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FEBS Lett. 2011 Apr 6;585(7):1103-11. doi: 10.1016/j.febslet.2011.03.017. Epub 2011 Mar 12.

Novel histone deacetylase inhibitor NCH-51 activates latent HIV-1 gene expression.

Author information

1
Department of Molecular and Cellular Biology, Nagoya City University Graduate School for Medical Sciences, Nagoya, Aichi, Japan.

Abstract

Pharmacological manipulations to purge human immunodeficiency virus (HIV) from latent reservoirs have been considered as an adjuvant therapeutic approach to highly-active antiretroviral therapy for the eradication of HIV. Our novel histone deacetylase inhibitor NCH-51 induced expression of latent HIV-1 with minimal cytotoxicity. Using chromatin immunoprecipitation assays, we observed a reduction of HDAC1 occupancy, histone hyperacetylation and the recruitment of positive transcription factors at the HIV-1 promoter in latently infected-cells under the treatment with NCH-51. Mutation studies of the long terminal repeat (LTR) revealed NCH-51 mediated gene expression through the Sp1 sites. When Sp1 expression was knocked-down by small interfering RNA, the NCH-51-mediated activation of a stably integrated HIV-1 LTR was attenuated. Moreover, the Sp1 inhibitor mithramycin A abolished the effects of NCH-51.

PMID:
21402072
DOI:
10.1016/j.febslet.2011.03.017
[Indexed for MEDLINE]
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