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

Olaf Kutsch, David N. Levy, Barry R. Kosloff, George M. Shaw, Etty N. Benveniste

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)261-270
Number of pages10
JournalVirology
Volume314
Issue number1
DOIs
StatePublished - Sep 15 2003

Keywords

  • CD40
  • HIV-1 latency
  • Macrophages
  • Reactivation

ASJC Scopus subject areas

  • Virology

Fingerprint Dive into the research topics of 'CD154-CD40-induced reactivation of latent HIV-1 infection'. Together they form a unique fingerprint.

  • Cite this

    Kutsch, O., Levy, D. N., Kosloff, B. R., Shaw, G. M., & Benveniste, E. N. (2003). CD154-CD40-induced reactivation of latent HIV-1 infection. Virology, 314(1), 261-270. https://doi.org/10.1016/S0042-6822(03)00413-6