hamper final eradication of HIV-1 from infected patients. Targeting costimulatory molecules expressed on cell types harboring latent HIV-1 to achieve reactivation may provide a new approach to overcome this problem. One such molecule is CD40, a member of the tumor necrosis factor (TNF)-receptor family. Using THP89GFP cells as a model for latently infected macrophages, we demonstrate that trimeric forms of recombinant CD154 allow for the direct reactivation of latent HIV-1 infection. Reactivation is augmented by the release of TNF-α. The presence of TNF-α is also crucial for the expression of late structural genes such as p24 Gag. In addition, levels of secreted TNF-α are sufficiently high to reactivate latent HIV-1 in a latently HIV-1-infected T-cell line (J89GFP). Taken together, our results demonstrate that costimulatory molecules may be attractive targets to reactivate latent HIV-1 in infected patients. © 2003 Elsevier Science (USA). All rights reserved.
  • Published In

  • Virology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Kutsch O; Levy DN; Kosloff BR; Shaw GM; Benveniste EN
  • Start Page

  • 261
  • End Page

  • 270
  • Volume

  • 314
  • Issue

  • 1