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

Olaf Kutsch, David 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

Fingerprint

HIV Infections
HIV-1
Tumor Necrosis Factor-alpha
Macrophages
T-Lymphocytes
Tumor Necrosis Factor Receptors
Cell Line
Genes

Keywords

  • CD40
  • HIV-1 latency
  • Macrophages
  • Reactivation

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Kutsch, O., Levy, D., 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

CD154-CD40-induced reactivation of latent HIV-1 infection. / Kutsch, Olaf; Levy, David; Kosloff, Barry R.; Shaw, George M.; Benveniste, Etty N.

In: Virology, Vol. 314, No. 1, 15.09.2003, p. 261-270.

Research output: Contribution to journalArticle

Kutsch, O, Levy, D, Kosloff, BR, Shaw, GM & Benveniste, EN 2003, 'CD154-CD40-induced reactivation of latent HIV-1 infection', Virology, vol. 314, no. 1, pp. 261-270. https://doi.org/10.1016/S0042-6822(03)00413-6
Kutsch, Olaf ; Levy, David ; Kosloff, Barry R. ; Shaw, George M. ; Benveniste, Etty N. / CD154-CD40-induced reactivation of latent HIV-1 infection. In: Virology. 2003 ; Vol. 314, No. 1. pp. 261-270.
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