Disulfiram reactivates latent HIV-1 in a Bcl-2-transduced primary CD4+ T cell model without inducing global T cell activation

J Virol. 2011 Jun;85(12):6060-4. doi: 10.1128/JVI.02033-10. Epub 2011 Apr 6.

Abstract

Highly active antiretroviral therapy (HAART) can reduce plasma HIV-1 levels to below the detection limit. However, due to the latent reservoir in resting CD4(+) cells, HAART is not curative. Elimination of this reservoir is critical to curing HIV-1 infection. Agents that reactivate latent HIV-1 through nonspecific T cell activation are toxic. Here we demonstrate in a primary CD4(+) T cell model that the FDA-approved drug disulfiram reactivates latent HIV-1 without global T cell activation. The extent to which disulfiram reactivates latent HIV-1 in patient cells is unclear, but the drug alone or in combination may be useful in future eradication strategies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / therapeutic use
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / virology*
  • Cells, Cultured
  • Disulfiram / pharmacology*
  • Disulfiram / therapeutic use
  • Genes, bcl-2
  • HIV Infections / drug therapy
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HIV-1 / immunology
  • HIV-1 / physiology
  • Humans
  • Lymphocyte Activation / drug effects*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Transduction, Genetic
  • Virus Activation / drug effects*
  • Virus Latency / drug effects*

Substances

  • Anti-HIV Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Disulfiram