Polyamides reveal a role for repression in latency within resting T cells of HIV-infected donors

J Infect Dis. 2004 Oct 15;190(8):1429-37. doi: 10.1086/423822. Epub 2004 Sep 15.


Background: The persistence of human immunodeficiency virus (HIV) type 1 within resting CD4+ T cells poses a daunting therapeutic challenge. Histone deacetylase (HDAC)-1, a chromatin-remodeling enzyme that can mediate gene silencing, is recruited to the HIV-1 long terminal repeat by the host transcription factor LSF. Pyrrole-imidazole polyamides, small molecules that target specific DNA sequences, can access the nucleus of cells and specifically block transcription-factor binding.

Methods: We used polyamides to directly test the role of chromatin remodeling in HIV quiescence in primary resting CD4+ T cells obtained from HIV-infected patients.

Results: After exposure to any of 4 different polyamides that specifically block HDAC-1 recruitment by LSF to the HIV promoter, replication-competent HIV was recovered from cultures of resting CD4+ T cells in 6 of 8 HIV-infected patients whose viremia had been suppressed by therapy. In comparison, HIV was not recovered after exposure to control, mismatched polyamides but was recovered from 7 of 8 of these patients' samples after the activation of T cells.

Conclusions: We identify histone deacetylation as a mechanism that can dampen viral expression in infected, activated CD4+ T cells and establish a persistent, quiescent reservoir of HIV infection.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-HIV Agents / pharmacology
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / virology
  • Cells, Cultured
  • Enzyme Inhibitors / pharmacology
  • HIV Core Protein p24 / analysis
  • HIV Infections / virology*
  • HIV Long Terminal Repeat
  • HIV-1 / drug effects*
  • HIV-1 / immunology
  • HIV-1 / isolation & purification
  • Histone Deacetylases / metabolism
  • Humans
  • Imidazoles / pharmacology
  • Nylons / pharmacology*
  • Pyrroles / pharmacology
  • RNA, Viral / analysis
  • Virus Latency / drug effects*


  • Anti-HIV Agents
  • Enzyme Inhibitors
  • HIV Core Protein p24
  • Imidazoles
  • Nylons
  • Pyrroles
  • RNA, Viral
  • imidazole
  • Histone Deacetylases