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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

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

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.[1]

References

  1. Polyamides reveal a role for repression in latency within resting T cells of HIV-infected donors. Ylisastigui, L., Coull, J.J., Rucker, V.C., Melander, C., Bosch, R.J., Brodie, S.J., Corey, L., Sodora, D.L., Dervan, P.B., Margolis, D.M. J. Infect. Dis. (2004) [Pubmed]
 
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