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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. Pyrroleimidazole 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 …